How human ‘organs on a chip’ can help replace animal testing

When 4,000 Beagles Animals destined for testing were recently rescued from a breeding facility in Virginia, reminiscent of the sheer scale of animals used in the pharmaceutical industry and other research: by one estimate, 192 million Animals are used in laboratories around the world every year.

Beyond the ethical challenges, the process doesn’t work very well. More than 90% of drugs that pass animal testing subsequently fail in human clinical trials. But better technology could replace the use of some animals – and could make drug development cheaper and more effective. And eventually, as technology develops, perhaps this and other options could replace animal testing entirely.

emulate organ-chip [Image: Emulate]

biotech firm simulation is one of the companies pioneering this technology. On a version of their tiny “organ on a chip,” roughly the size of a flash drive, human lung cells carve two parallel channels into a flexible plastic. Another chip is implanted with brain cells; Yet another contains liver cells. The technology mimics what happens inside the body with nutrients, air and blood pumped through tiny channels. “What we’re trying to do is to recreate the simplest functional unit of every organ,” says Lorna Ewart, Amulet’s chief scientific officer.

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[Photo: Emulate]

When the technology is used to test drugs, mounting evidence suggests that it may work better than testing on animals. And in the case of some newer types of interventions, such as gene therapy or monoclonal antibodies, animal testing currently doesn’t work at all; An organ chip can help provide important initial feedback about whether a drug is safe or effective. In its current form – and under current regulations – organ chip technology cannot completely replace animal testing. But it has the potential to significantly change the number of animals used.

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[Photo: Emulate]

“We are using these to either repurpose existing drugs that are in clinical trials or develop new drugs using these chips,” says Donald Ingber, founding director, cell biologist and bioengineer at Harvard University. and we can do them faster and cheaper.” Vice Institutewho led the team that pioneered the first successful organ chip in 2010. In 2014, Ingber spun out Emulate, and now serves on its board.

At Harvard, Ingber’s team has used the technology to identify an existing drug to treat COVID-19, which is now in clinical trials in Africa. It 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 it very quickly, and determined it worked in these human chips and in other models,” he says. “I think it has huge potential.”

Before organ chip technology was available, pharmaceutical companies had two main options for testing. “Was looking at the cells in a dish, a very artificial environment,” Ewart says. “And the other, of course, is an animal model. And I think there’s a lot of data that shows that, in fact, those two models don’t really help drug development scientists pick the right candidates, either safety.” Or from the point of view of efficacy.”

Some drugs used to treat liver disease, for example, bind to proteins in the human liver in a way that does not occur in animals; Researchers did not notice toxic effects until human trials began. Other drugs that have shown promise for treating Alzheimer’s disease in animals have not worked when tested in humans. Some cancer drugs that eliminate tumors in mice do not perform well in humans. And the list goes on. (A Twitter account dedicated solely to pointing out exaggerated press releases about new drugs that It fails to mention that the results have only been demonstrated in rats—and therefore may not be likely to work in humans.,

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Simulate organ-chip with SEM (scanning electron microscopy) image of colon gut-chip epithelium [Image: Emulate]

one in study Currently under peer review, scientists at Amulet, along with pharma companies Johnson & Johnson and AbbVie, found that liver chips do a better job than animals at predicting whether a particular drug will be toxic. The study looked at 27 different compounds used in the drugs that made it to market, 22 of which were later discovered to cause liver damage.

“Twenty of those drugs went through animal testing, and were originally identified as safe enough to go into clinical trials, yet were later pulled from the market, either or was necessary black box labeling,” says Amulet CEO Jim Corbett. (Before they were pulled, the drugs killed 208 patients and 10 others required liver transplants.) The liver chip technique was seven to eight times more accurate than animal testing at identifying toxicity.

Organ chip technology is still in its early stages. Emulate has first focused on the use of devices to test drug safety. The next step is to do more testing of efficacy, so researchers can better understand how the drugs might work before clinical trials begin. The technique could be used with samples of cells from patients with rare diseases, for example, before it is actually used directly in those patients.

To help increase the use of the technology, the change in regulation is an important step: a bill recently passed in the House with bipartisan support, the FDA Modernization Act, would update requirements for drug companies to buy a drug. to move to clinical trials. The guidelines have not changed since 1938. “For the first time, it will say that you can submit alternatives to animal data,” Corbett says.

Pharma companies may also begin to use the technology more in internal drug development, as it has the potential to save billions of dollars spent on drugs that ultimately don’t work. A recent study of drug toxicity on the liver calculated that if drug companies used Amulet’s liver chip alone, they could save $3 billion annually.

“It’s really hard for these drug companies to replace animal testing, because you have people who don’t want to take the risk and change the way they work,” Ingber says. “But maybe its economics will catch the attention of people in the C-suite.”

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