How Animal Testing Works

in #science • 7 years ago

 Russian scientists prepare a monkey for space-medicine-related testing. 

 Sulfanilamide is amazing stuff. At least, in the early 20th century it was.

An antibiotic, sulfanilamide was a highly effective treatment for all kinds of infections. Typically, people took it in the form of a powder. But in 1937, Tennessee-based pharmaceutical company S.E. Massengill learned of a demand for the drug in liquid form. The company's head chemist, Harold Cole Watkins, went to work in his lab and discovered that sulfanilamide dissolved nicely into a solution of diethylene glycol. The control lab stirred in a delicious raspberry flavoring, tested it out for taste, looks, and smell and gave it a thumbs up. They called it Elixir Sulfanilamide. A short time later S.E. Massengill was churning out a huge batch of the stuff. In September they sent 633 shipments to all corners of the country. 

 But then, on Oct. 11, doctors in Tulsa, Oklahoma, contacted the American Medical Association (AMA) to report their suspicions that this fancy new elixir wasn't curing people — it was killing them. The AMA got its hands on a sample and tested it. The sulfanilamide was fine; that wasn't the problem. The problem was the diethylene glycol, which happened to be pure poison. Not the kind of poison that makes you feel ill for a few hours; the kind of poison that makes you scream and writhe in agony as you die.

The Food and Drug Administration swung into action, firing up a national public awareness campaign and sending inspectors far and wide to locate and account for every single drop of the fatal fluid that had killed more than 100 people in 15 states.

At this point, contemporary readers shake their collective heads in amazement and wonder, how? How is this possible? How could a drug company think a fatal poison would be a good medium for an antibiotic? Clearly Watkins hadn't done his homework. There were existing studies that revealed the damage diethylene glycol could do. He hadn't read them. Fine, mistakes happen. That's why we create fail-safe measures. That's why we test things, especially drugs.

Ah, but there's the rub. Remember, the only tests S.E. Massengill conducted on the elixir were for taste, smell and appearance. They didn't bother testing to see whether it happened to kill people. Why? They didn't have to.

In fact, the president of the company infamously parried accusations by pointing out that while the incident was unfortunate, S.E. Massengill had done nothing wrong. Watkins seems to have disagreed by promptly taking his own life [source: Ballentine].

In 1938 the U.S. Congress enacted the Federal Food, Drug and Cosmetic Act, which, among other things, required all new drugs be subjected to animal testing before being approved for sale. 

 In second-century Rome, the legendary Greek medical specialist Galen was about to conduct a public demonstration of one of his extraordinary findings. In a hall rented for the purpose, a squealing pig was strapped down as Galen explained to the assembled intelligentsia how he was going to show them that animals had something called nerves that controlled everything, right down to the voice. With a small nick of the appropriate nerves, he claimed, he could silence the pig without otherwise harming it.

But before he could begin the procedure, a noted philosopher named Alexander Damascenus objected that, even if the pig stopped squealing, it wouldn't prove that humans had a comparable nervous system. And in any case, said Damascenus, demonstrations were pointless. Galen's claim couldn't be true. 

 This was what Galen and anybody else who practiced the scientific method were up against. Ancient Greek and Roman philosophy held that seeing was not necessarily believing. Empirical evidence did not trump logic or established opinion. Aristotle held that the heart, not the brain, controlled all thinking and speaking, and for many philosophers of the time, Aristotle's word was law. Nicking a pig wasn't going to change Damascenus's mind about that.

Galen stormed out, declaring he wasn't about to waste his time with know-nothing boneheads (or words to that effect). His audience quickly condemned Damascenus and begged Galen to follow through with the experiment, and Galen obliged. The squealing pig demonstration astounded its witnesses and is one of the first recorded instances of animal experimentation conducted in the interests of science [source: Gross].

Actually, long before Galen, in the fourth century B.C.E., Aristotle had performed some live-animal testing as well, with imperfect results. And not long after, another early Greek physician by the name of Erasistratus tried his hand at animal experimentation.

In Moorish Spain in the 12th century, the Arab physician Ibn Zuhr, also known as Avenzoar, tried out some of his innovative surgical techniques on animals before applying them to humans [source: Hajar]. Of course, this was long before the benefits of anesthesia, so both the animals and the humans had a rough time of it.

In the 19th century, the French physiologist Claude Bernard (considered by many to be the father of physiology) was so effective a promoter of animal testing that he made it integral to the modern scientific method. While many people felt, like Damascenus, that the physiology of pigs and other animals had nothing to do with humans, Bernard was able to show that vertebrate mammals were actually very similar to people. Similar enough, he said, to make animal testing highly valuable in the ongoing effort to improve human health [source: Hajar]. And human health needed a lot of improving.

A harrowing chapter in the "Little House on the Prairie" book series describes the near annihilation of the Ingalls family by malaria after a plague of mosquitoes besieged them. In the 1870s, when people like the Ingallses were settling the Midwestern U.S., common opinion blamed everything from "damp air" to watermelons for the disease. Nobody had any idea that tiny blood-borne bacteria carried by mosquitoes were the killers.

Then, in the late 19th century, German microbiologist Robert Koch got some blood samples from cows killed by anthrax. Under the microscope he noted some unusual looking bacteria that he theorized might be the disease itself. The only way to know for sure was to take some of that cow blood and inject it into mice. Sure enough, the mice soon had anthrax, too. This was revolutionary, and it paved the way for Louis Pasteur's formulation of the theory that germs could cause disease [source: NAP].

Animal testing had proven its value in the area of research. A few decades later, the Elixir Sulfanilamide disaster would make it a mandatory element of all drug development. 

 

In 1957, the Russian geneticist Dmitry K. Belyaev had a plan. He wanted to see whether he could duplicate the domestication of dogs in another species. It had taken humans thousands of years to tame dogs through selective breeding. Could Belyaev accomplish the same thing with foxes in a single human lifetime?

He went to Siberia, rounded up some silver foxes bred for the fur trade and began the experiment. Every time a litter was born, he would subject the little fox kits to a standard test of tameness. The calmest, gentlest kits were selected and the rest killed. After 25 years and 20 generations of foxes, the experiment succeeded in breeding foxes that were tame enough to be pets. Interestingly, as the foxes became tamer, their tails shortened and began to curl, their ears got floppier and their coats became spottier. This parallel shift in physical traits along with behavioral traits is known as domestication syndrome, and investigating that process has led to insights into evolutionary development [source: Newman and Craig].

 The silver fox experiment is an example of animal testing used in behavioral research. Pavlov's famous dogs fall under this category as well. But these are just a few instances of the manifold ways in which scientists use animals to help them answer a wide range of questions.

Much research in the field of evolutionary biology is conducted using fruit flies and tiny nematode worms, thanks to their rapid rates of reproduction and ease of breeding. Researchers sometimes use nematodes like C. elegans, for instance, to identify an effective antibiotic by infecting a group of worms with a disease, then exposing a control group to a potential antibiotic to see who survives [source: AnimalResearch.Info].

In the area of disease research, it all depends on which animals are susceptible to what. Armadillos, for instance, are the only creatures other than humans known to suffer from leprosy, also known as Hansen's disease. Just like Goldilocks' favorite porridge, their body temperature is justright to allow them to harbor the M. leprae bacteria. As a result, scientists used those armored critters to better understand leprosy and create an experimental vaccine [source: AnimalResearch.Info].

Famously, rats are common denizens of laboratories, but mice are even more ubiquitous thanks to the fact that their genes and ours overlap by a whopping 90 percent, not to mention the fact that their cell structure and organ organization are essentially the same as ours. Much of the research conducted with mice consists of breeding and genetic modification together with behavioral experiments, which often involve memory tests and mazes.

Cats are typically used for neurological research into diseases, treatments and general function because of their highly developed senses of hearing, sight and balance. Dogs, especially the docile beagle, are the subjects of biomedical research into conditions like prostate cancer and muscular dystrophy since they are the only other species to share these diseases with us [source: AnimalResearch.Info]. They're also often the second step in the process of testing drugs for safety. In certain cases, after researchers try a drug out on mice, they'll proceed to dogs.

Then, of course, there are the non-human primates (mostly macaque monkeys because of their large and widely distributed population). While the number of experiments with primates have gone down drastically in recent decades (more on that later), neuroscientists looking into brain diseases such as Alzheimer's still rely on them for advances in that field. That's because there are just no other animals that have brains as similar to humans as those distant, simian cousins [source: Oxford University].

Labelling

Product labels like to boast that the contents of their containers have been created without testing any animals. The only problem is that there are no rules regulating the use of such reassuring phrases as "cruelty-free" or "not tested on animals." That means that a cosmetics company, for instance, could refrain from testing its final product on animals but rely on suppliers to do the dirty work on the raw ingredients. Also, since many raw ingredients have been tested on animals in the past, manufacturers don't need to retest them [source: FDA]. So in that case, the labeling should really read, "Not tested on animals ... recently."

 

Every year of the 20th century saw human life expectancy go up by roughly three months. Advocates of animal testing argue that this near-miraculous life extension is thanks, in part, to animal experimentation. Modern medicine as we know it, they point out, would be impossible without it. From antibiotics and vaccines to surgeries and cancer treatments, every major advance has involved experimenting on animals. For that reason, those in favor of animal testing argue that the practice must continue in order to further the goals of medical advancement. After all, they say, more than 50 percent of human illnesses extant in the world today still have no known treatment [source: Oxford University].

Many disagree. In the anti-animal testing camp, organizations like People for the Ethical Treatment of Animals (PETA) say that experimenting on living beings that cannot consent to the process is unethical, harmful and wasteful. They point to the suffering endured by many of the animals used in scientific research and contend that this suffering is, in fact, needless.

The argument goes something like this: While researchers have been able to cure cancer in mice for years, the treatments used have never translated to humans. The same goes for the 85 HIV/AIDS vaccines successfully tested on primates. In fact, one such vaccine might have actually made people more, rather than less, prone to contracting the disease. Even the U.S. Food and Drug Administration has admitted that nine-tenths of all drugs in development fail in humans during early testing phases because animal experimentation can't accurately predict how well they work on us [source: PETA].

Meanwhile, the general consensus in the scientific community is that animal testing remains both useful and necessary. Ultimately there is no substitute, they argue, for the complex variables to be found in a living creature. Because we still do not fully understand all of the elements that make up a complex organism, it's impossible to predict how a drug, for instance, will interact with the various systems that animate bodies. 

 

For nearly as long as researchers have been using animals in scientific experiments, a debate has raged over the ethics of the practice. No less an authority than Charles Darwin himself waded into the controversy. Darwin believed passionately in the study of animal physiology, but he was equally driven to support the humane treatment of animals.

In 1874 four scientists were put on trial for torturing dogs during a demonstration in which the animals were cut open and infused with alcohol and absinthe to test the substances' effects on the nervous system, all without the benefit of anesthesia. The accused were acquitted, but the case was one of several that brought the issue of animal testing into the spotlight. 

While some called for the outright ban of animal testing (or vivisection, as it was then called) Darwin began working with other, more moderate campaigners in the U.K. to craft a bill that would tightly regulate the practice. Believing that scientists could experiment with animals humanely, Darwin poured energy into what would become known as the Cruelty to Animals Act of 1876 [source: Johnson].

Regulation of animal testing has continued to be refined in the years since. In 1954 an organization called the Universities Federation of Animal Welfare decided to sponsor promising young zoologist/psychologist William Russell and Rex Burch, a microbiologist, in their efforts to look into the state of animal testing.

The report Russell and Burch produced in 1959 introduced a concept that has since become integral to the humane practice of animal testing. The concept is known as the 3Rs: replacement, reduction and refinement. The idea is that before conducting an experiment, researchers should seek to replace sentient creatures with non-sentient ones; where replacement is impossible, they should try to reduce the number of animals used to an absolute minimum; and finally scientists must refine their experimentation techniques to reduce the animals' suffering as much as possible [source: Flecknell]. The 3Rs are a simple way of articulating the regulations and requirements in the Animal Welfare Act. Researchers tend to adhere to these principles not only because they're humane, but also because they encourage better science.

If animal-rights advocates and pro-animal testing scientists can agree on one thing, it's the 3Rs. But organizations like PETA contend that much more should be done to replace, reduce and refine testing. They cite studies that demonstrate the superiority of alternative testing techniques. They say researchers should focus on using human volunteers, sophisticated computer modeling, and in-vitro human cells and tissues, which, they argue, have been shown to produce more accurate results than animal testing.

Those who support continued use of animals in testing argue that while alternative testing procedures are highly valuable, they haven't yet replaced every process. In certain cases, in-vitro testing and computer modeling can't be substituted for real bodies [source: Oxford University].

The debate rages on, and public opinion appears to be split on the issue of whether animals should be used for research [source: Pew]. Pressure from animal advocacy groups, together with the application of the 3Rs, has resulted in the steady decline in the use of certain animals for testing, particularly primates [source: Oxford University].

Those who feel that animals should be humanely treated, but simultaneously fear that banning animal testing could slow the pace of scientific advancement, are left with a quandary. Ultimately, to condone animal testing we must believe that human lives are more valuable than those of our non-human fellow earthlings. While such a belief is widely shared, it is a matter of bias, not fact. But we are biased creatures; there's no need to test the truth of that.

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Author's Note: How Animal Testing Works

In high school biology class I was one of those kids who opted out of chloroforming and dissecting a frog. I couldn't stomach it. My first instinct is to reject the idea of animal testing, but in researching this article it was hard to miss the fact that, were it not for the innumerable medical advances made possible by animal experimentation, I probably wouldn't be alive today. Is it inevitable that human health and longevity must be bought with the suffering and death of non-human animals? Perhaps in the 21st century, advanced testing methods eventually make this equation a relic of the past.

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