Testing Drugs on Chips, Not Chimps: Replacing Livers with Circuits

The cost of developing new drugs is about more than money. For every new pharmaceutical that labs develop around the world, there are significant regulatory hurdles they must overcome before the drug is considered safe for trials with humans — and that includes evidence that it works in other animals first. Such species include rats, mice, fish, and, most controversially, primates.

Genetically similar to humans, creatures like chimpanzees or rhesus monkeys give researchers the confidence that a drug safe for them will be likewise safe for the first humans to take it in trial — and (with some rare, nasty exceptions) it’s a model that’s worked successfully for decades. Animal testing has led to insights that have given us myriad examples of vital drugs, from the polio vaccine to asthma medication. As attitudes shift, however, and research moves away from using chimpanzees and other great apes, there remains a fundamental problem: how to test the way a new drug will work inside a human, without actually testing it inside a human.

Part of the solution could be a smartphone-sized piece of plastic, like the one being constructed in a lab in Welwyn Garden City, about half an hour north of London by train. This plastic holds anywhere between a dozen and 36 tiny synthetic human livers, and hundreds of thousands of human cells, that react just like the full, real organ when exposed to drugs during tests.

This liver-on-a-chip works by condensing and simplifying the essential parts of what a liver is — each one has several thousand liver cells hanging off of a plastic scaffold that mimics the strength and flexibility of a real liver, while tiny micropumps keep a constant flow of artificial blood pumping through.

The small number of cells necessary to make each liver-on-a-chip work means that cells can be sourced from donor offcuts that hospitals or other researchers normally have no use for (due either to their size or how damaged they are). CN Bio Innovations, the startup behind the liver chip, claims that using its product will be “significantly” cheaper than the equivalent animal testing for many drugs. The complete lifecycle for the cells, and whatever infects them, can be observed in one tiny space.

CN Bio calls its system, appropriately enough, LiverChip; and its current focus is on one specific disease as a proof-of-concept: Hepatitis B, a viral liver disease enormously prevalent around the world. The WHO estimates that there are roughly 240 million people living with chronic Hep B infections, while more than three-quarters of a million people, overwhelmingly in Asia and sub-Saharan Africa, die from it each year — despite a readily available vaccine and several treatments to manage its symptoms. However, there is no cure yet, making it an attractive candidate for research.

The tech behind LiverChip was originally developed at MIT, funded by the U.S. government’s cutting-edge scientific research wing DARPA as part of a wider program to develop organs-on-a-chip for the entire human body. CN Bio is currently working out how to turn it into something commercially viable, and has deals with a few (mostly still unnamed) pharmaceutical companies, like the Australian firm Benitec. The company also has research collaborations with institutions like Imperial College London. It can cost pharmaceutical companies upwards of a billion dollars from start to finish to bring a drug to market, so there’s understandable interest in anything that could reduce some of those expenditures.

Eventually, we might reach a time when we have entire human bodies represented on chips, but for now the liver is complex enough on its own. According to David Hughes, CN Bio’s CTO, the engineering challenges for one organ are “extraordinary.”

But will this ever be a replacement for animal testing? “There’s a tension between the need for animal testing, and the desire not to have to use them,” Hughes explained at the opening of the company’s new research lab. For the near- and medium-future, it’s only going to be “supplemental” to animal testing, not a replacement, he said. It’s up to legislators and industry experts to continually assess the viability of organ-on-a-chip technology as it rolls out and improves, and decide at which point our need to test possibly dangerous drugs on animals is no longer necessary.