The Covid-19 crisis has highlighted certain economic and welfare issues associated with using animals for research. Due to pandemic-related shutdowns, many laboratories have had to suspend experiments and euthanize animals. Then the race to develop a vaccine and cure for Covid-19 meant monkeys were in short supply due to huge demand.
Alternative methods are promising, but they are still relatively new. How organ chips, organoids, and computer models are developed also varies from lab to lab, making it difficult to draw broad conclusions about their accuracy.
Boston biotech company Chip Emulate, which Ingber co-founded, is testing how well its lever-on-chip device works at flagging the presence of dangerous chemicals. The company’s chief scientific officer, Lorna Ewart, says liver toxicity is the main reason clinical trials are stopped or products are withdrawn from the market after approval. Animal models may not accurately predict liver toxicity in humans because they metabolize drugs differently than humans, she said.
Emulating scientists recently conducted a blind test against the company’s 27 drug liver chips. Some of these drugs are known to be toxic to the liver, while others are safe. They found that the chip correctly identified 87% of the drugs that caused liver damage in patients, and falsely identified none as toxic. Ewart says previous animal studies used as comparisons did not necessarily predict safety issues. “In some cases, the animal model did not adequately convey the true results to researchers,” she says.The study was published in a journal Nature Communications in December.
However, organ-on-a-chip has limitations. For one thing, it’s not ideal for testing certain drugs and compounds, especially low-molecular-weight drugs and compounds that tend to be absorbed into the chip’s rubber-polymer channels. . Because if the drug gets stuck in the plastic and isn’t really exposed to the cells inside, it will skew the test results. Organ-on-a-chip also often requires special equipment to perform the tests and read the data.
“I don’t think the organ-on-a-chip will do it all. I think it will require a different and complementary set of tests,” said Jeffrey Matthews, professor of engineering and director of the Animal Substitution Testing Center for Testing at Brown University. says Morgan. According to him, organ chips tend to be suitable for short-term testing, he said, one to two weeks, but long-term testing is still unfulfilled. For example, chronic toxicity of drugs and chemicals may become apparent only after long-term exposure, sometimes at low doses. There is no good alternative test method to reproduce this kind of scenario, he says.
Also, although the techniques for developing organoids have advanced significantly in recent years, their structures are still relatively simple. They do not have all the cell types or characteristics of real human organs, which can limit their reliability. Organoids also take months to grow in the lab.
FDA should thoroughly review new methods that are used in place of animals. In an emailed statement, an FDA spokesperson wrote that the new law would not change the drug regulatory process. Appropriations bills passed at the end of 2022 also include his $5 million for agency programs aimed at evaluating alternative methods.
Also, different methods may be useful for testing different drugs or monitoring for specific side effects. It has to be shown to do,” says Locke. “It will be a scientific challenge, and it will take some time to do it.”
