The Covid-19 crisis highlights some economic and welfare issues involving the use of animals for research. Pandemic-related closures mean many labs have to halt experiments and culling animals. At that time, the race to develop vaccines and treatments for Covid-19 meant that Monkey was offered short due to great demand.
Although alternative methods are promising, they are relatively new. Methods for developing organ chips, organoids, and computer models also vary between laboratories, making it difficult to draw general conclusions about their accuracy.
The Boston biotech company’s Emulate chip, co-founded by Ingber, is testing how well its liver-on-chip device works at flagging the presence of dangerous chemicals. Lorna Ewart, the company’s chief scientific officer, said hepatotoxicity was the main reason why clinical drug trials were stopped or products withdrawn from the market after approval. Animal models may not be an accurate predictor of liver toxicity in humans, she said, because animals metabolize drugs differently than humans.
Simulation scientists recently performed a blind test on the company’s liver chip of 27 drugs, some known to be hepatotoxic and some safe. They found that the chip correctly identified 87% of the drugs that caused liver damage in patients and did not misidentify any of the drugs as toxic. Ewart said previous animal tests, used for comparison, did not always predict safety problems. “In some cases, the animal models do not adequately inform the investigator of the true outcome,” she said. research is published in a magazine natural communication in December.
But organs on a chip have their limitations. First, they are not ideal for testing certain drugs and compounds, especially those with low molecular weight, which tend to absorb into the rubber polymer channels of the chip. That’s a problem, Ewart says, because if the drug gets stuck in the plastic and doesn’t actually come into contact with the cells inside, it will skew the test results. And organs on a chip often require special instrumentation to conduct testing and read data.
“I don’t think organ-on-chip will do it all. I think we’re going to need a bunch of different, complementary tests,” said Jeffrey Morgan, a professor of engineering and director of the Center for Animal Alternative Experimentation at Brown University. He says organ chips tend to be better for shorter, one- or two-week trials, but longer-term testing is an unmet need. For example, in some cases, chronic toxicity of a drug or chemical occurs only after long-term exposure, sometimes at low doses. Good alternative testing methods that reproduce this kind of scenario do not exist, he said.
And while techniques for growing organics have advanced dramatically 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 need to thoroughly examine any new methods used on behalf of animals. In an emailed statement, an agency spokesperson wrote that the new law does not change the regulatory process for the drug: “The FDA will continue to ensure that clinical investigations of the drug are reasonably safe to use. primary use in humans.” The spending bill passed in late 2022 also includes $5 million for an affiliate program for the purpose of evaluating alternative methods.
And it’s possible that different methods are useful for testing different drugs or monitoring for certain side effects. “They have to be proven to be relevant, reliable, and truly predictive of the endpoints they are evaluating,” says Locke. “It’s going to be a scientific challenge, and it’s going to take some time to do that.”
