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This Boston startup is chipping away at animal testing

Emulate Bio, a spinout from the Wyss Institute at Harvard, hopes its “organ-on-a-chip” technology will reduce or replace some forms of animal testing

Boston startup Emulate Bio is developing “organ-on-a-chip” devices that allow scientists and drug developers to run tests on artificial human "organs" that it hopes will one day reduce or eliminate animal testing.Jessica Rinaldi/Globe Staff

It’s no secret that most drugs tested on animals prove to be unsafe or ineffective in people. As many as 9 out of 10 experimental medicines fail in clinical trials, a statistic that has many animal welfare activists and scientists alike wondering if there’s a better way.

“The failure rates, compared to any other industry, are just crazy,” said Jim Corbett, chief executive of the Boston startup Emulate Bio, which might have a solution to the problem.

Over the past decade, Emulate has raised more than $200 million to develop its so-called organ-on-a-chip technology, based on work from the Wyss Institute of Harvard University. The organ chips are clear, flexible, flash drive-sized devices with tiny channels that house living human tissue designed to imitate cells in an organ such as the brain, kidney, or liver.


The idea isn’t new. Scientists have been tinkering on miniature organ systems that mimic the human body in a lab dish for several decades. And while many of these organ chips were impressive technical projects in their own right, they were either too unwieldy or unreliable to usurp animals.

“It looks simple, and in a sense it is,” said Shuichi Takayama, a biomedical engineering professor at Georgia Tech. “But making it reproducible and user-friendly enough for biologists has taken a lot of effort.”

The tide is slowing turning, thanks to a flurry of advances and investments in the technology since 2010. Dozens of biotech startups are entering the space, and a recently passed law could help organ chips become mainstream by encouraging drug makers and regulators to consider alternatives to animals.

“Drug developers all know that animals are a problem, and they would love to have a replacement,” said Donald Ingber, director of the Wyss Institute and an organ chip researcher who founded Emulate. “Now it’s up to them. And once one company is able to successfully get a drug to clinical trials faster, with less money, and makes a lot of money, everybody’s going to start to do it.”


Since 1938, the Food and Drug Administration has required companies to test experimental medicines in animals — often a combination of rodents, dogs, or monkeys — to make sure they seem safe enough to test in humans.

Athanasia “Nasia” Apostolou, a senior scientist at Emulate, brings her dog to work. The Boston startup is developing “organ-on-a-chip” devices that allow scientists and drug developers to run tests on artificial human "organs" that it hopes will one day reduce or eliminate animal testing. Jessica Rinaldi/Globe Staff

But the door opened to change in late December when President Biden signed a bill that empowers the FDA to greenlight clinical trials with evidence from organ chip studies or other alternatives to animals. The agency still has power to require animal tests, if it deems them necessary, so some experts question how big of an impact the new law will have.

“It’s a nice message, but doesn’t really change things a whole lot,” said Tim Petrie, who leads the organ chip business at Draper Laboratory in Cambridge. With organ chips, scientists and drug developers still view them as “nice-to-have, but not need-to-have, which is a roadblock to adoption,” he said.

But Corbett hopes the law will help “break down a perceived nervousness” about submitting data from organ chips. “Our endgame clearly is to eliminate animal testing, but there needs to be a body of evidence created first,” he said. “What you’ll probably see is a slow reduction in the amount of animals being used.”

The modern incarnation of organ chips arrived in 2010, when Ingber’s lab developed a lung-on-a-chip with two layers of lung cells, one side exposed to air and the other exposed to fluids that could deliver nutrients or drugs. When they submitted their research for publication, the reviewers “totally turned it down,” Ingber said. “They wanted animal models.”


Brushing the irony aside, Ingber’s team went back and conducted experiments on mice to show that their lung-on-a-chip bore resemblance to the real organ. “We really were able to predict things that nobody knew about happening in lung,” including immune reactions that they discovered on the organ chips and replicated in mice.

When the results were published in the prestigious journal Science in 2010, it was a watershed moment for organ-on-a-chip technologies. “That made a big splash,” said Michael Shuler, chief executive of Hesperos, a biotech company in Florida developing similar “body-on-a-chip” technology.

Suddenly scientists at the FDA and the National Institutes of Health, the biggest funder of biomedical research, began talking about how organ chips might be useful tools, and not just cool science projects. Funding began pouring into Ingber’s lab to help develop new organ chips, including a $37 million grant from DARPA, a moonshot research division of the Department of Defense.

The Wyss hired roughly 45 people, many of whom left industry jobs, to develop organ chips for nearly every part of the body. The group saw themselves as a startup, and before long, they were. Ingber founded Emulate Bio in 2013, and the company launched with following year with $12 million and about 20 former Wyss scientists to further develop and commercialize the organ chips.


Scientist Marianne Kanellias, left, brings a row of “organ-chips” to research associate Adriana Cespedes as they demonstrate how the “organ-on-a-chip” devices work. Jessica Rinaldi/Globe Staff

“We’re never going to get these organ chips to replace animal testing if everybody makes their own chip,” Ingber said. “You need industry to come in and mass produce the chips with reproducibility.”

Today, Emulate sells lung, liver, brain, kidney, and intestine organ chips, as well as blank chips that researchers can add other cells to. It also runs experiments for companies in its labs in Boston’s Seaport district. The single-use chips go for about $600 each and a pair of machines required to use them cost over $110,000.

Because Emulate is still a private company, the scope of its business is unclear. Corbett wouldn’t share his firm’s sales or number of clients, only stating that it counts the majority of top pharma companies as customers, including AstraZeneca, Johnson & Johnson, and Roche. So far, most big drug companies are only “dabbling” in the organ chip technology, he conceded.

The company hopes that its liver chip could help change that. Roughly a third of drugs fail clinical studies due to safety concerns, and the most common issue is liver toxicity. Emulate gathered several drugs that previously passed muster in animal tests but later proved unsafe when tested in humans. In a blinded study, the liver chips correctly predicted 87 percent of the drugs that were toxic.

“I never in my life thought that we would be able to detect that many drugs that had gone through animal testing, at such a high degree of accuracy,” Corbett said. The results were published in the journal Communications Medicine in December.


Most organ chip experts suspect that the technology will make inroads by proving that it is superior to animals in narrow applications. For instance, the NIH is looking to fund work on organ chips that mimic the junction between nerves and muscles. Danilo Tagle, who leads the “tissues chips” program at the NIH, thinks such chips could replace the roughly 6 million mice killed each year to test the potency and safety of botulism toxin, used in Botox.

Many experts say that testing drug effectiveness, rather than safety, is more difficult because it requires the chip to accurately simulate the complexities of a disease. But Corbett said this represents “an even greater opportunity” for reducing animal testing, and growing his business, in the long run.

Ingber believes organ chips will help scientists find answers to questions they can’t resolve with animals, including in personalized medicine, where organ chips can be made from a patient’s own stem cells. In his eyes, organ chips are about improving medicine, not just replacing animal testing.

“We know animal models are wrong more than 50 percent of the time. Who would ever make decisions based on results like that?” Ingber said. “This is about transforming drug development.”

Athanasia Apostolou, a senior scientist at Emulate, pulls a row of “organ-chips” out of a culture module. Jessica Rinaldi/Globe Staff

Ryan Cross can be reached at Follow him on Twitter @RLCscienceboss.