Computer models may soon replace some animal subjects. A research chimpanzee being prepared for a sanctuary. [Melissa Golden for The New York Times]
In 1937, an American drug company introduced an elixir to treat strep throat – and unwittingly set off a public health disaster. The product, which had not been tested in humans or animals, contained a solvent that turned out to be toxic. More than 100 people died.
The following year, the US Congress passed the Federal Food, Drug and Cosmetic Safety Act, requiring pharmaceutical companies to submit safety data to the US Food and Drug Administration before selling new medications, helping to usher in an era of animal toxicity testing.
Now, a new chapter in drug development may be beginning. The FDA Modernization Act 2.0, signed into law late last year, allows drug makers to collect initial safety and efficacy data using high-tech new tools instead of animals. Other countries are making similar shifts. In 2021, the European Parliament called for a plan to phase out animal testing.
These moves have been driven by a confluence of factors, including evolving views of animals and a desire to make drug development cheaper and faster, experts said. But what is finally making them feasible is the development of sophisticated alternatives to animal testing.
Many of these technologies need to be refined, standardized and validated before they can be used routinely. But momentum is building for non-animal approaches, which could ultimately speed drug development, improve patient outcomes and reduce burdens on lab animals.
“Animals are simply a surrogate for predicting what’s going to happen in a human,” said Nicole Kleinstreuer, director of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods. “If we can get to a place where we actually have a fully human-relevant model, then we don’t need the black box of animals anymore.”
Animal rights groups have been lobbying for a reduction in animal testing for decades. In a 2022 Gallup poll, 43 percent of Americans said that medical testing on animals was “morally wrong,” up from 26 percent in 2001.
Animal testing is also time-consuming, expensive and vulnerable to shortages. Many medications that appear promising in animals do not work in humans.
“We’re not 70-kilogram rats,” said Dr Thomas Hartung, who directs the Johns Hopkins Center for Alternatives to Animal Testing in Maryland. “There’s a lot of pressure, not just for ethical reasons, but also for these economical reasons and for really closing safety gaps, to adapt to things which are more modern and human relevant.”
In recent years, scientists have coaxed human stem cells to assemble themselves into a small, three-dimensional clump, known as an organoid, that displays some of the same basic traits as a specific human organ, such as a brain, a lung or a kidney. Scientists can use these mini-organs to test treatments.
Another approach relies on “organs on a chip.” These devices contain tiny channels that can be lined with different kinds of human cells. Researchers can pump drugs through the channels to simulate how they might travel through a part of the body.
There are also computational models that can predict whether a compound is likely to be toxic and how quickly it will be metabolized.
For now, these alternative methods are better at predicting relatively simple, short-term outcomes, such as acute toxicity, than complicated, long-term ones, such as whether a chemical might increase the risk of cancer when used over months or years, scientists said.
Nicole zur Nieden, a developmental toxicologist at the University of California, Riverside, said the new approaches could help screen out ineffective and unsafe compounds before they get to animal trials. That would reduce the number of animal studies researchers need to conduct and limit the chemicals lab animals are exposed to, she said, adding, “we will be able to reduce the suffering of test animals quite tremendously.”
This article originally appeared in The New York Times.