Artificial Body: With Organs-on-Chips, You Can Grow Your Own Test Animal

Brains, heart, liver, intestine, and kidney: human organs can grow on a chip. This technique helps reduce the use of test animals and opens the door to treatments for currently incurable diseases. The magic of the artificial body.

It looks like any other chip: a flat square with some soldered connections and electronics. But in the middle is a small plastic pool where a tiny miracle occurs. Fill this small dish with a physiological saline solution, and a piece of human brain can grow in it. Or a piece of lung, heart, intestine, liver, or kidney, cultivated from stem cells. It is organ tissue, on a bed of silicon.

These mini-organs are daily fare for Chiara Diacci of the Flemish research institute Imec and a specialist in bioelectronics. At a table in the Antwerp conference center, Diacci shows the chips she and her colleagues are working on: semiconductors that measure how human tissues respond to drugs. It is a digital revolution in the making, where not artificial intelligence but the artificial body takes center stage. “Soon everyone will have their own Mini-Me,” says Diacci. She refers to the comedy film Austin Powers (‘Yeah baby!’), where villain Dr. Evil is accompanied by a small clone of himself.

At imec’s annual conference, held last week in Antwerp, everything revolved around chips. Especially chips that offer extra computing power, for Silicon Valley’s holy grail: artificial intelligence that can compete with the human brain. Hundreds of billions of dollars are being pumped into AI startups and omniscient assistants, whose profitability is questionable. ‘OoC’ (Organ on Chip) is a less sexy acronym than ‘AI’, but it solves a much more tangible problem. It concerns human and animal lives. With the test data from mini-organs, pharmaceutical companies can accelerate the development of new drugs. This process currently takes years, is outrageously expensive, and extremely inefficient.

Unhealthy Industry

How economically unhealthy the pharmaceutical industry is, is evident from figures from research firm Deloitte: in 2022, the twenty largest companies invested $139 billion in drug development, with a return of 1.2 percent – the lowest level since 2010.

Due to tightened regulations – intended to prevent dangerous mistakes with approved drugs – fewer drugs from the lab end up on the bedside table. The rules are too strict for current test methods, causing many potential drugs not to make it to the finish line.

Organ-on-chips help increase the effectiveness of preclinical studies and reduce the use of test animals. According to Animal Rights, 115 million test animals are ‘used’ worldwide, with half a million animal experiments conducted annually in the Netherlands.

For many drugs, animals do not provide a good indication of the effect on humans. Biomedical scientist Dries Braeken of imec explains: “Drugs are becoming more complex, such as immune cells attacking tumors. You can’t easily test that on a mouse, but you can with an organ chip that mimics the interaction with the immune system.”

Barrier in the Brain

A dish with tens of thousands of brain cells does not produce a functioning brain – a human brain contains 86 billion cells. But you can mimic certain functionalities, such as the blood-brain barrier.

Unlike alcohol or caffeine, drugs have difficulty crossing this natural boundary between the brain and the bloodstream. This hinders the treatment of brain diseases like Alzheimer’s and Parkinson’s. If you can safely breach the blood-brain barrier – smuggling drugs inside via a sort of ‘Trojan horse’ – new possibilities open up.

Braeken mentions ALS, the debilitating nerve-muscle disease, as an example. “There is an American therapy that works for a fraction of ALS patients, seemingly reversing part of the disease process. However, they need monthly injections into the brain, through the skull. For large-scale applications, drug delivery needs to be better.”

The blood-brain barrier is one of many holy grails of OoC development. In addition to major organs, specific body functions are also being replicated, such as a retina-on-a-chip to test drugs against eye diseases or an ear organ-on-a-chip to combat deafness. The American FDA has been promoting the use of organ chips since last year. This is a significant boost for commercial applications. Dutch companies like Mimetas from Leiden are diving into that market. The National Growth Fund also invested millions in the development of ‘miniature diagnostics‘ – before it was potentially dismantled by the upcoming coalition.

Dutch scientists are proficient in organ-on-chips, says Andries van der Meer. He is a professor at the University of Twente, leads the OoC expertise center there, and is the chairman of the European Organ-on-Chip Society. But the organ chip is not a panacea, he emphasizes. “The technology will have to prove itself step by step. Conventional methods with cultured cells, tissues, and test animals will not be fully replaced.”

Van der Meer has no doubts about the commercial potential. It costs an average of $2.3 billion to bring a drug to market, with the biggest costs in clinical trials at the end of the development process. More than 80 percent of candidate drugs still fail at that stage. If you slightly improve the success rate, it saves a lot of money.

Body-on-a-Chip

There is still a need for standardization, for sensor data, and the sizes of the chips: they must fit the methods currently used by pharmaceutical laboratories. A standard for linking the chips helps build ‘multi-organ’ chips, such as a system with intestines and kidneys. Like computers, it should be a matter of plug and play.

Other options: a ‘disease-on-a-chip’, a ‘patient-on-a-chip’, to create personalized drugs. This personalized approach is costly and takes months to reprogram stem cells into mini-organs. According to Van der Meer, you should have a live organ chip that you constantly monitor, as the chips only ‘live’ for a few months. That is the pharmaceutical future: everyone with their own body-on-a-chip, a Mini-Me as a personal test animal.

It is a fantastic field, Van der Meer believes, at the intersection of technology and biology. With one small drawback: some types of organs need nutrients every other day, such as glucose. “That means you also have to go to the lab on weekends, to feed the chips.

Animation by Roel Venderbosch

This article & photo is taken from the Dutch NRC website.