Explainer
Animals Can Work Together, and Here Are a Few Notable Examples
Research•8 min read
Explainer
A fraught regulatory environment and human stubbornness help explain the roadblocks.
Words by Marlena Williams
In a bustling laboratory at the Harvard Stem Cell Institute, hundreds of scientists are busy creating self-organizing, three-dimensional tissue cultures known as organoids out of stem cells. These tiny cell cultures, ranging in size from the width of a hair to five millimeters, are capable of replicating the complexity of real human organs. In practical terms, scientists can — and already are — replicating human kidneys, brains, lungs, intestines, stomachs and livers. The technology offers us a huge opportunity to shift the way we test drugs, foods and cosmetic products. Scaled up, organoids could also eliminate the need to use animals in research and testing. By replicating the complexity and specificity of human organs, organoids offer an accurate, cost-effective and humane alternative to using animal models, so why aren’t we using them?
Organoids aren’t the only promising alternative on the horizon. From organs-on-chips — 3D devices that look and function like human organs — to highly sophisticated computer modeling systems, there are more alternatives to animal testing today than ever before.
And yet laboratory animals remain the dominant means by which we test products, with more than 115 million animals tested annually, to develop new drugs and study both human and animal diseases. While animal testing has certainly helped to usher in many life-saving medical and scientific advancements over the years — including the discovery of penicillin and the development of the polio vaccine — it comes with its own unique set of limitations and concerns.
Animals respond differently to drugs and stimuli than humans, especially when confined in the highly artificial and stressful environment of a lab, and testing on animals often creates unreliable and hard-to-replicate results. About 90 percent of drugs fail once they reach the human clinical trial stage. There are a variety of reasons why this happens, researchers say, including the fact that medicines function differently in the cells of one of the most common lab animals, mice, as compared to humans.
Animal testing is also expensive. The estimated dollar costs to bring a drug to market could be as much as $1 billion, give or take, to more than $2 billion in total, and for cancer drugs, can take more than a decade to hit the market.
So why are we still using laboratory animals, especially when so many other promising alternatives exist? This remains an incredibly fraught and complicated question, one that has divided scientists, animal advocates and even most Americans, for centuries.
There is no one definitive type of animal testing. Animals are tested on in a wide variety of ways, in a wide variety of settings, for a wide variety of reasons.
Scientific and medical researchers use animals to develop new drugs and vaccines, study biological systems and to advance new surgical procedures and treatment methods. Many commercial industries use laboratory animals to test the safety of their cosmetics, household cleaners, food additives, pesticides, chemicals and other potentially harmful substances, either by conducting the tests themselves or by contracting with third party companies.
Laboratory animals are also used in the classroom, in the military and even in outer space.
While there is no definitive number of how many animals are used in total in research and testing, it is estimated that more than 50 million laboratory animals are used in the United States each year. Rats and mice make up 85-95% of animal research subjects here, but dogs, monkeys, rabbits, guinea pigs, fish and birds are also widely used across many industries.
Until the 1960s, there were no federal laws regulating animal research or setting standards for laboratory animal welfare. With no federal oversight, the animal testing world was a sort of wild west, where researchers obtained their animal subjects from questionable sources — like unlicensed dealers and overcrowded animal shelters — and held them in often deplorable facilities, conducting a variety of cruel and unnecessary experiments and procedures on them without anesthesia or other pain management interventions.
The Animal Welfare Act was passed in 1966, largely in response to a disturbing story of a Dalmatian named Pepper who was stolen from her family home in Pennsylvania by an unscrupulous dealer and sold to a hospital in New York, where she was experimented on, killed and then incinerated. Pepper’s story — along with a sensational Life magazine article on dog dealers titled “Concentration Camps for Dogs” — spurred the welfare act’s passage and ushered in long overdue welfare protections for laboratory animals, including minimum standards for humane care, a registration system for testing facilities and a clear ban on the use of stolen animals in experiments.
A strategy known as the 3 R’s — short for Replacement, Reduction, and Refinement — quickly became the guiding principles for humane animal experimentation in the twentieth century, and remain so to this day. The idea is to reduce the number of animals used in testing and improve animal welfare conditions as much as possible.
The Animal Welfare Act — amended in 1985 to make research facilities more accountable — and the Health Research Extension Act that followed were designed to minimize the pain and stress experienced by laboratory animals, not to completely eliminate their use or explore non-animal alternatives.
Legal scholar and animal ethicist Paul Locke argues that the “keys to the laboratory” remain firmly in the hands of researchers. These scientists have little oversight and only have to report the most egregious failures and abuses to federal authorities. What’s more, any researchers who want to treat animals more humanely are often hamstrung by institutional practice, career pressures and a general culture that views animal testing as a “necessary evil.”
Proponents of animal testing often argue that animal models are justified because the benefits to humans outweigh concerns about animal suffering. But as more testing alternatives emerge, the reasons for sticking with animals begin to dwindle. At this point, there are countless technological advancements that could make both human and animal subjects unnecessary.
But despite the promise of these non-animal models, many institutions and researchers cling to the status quo —in part out of a resistance to change, but also a lack of real investment in proven alternatives and political tensions within competing movements.
In 1933, one woman died and more than a dozen others were blinded after using a permanent mascara and eyebrow dye called Lash Lure, which contained an untested chemical derived from coal tar called p-phenylenediamine. Lash Lure caused painful blisters, abscesses and ulcers in and around the eyes of its unsuspecting consumers, some of whom were photographed and featured in a display at the 1933 Chicago World Fair that one journalist referred to as “The American Chamber of Horrors.”
Just a few years later, 107 people, mostly children, died after ingesting the anti-bacterial drug Elixir Sulfanilamide, which contained a sweet-tasting ingredient also found in antifreeze.
The public outcry following the Lash Lure and Elixir Sulfanilamide tragedies prompted Congress to pass the Food, Drug and Cosmetic Act in 1938, the first law in the country to regulate the steadily growing pharmaceutical and cosmetics industries. The FDCA required cosmetics manufacturers to submit evidence of a product’s safety and effectiveness before marketing it to the general public. Animal testing quickly became the default way for cosmetics companies to ensure the safety of their products and to potentially avoid criminal liability for placing a harmful product on the market. Though the original FDCA didn’t require animal testing for cosmetics like it did for drugs, the agency still highly encouraged companies to test their products on animals.
One of the most common cosmetics testing methods involved “acute ocular toxicity,” or Draize, tests, named after the FDA scientist who invented the method in the 1940s. These tests involved restraining a conscious, unanesthetized rabbit and applying the chemical or product directly to its eyes. The substance was left on the eyeball for a set period of time, and the animal was then monitored for up to 14 days for signs of redness, swelling, hemorrhaging or irritation.
Draize tests remained the gold standard for FDCA compliance until a highly visible campaign, led by activist Henry Spira, drew attention to the tests in the 1980s. Spira ran an ad in the New York Times showing a blind laboratory bunny beneath the headline, “How many rabbits does Revlon blind for beauty’s sake?” The ad and resulting campaign brought increased attention to the cruelty of animal testing and prompted many brands to start searching for alternatives.
But cosmetics testing remains common, even in the 21st century. When companies choose to develop or use new ingredients in their products, they may still decide to conduct tests on animals to assess the safety of the product. No one wants to be responsible for another Lash Lure tragedy. Such tests, however, are now completely unnecessary: the FDCA does not explicitly require animal testing for cosmetics — only clearly demonstrated safety — and there are already thousands of ingredients available that have proven histories of safe and effective use.
By far the biggest factor keeping companies from going fully cruelty-free is China, which long required all cosmetics that entered its borders to be tested on animals. Though China has recently amended its regulations to exempt some imported products from mandatory testing, the country still requires animal testing for many popular cosmetics. Beauty companies that want to sell into the massive Chinese market–which accounted for a whopping $88 billion dollar sales in 2021 alone—must allow their products to be tested on animals.
While many cosmetics companies have decided to maintain their cruelty-free status and not sell or market their products in China, some of the biggest beauty companies like Revlon and L’Oreal, which in turn own dozens of other smaller beauty companies, do sell there. Though these companies will often adamantly deny using animal testing, they often do allow animal testing when required by law, likely meaning in China.
But the law elsewhere in the world is rapidly changing. The European Union banned cosmetics testing in 2013, and dozens of other countries, including Mexico, Canada, Australia and India, quickly followed suit. Though there is currently no federal law in the United States banning cosmetics testing outright, twelve U.S states prohibit the sale of products tested on animals within their borders.
Voters and consumers are understandably horrified by the idea of rubbing hairspray or perfume into the eyes of helpless white rabbits just so we can defrizz our hair or smell a little better. But making political and social progress on other forms of animal testing is a far more difficult task. When it comes to toxicity testing, progress towards alternative methods has long been delayed by an often surprising web of conflicts between environmentalists, animal advocates, government agencies and polluting corporations.
Take, for example, the case of the Environmental Protection Agency. In September 2019, Andrew Wheeler, the head of the EPA under Donald Trump, announced that the agency would reduce animal toxicity tests by 30 percent by 2025 and stop these experiments altogether by 2035.
Under the Toxic Substances Control Act, the EPA is empowered to conduct and oversee a massive amount of animal testing — involving anywhere from 20,000 to 100,000 animals annually —in order to determine the effects of certain chemicals or pollutants on fertility, development, genetics and overall health. These tests often involve pumping chemicals straight into an animal’s stomach or forcing animals to inhale potentially lethal chemicals in a gas chamber.
The Food, Drug and Cosmetics Act further authorizes the EPA to regulate pesticides. When registering a new pesticide, the EPA requires companies to perform a 90-day oral toxicity study on both rodent and non-rodent species — typically cats and dogs —as part of its human health risk assessment. A 2019 undercover investigation by the Humane Society of the United States revealed dozens of beagles being force-fed varying doses of pesticides at a Dow AgroSciences facility in order to test their toxicity as required by the EPA.
But Wheeler’s decision to roll back animal testing requirements was immediately criticized by people within the environmental movement, who accused the administrator of bowing to pressure from the powerful chemical industry. Chemical giants like Dow and DuPont tend to balk at such testing because it is both time-consuming and expensive.
While Wheeler maintained that his decision was based out of his love for animals, it wasn’t a logical jump to assume that the Trump administration was favoring polluting industries over the health of American citizens and the environment. Major environmental groups like the National Resources Defense Counsel have since come out in support of animal toxicity tests.
These debates show the political thorniness of the toxicity testing debate, which pits environmental groups against the agency tasked with protecting the environment, and aligns animal advocates with the conservatives and big businesses they often oppose.
While animal toxicity tests may prevent potentially dangerous chemicals from harming people, other animals and the environment, these tests are less fool-proof than the agency’s reliance on them might suggest. One study found oral toxicity testing on dogs to be an unnecessary step, and another showed that rodent models accurately predicted human toxicity in only 43 percent of cases. Lethal dose tests, whereby animals are forced to swallow large amounts of chemicals to determine the amount that causes death, are considered impractical, as most humans are exposed to these harmful substances at far slower rates and in far smaller doses.
The National Academy of the Sciences has been urging a shift away from animal testing since 2007. Thanks to a grant from the EPA, scientists at Johns Hopkins have been working to develop lab grown “mini-brains” that may enable researchers to study neurotoxic effects without the need for animal subjects. Even simple changes, like improving the searchability of the EPA’s current testing data, could dramatically reduce the need to test chemicals and pesticides on animals.
But in another twist, it now seems that under the Biden administration, the EPA has scrapped its plans to eliminate animal testing, instead opting for the vague goal of reducing reliance on animal models and researching viable alternatives.
New non-animal models will require rigorous regulatory approval before they are accepted, and even proponents of these alternatives think they are still a long way off from becoming the norm. A potent mix of government inertia, political volatility and public skepticism towards new methods may favor the status quo over more humane and effective alternatives.
The toxicity debates look tame compared to the contentious, often ugly debates that have been raging between animal advocates and the medical and scientific community since at least the 19th century.
Professor Paul Locke calls this the “cures vs. creatures” dilemma. On the one hand, there is deep societal respect and need for the doctors and scientists who rely on animal models to better understand human biology, cure horrible diseases and prevent future harms.
But on the other hand, there is an equally strong societal force that believes animals are sentient creatures deserving of protections and rights. Animal advocates find something deeply hypocritical about a research model that uses animal subjects because of their similarity to humans while refusing to acknowledge that these creatures are capable of many of the same emotions and sensations as us.
“To avoid seeing this double treatment as a problem, and thus to avoid ethical reflection on it, requires an extraordinary level of self-deception, rationalization, and selective blindness,” writes scientist John Gluck in his book, Voracious Science and Vulnerable Animals. “It requires [researchers] to objectify experimental animals, categorically excluding them from the class of beings requiring full ethical considerations.”
Both sides of the “cures vs. creatures” dilemma deploy rousing narratives and imagery to prove the nobility of their cause. Animal activists can shock and horrify with nightmarish stories about the thousands of dogs, cats, monkeys and rodents who suffer in labs, while doctors and researchers can comfort and inspire with stories of the life-saving medical advancements that have benefited from animal testing, from the cure for smallpox to the COVID-19 vaccine. But these competing narratives can help to keep the animal testing debate polarized and forestall any effective progress towards widely available non-animal alternatives that could both eliminate animal suffering and offer more accurate, reliable and cost-effective results.
Scholars and animal advocates like Paul Locke believe that animal models will be needed as medical and scientific tools until enough money is pumped into the system to support and vet non-animal alternatives. While technologies like organoids, organs-on-chips and computer simulations show great promise for future advancements, there has not been enough institutional interest or investment in these alternatives to make a meaningful difference in transforming the current system.
In 2023, President Biden signed into law an amendment to the FDCA removing the requirement that pharmaceutical companies test their drugs on animals before moving on to human clinical trials. Testing is no longer required, but it may still be encouraged by the agency if they believe it is useful or necessary. Last year’s federal budget also included $5 million dollars for a new FDA program designed to develop and encourage non-animal testing methods.
But $5 million dollars is a mere drop in the bucket of the FDA’s massive $8.4 billion federal budget and is hardly enough to support the large-scale institutional shift that will be necessary to replace animal testing with non-animal alternatives. If the National Institute of Health invested just 1 percent of its whopping $48 billion dollar budget in exploring non-animal alternatives, for example, we could make significant progress towards shifting away from animal testing, at least when it comes to scientific and medical research.
Laboratory animals receive certain minimal welfare protections under the law, but they continue to be used by the millions for research testing for a wide range of industries — from food to fashion to biomedical research — despite the alternatives.
For researchers to shift to using these new methods, we may just need to, as scientist John Gluck writes, “rethink and re-form the entire framework of beliefs that underlies our relationship with nonhuman species.” But that kind of rethinking will require a serious national conversation about the place of animals in society, and how they should be treated and perceived, in the laboratory and beyond.