When 4,000 beagles earmarked for animal testing were recently rescued from a breeding facility in Virginia, it reminded us of the scale of animals used in the pharmaceutical industry and other research: by one estimate, 192 million animals are used in laboratories each year worldwide. .
Beyond the ethical challenges, the process is not working very well. Of the drugs that pass animal testing, more than 90% later fail in human clinical trials. But better technology could begin to replace the use of some animals and make drug development cheaper and more efficient. And eventually, as technology evolves, perhaps this and other alternatives could completely replace animal testing.
Biotechnology company Emulate is one of the pioneering companies in this technology. On a version of his tiny “organ-on-a-chip,” roughly the size of a USB key, human lung cells line two parallel channels carved into flexible plastic. Another chip is implanted with brain cells; yet another has liver cells. The technology mimics what happens inside the body, with nutrients, air and blood pumped through the tiny channels. “What we’re trying to do is recreate the simplest functional unit of each organ,” says Lorna Ewart, scientific director of Emulate.
When the technology is used to test drugs, growing evidence suggests it may work better than animal testing. And in the case of some newer types of interventions, like gene therapy or monoclonal antibodies, animal testing currently doesn’t work at all; an organ chip could help provide critical early feedback on a drug‘s safety or effectiveness. In its current form and under current regulations, organ chip technology cannot completely replace animal testing. But it has the potential to significantly replace the number of animals used.
“We use them either to reuse existing drugs that are in clinical trials or to develop new drugs using these chips, and we can do them faster and cheaper,” says the cell biologist and bioengineer Donald Ingber, founding director of Harvard University’s Wyss. Institute, which led a team that launched the first successful organ chip in 2010. In 2014, Ingber created Emulate and now sits on its board of directors.
At Harvard, Ingber’s team used the technology to identify an existing drug to treat COVID-19, which is currently undergoing clinical trials in Africa. He has also developed a new treatment that shows promise for simultaneously protecting against COVID-19, the original SARS virus, several types of influenza, MERS and the common cold. “We did this very quickly and determined that it worked in these human chips and other models,” he says. “I think he has huge potential.”
Before organic chip technology became available, pharmaceutical companies had two main options for testing. “One of them was looking at cells in a box, a very artificial environment,” says Ewart. “And the other, of course, is an animal model. And I think there’s a lot of data that shows that actually those two models don’t really help drug development scientists choose the right one. candidate, whether from the point of view of safety or effectiveness.
Some drugs used to treat liver disease, for example, bind to human liver proteins in a way that does not occur in animals. researchers did not see any toxic effects before human trials began. Other drugs that have shown promise for treating Alzheimer’s disease in animals don’t work when tested in humans. Some cancer drugs that kill tumors in mice don’t work as well in humans. And the list continues. (One Twitter account is dedicated only to pointing out hyperbolic press releases about new drugs that don’t mention that the results have only been shown in mice and are therefore unlikely to work in humans. .)
In a study currently under peer review, scientists from Emulate, along with pharmaceutical companies Johnson & Johnson and Abbvie, found that liver chips worked much better than animals at predicting whether a particular drug would be toxic. . The study looked at 27 different compounds used in drugs that came to market, 22 of which were later found to be harmful to the liver.
“Twenty-two of these drugs were tested on animals and were identified as safe enough to move into clinical trials, but later either were taken off the market or required black-box labeling,” says Jim Corbett, CEO of Emulate. (Before being withdrawn, the drugs killed 208 patients and required 10 more liver transplants.) Liver chip technology was seven to eight times more accurate at identifying toxicity than animal testing.
Organ chip technology is still in its infancy. Emulate initially focused on using the tools to test drug safety. The next step is to do more efficacy testing, so researchers can better understand how the drugs may work before clinical trials begin. The technology could be used with cell samples from patients with rare diseases, for example, before it is actually used directly in those patients.
To help increase technology use, regulatory change is a key step: A bill recently passed by the House with bipartisan support, the FDA Modernization Act, would update requirements for pharmaceutical companies wishing to move a drug into clinical trials. The guidelines haven’t changed since 1938. “For the first time, it would mean you could submit alternatives to animal data,” says Corbett.
Pharmaceutical companies could also start using the technology more in in-house drug development, as it has the potential to save some of the billions of dollars spent on drugs that ultimately don’t work. The recent Liver Drug Toxicity Study calculated that if pharmaceutical companies only used Emulate’s liver chip, they could save $3 billion a year.
“Replacing animal testing for these pharmaceutical companies is really difficult, because there are people who don’t want to take the risk and change the way they do things,” Ingber says. “But maybe the economy of this one will catch the attention of the C-suite folks.”