Breakthroughs Might Mean the End of Animal Testing

Depression research. Mice hanging by their tails from sensors during research on treatments for depression. Depressed mice become immobile, so their activity, as detected by the sensors, is a measure of the effectiveness of treatments for depression. This work is being carried out at the CNRS Institute of Molecular and Cellular Pharmacology (IPMC), Valbonne, France. Philippe Psaila/Science Source

Public support for animal testing has been in steady decline since the 1950s, dropping from above 90 percent in 1949 to only 57 percent in 2013. And that number is likely to fall even further, with younger demographics opposing animal experimentation in even greater numbers than previous generations.

For many laboratory scientists, this waning approval isn't cause for concern, because a near-identical trend is emerging within the research community, and more and more U.S. labs are using innovative cross-disciplinary technologies to spare at least some of the 25 million animals used for research annually.

But while compassion and ethics are indeed factors, the new paradigm is actually driven by a striving for improvement that is a hallmark of the best science. In 2014, the limitations of animal testing appear to have caught up with research and development, leading many to question whether the practice is still relevant.

The most obvious problem is the fundamental biological difference between humans and the animals used in research. The inner workings of rat and human may be similar, but they are by no means identical. When it comes to drug discovery and development, these limitations can jeopardize every segment of the pharmaceutical pipeline, from synthesis to prescription. Side effects are missed, and millions of dollars are wasted. Even if a new chemical entity is deemed safe at the animal stage, it still only has an 8 percent chance of being approved for human use.

That doesn't mean animal testing doesn't work—in fact, the Food and Drug Administration mandates its use in virtually all drug review processes. Pick any drug you've heard of; it was probably tested on a rat. But there is significant room for improvement.

A move away from animal testing will require some lateral thinking: Life must become a little more abstract. An example of this is called in silico modelling. It sounds complex, but it's really just a fancy term for computer simulation. After centuries of scholarship and decades of technological breakthroughs in computation, many biological reactions can now be emulated and predicted with sophisticated algorithms. "Advanced computer-modeling techniques can be used instead of animals in disease research, drug development and chemical testing," Amy Clippinger, a cellular and molecular biologist who currently works with PETA, tells Newsweek. "Computer models...have saved millions of animals from suffering in toxicity testing experiments."

But machines will never be able to do everything a rat can. One of the more pressing issues is metabolite profiling, where researchers try to figure out what exactly will happen to the body when it tries to process a given pharmaceutical. After a chemical agent is ingested, it ultimately reacts with the liver, giving rise to a myriad of so-called metabolites—some of which are toxic. Metabolic profiling is aimed at spotting these bad seeds and removing them.

For a long time, animal testing has been the only way to derive these profiles. But these experiments are far from perfect, because they rarely yield a complete picture of all potential byproducts. Metabolites that are highly water-soluble, for example, are easy to miss, as they quickly disappear in conventional solvents. As a result, chemists are left relying on a process that veers uncomfortably close to guesswork.

"It's not the easiest job for a chemist to isolate these metabolites from biological fluids," Mukund Chorghade, a veteran chemist who spent two and a half decades in the pharmaceutical industry, tells Newsweek. "You're left with very small quantities, and now the big challenge for you is to understand what you have in your hand."

Chorghade, who also serves as chief scientific officer of the clinical intelligence company Empiriko, has spent the latter half of his life searching for a way to refine this investigative process in order to make it less dependent on animals. Last year, he broke through. "The idea was very simple: First of all, we started with liver cells, which can generate these metabolic products," he explains. After months of development, he and his team found themselves with the chemical compound they now call the "chemosynthetic liver."

The innovation takes the place of animal mediums: Instead of running the drug through an animal liver, a chemist can now force the drug to react with the chemosynthetic liver. And while animal models give only the gist of the results, the chemosynthetic liver offers new clarity. "We can give you very accurate structural data—nothing is left to guess work," Chorghade explains. "We imagine a future where we're able to identify every possible metabolite."

In one sample trial, the chemosynthetic liver was able to catch a particularly nasty metabolite that would have set the developer back millions in dollars and countless hours of research. It did so by providing a level of specificity that would otherwise have required about 1,000 rats and 100 dogs.

Though still in its early phase, the method has already proven viable in 50 similar sample studies. That puts it halfway to FDA approval.

That project dovetails with a similar effort at Harvard's Wyss Institute, where researchers are currently developing "organs-on-chips"—microchips that can mimic the functions of vital organs. By suspending microfluidic channels of living human cells in clear polymer, the team is able to create tiny biological systems no bigger than a computer memory stick. "The pharmaceutical industry needs alternative ways to screen drug candidates in the laboratory," they write. "These microchips...could one day form an accurate alternative to traditional animal testing."

The proposed pipeline currently includes lung-on-a-chip, heart-on-a-chip, kidney-on-a-chip, and even brain-on-a-chip. The goal is to build 10 miniature systems and link them together, thereby mimicking whole-body physiology. A human-on-a-chip, if you will.

But even in light of these breakthroughs, few predict a definitive end to animal testing. The most progressive scientists will tell you animals are still indispensable in numerous areas of science, such as genetic engineering and the study of neurodegenerative disorders like Alzheimer's disease. Without animals, research in these fields would be nearly impossible.

Policymakers and scientific authorities are in agreement: U.S. research must do more to avoid and minimize animal testing. But the practice, they say, must reach a minimum-not a complete halt.