US just approved high-tech alternatives to animal testing

The Covid-19 crisis has highlighted certain economic and welfare issues associated with the use of animals for research. Pandemic-related closures have meant many labs have had to halt experiments and euthanize animals. Back then, the race to develop vaccines and treatments for Covid-19 meant monkeys were in short supply due to huge demand.

Although alternative methods are promising, they are still relatively new. Methods for developing organ chips, organoids, and computer models also vary from lab to lab, making general conclusions about their accuracy difficult.

Emulate, a Boston-based biotech company co-founded by Ingber, is testing how well its liver-on-a-chip device detects the presence of hazardous chemicals. Lorna Ewart, the company’s chief scientist, says liver toxicity is the main reason drug clinical trials are stopped or products are taken off the market after approval. Animal models may not be accurate predictors of liver toxicity in humans, she says, because they metabolize drugs differently than humans.

Emulate scientists recently ran a blind test on the company’s liver chip of 27 drugs, some of which are known to be toxic to the liver and some of which are safe. They found that the chip correctly identified 87 percent of drugs that cause liver damage in patients and did not identify any drugs as toxic. Ewart says previous animal tests used for comparison didn’t always predict safety issues. “In some cases, the animal models did not fully inform the researcher of the true outcome,” she says. The study was published in a magazine Connection with nature December.

But organs on chips have their limitations. First, they are not ideal for testing certain types of drugs and compounds, especially low molecular weight compounds that tend to be absorbed into the rubber polymer channels of the chip. Ewart says this is a problem because if the drug gets into the plastic and isn’t actually exposed to the cells inside, it will skew the test results. And organs on chips often require special tools to perform testing and read data.

“I don’t think the organ-on-a-chip will do all that. I think we’re going to need a number of different additional tests,” says Jeffrey Morgan, professor of engineering and director of the Center for Alternatives to Animal Testing at Brown University. He says organ chips are generally better for shorter tests, within a week or two, but long-term tests are an unmet need. For example, in some cases, chronic toxicity of a drug or chemical is only apparent after prolonged exposure, sometimes at low doses. According to him, there are no good alternative testing methods that reproduce such a scenario.

And although organoid design techniques have advanced significantly in recent years, the structures are still relatively simple. They do not have all the cell types or characteristics of real human organs, which may limit their reliability. Organoids also take months to grow in the lab.

For its part, the FDA will still need to scrutinize any new methods that are used instead of animals. In an emailed statement, a spokesman for the agency wrote that the new law does not change the drug regulatory process: “The FDA will continue to maintain reasonable safety for clinical trials of drugs for initial use in humans.” The spending bill, passed at the end of 2022, also includes $5 million for agent program purpose of evaluating alternative methods.

And it may happen that different methods are useful for testing different drugs or watching for certain side effects. “They have to be shown to be relevant and reliable and really predict the endpoints they evaluate,” says Locke. “It will be a scientific challenge and it will take time.”