When 4,000 beagles destined for animal testing were recently rescued from a breeding facility in Virginia, it reminded us of the sheer size of animals used in the pharmaceutical industry and other research: an estimated 192 million animals are used in laboratories worldwide every year. .
Aside from the ethical challenges, the process doesn’t work very well. Of the drugs that pass animal tests, more than 90% later fail in human clinical trials. But better technology could replace the use of some animals — and make drug development cheaper and more effective. And eventually, as technology evolves, these and other alternatives may replace animal testing entirely.
Biotech company Emulate is one of the companies pioneering this technology. On one version of its tiny “organ on a chip,” about the size of a flash drive, human lung cells line two parallel channels carved into a flexible plastic. Another chip is implanted with brain cells; another has liver cells. The technology mimics what happens in the body, with nutrients, air and blood being pumped through the tiny ducts. “What we’re trying to do is recreate the simplest functional unit of any organ,” said Lorna Ewart, Emulate’s Chief Scientific Officer.
When the technology is used to test drugs, growing evidence suggests it may work better than testing on animals. And with some newer types of interventions, such as gene therapy or monoclonal antibodies, animal testing doesn’t work at all right now; an organ chip can help provide critical early feedback on 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 replace the number of animals used.
“We’ve used these 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,” said cell biologist and bioengineer Donald Ingber, founder and director. van Wyss of Harvard University. Institute, which led a team that pioneered the first successful organ chip in 2010. In 2014, Ingber released Emulate and is now a member of the 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 in simultaneous protection against COVID-19, the original SARS virus, multiple types of flu, MERS and the common cold. “We did that very quickly and found that it works 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. “One was looking at cells in a dish, a very artificial environment,” says Ewart. “And the other is, of course, an animal model. And I think there’s a lot of data showing that these two models don’t really help scientists in the field of drug development choose the right candidate, both from a safety and efficacy standpoint.”
For example, some drugs used to treat liver disease bind to proteins in the human liver in a way not found in animals; researchers saw no toxic effects until human trials began. Other drugs that have shown promise for treating Alzheimer’s disease in animals don’t work when tested on humans. Some cancer drugs that eliminate tumors in mice don’t perform as well in humans. And the list goes on. (One Twitter account is devoted solely to pointing out hyperbolic press releases about new drugs that don’t mention that the results have only been shown in mice and therefore probably won’t work in humans.)
In a study currently under peer review, Emulate scientists, 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 hit the market, 22 of which were later discovered to be harmful to the liver.
“Twenty-two of those drugs have undergone animal testing and were in fact identified as safe enough to be included in clinical trials, but were later either withdrawn from the market or had to be labeled on a black box,” said Emulate CEO Jim Corbett. (Before being removed, the drugs killed 208 patients and required 10 others to receive a liver transplant.) The liver chip technology was seven to eight times more accurate at identifying toxicity than the animal tests had been.
The technology of organ chips is still in its infancy. Emulate first focused on using the tools to test drug safety. The next step is to test its efficacy more so that researchers can better understand how drugs might work before clinical trials begin. For example, the technology can be used with samples of cells from patients with rare diseases before it is actually used directly on those patients.
To help increase the use of the technology, regulatory change is an important step: A bill recently passed with bipartisan support by the House, the FDA Modernization Act, would update the requirements for drug companies to enter a drug into clinical trials. want to move. The guidelines have not changed since 1938. “For the first time, this would mean you can submit alternatives to animal data,” says Corbett.
Pharmaceutical companies may also begin to use the technology more in internal drug development, as it has the potential to save several billion dollars spent on drugs that ultimately don’t work. The recent study of drug toxicity on the liver calculated that if drug companies only used Emulate’s liver chip, they could save $3 billion a year.
“Replacing animal testing for these pharmaceutical companies is very difficult because you have people who don’t want to take a risk and change the way they do things,” says Ingber. “But maybe its economics will catch the attention of C-suite folks.”