Artificial body: how to grow your own personal lab rat, on a chip

Brain, heart, liver, intestine and kidney: human organs can be grown on a chip. This technique helps to reduce animal testing and opens the door to medicines for diseases that are currently incurable. But who’s gonna feed the chips tonight?

It looks like a chip like any other: a flat square with some soldered connections and electronics. But in the middle is a tiny plastic swimming pool in which a miracle takes place. If you fill this small container with a physiological saline solution, a piece of the human brain can grow in it. Or a piece of lung, heart, intestine, liver or kidney, grown from stem cells. It's organ meat, on a bed of silicon.

These mini-organs are a daily occurrence for Chiara Diacci of the Flemish research institute imec and a specialist in bioelectronics. On a table in the Antwerp conference centre, Diacci shows the chips she and her colleagues are working on: semiconductors that measure how human tissues respond to medicines. It is a digital revolution in the making, in which the artificial body plays the leading role rather than artificial intelligence. "Soon everyone will have their own Mini-Me," says Diacci. She's referring to comedy movie Austin Powers ("yeah baby!"), in which villain Dr. Evil was joined by a small clone of himself.

At imec's annual conference ITF, which was held in Antwerp recently, everything revolved around chips. And especially the chips that offer extra computing power, for the holy grail of Silicon Valley: artificial intelligence that can compete with the human brain. Hundreds of billions of dollars are being pumped into AI start-ups and omniscient assistants, which? are doubtful they will ever make money.

'OoC' (Organ on Chip) is a less sexy abbreviation than 'AI', but it solves a much more tangible problem. Human and animal lives are at stake. With the test data from mini-organs, pharmaceutical companies can accelerate the development of new drugs. That process still takes years, is outrageously expensive and extremely inefficient.

Unhealthy industry

Just how economically unhealthy the pharmaceutical industry is is shown by the figures from research firm Deloitte: in 2022, the twenty largest companies invested $139 billion in drug development, and that investment had a return of 1.2 percent – the lowest level since 2010.

Stricter regulation – intended to prevent dangerous mistakes with approved drugs – means fewer drugs from the lab end up on the bedside table. The rules are too strict for current testing methods, and as a result, many potential drugs do not make it to the finish line.

Organs on chips help to increase the effectiveness of preclinical studies and reduce the use of laboratory animals. According to Animal Rights, 115 million laboratory animals are 'used' worldwide, in the Netherlands this is half a million animal experiments per year.

For many medicines, animals do not give a good indication of the effect on humans. Biomedical scientist Dries Braeken of imec explains: "Drugs are becoming more complex, such as immune cells that attack tumors. It's difficult to test that on a mouse, but you can test it with an organ chip that mimics the interaction with the immune system."

Barrier in the brain

A container with a few tens of thousands of brain cells does not produce a working brain – a human brain has as many as 86 billion cells. But you can mimic certain functionality, such as the blood-brain barrier.

Unlike alcohol or caffeine, medications struggle with that natural boundary between brain and bloodstream. This hinders the fight against brain diseases such as Alzheimer's and Parkinson's. If you can safely break through the blood-brain barrier – smuggling medicines in via a kind of 'Trojan Horse' – it opens up new possibilities.

Braeken cites ALS, the debilitating nerve-muscle disease, as an example. "There is an American therapy that works in a fraction of ALS patients, in which the disease process seems to be partially reversed. They have to be injected every month, into the brain, through the skull. For large-scale applications, drug delivery needs to be? improved."

The blood-brain barrier is one of the many holy grails of OoC development. In addition to the large organs, specific bodily functions are also recreated, such as a retina-on-a-chip to test drugs against eye diseases, or a hearing organ-on-a chip to combat deafness.

The U.S. ?FDA has been encouraging the use of organ chips since last year. This is an important incentive for commercial applications. Dutch companies such as Mimetas from Leiden are entering this market. The National Growth Fund – when it had not yet been killed by the upcoming coalition – also invested millions in the development of 'miniature diagnostics'.

Dutch scientists are quite good at organ-on-chips, says Andries van der Meer. He is a professor at the University of Twente, where he leads the OoC expertise centre, and is 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. The conventional methods with cultured cells, tissues and laboratory animals will not be completely 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, and the biggest costs are in the clinical trials, at the end of the development process. More than 80 percent of the candidate drugs are still eliminated at that stage. If you improve the conversion rate a fraction, it saves a lot of money.

Body-on-a-chip

Standardisation is still needed, for sensor data and for the sizes of the chips: these must match the methods currently used by pharmaceutical laboratories. A standard for linking the chips helps to build 'multi-organ' chips, for example a system with intestines and kidneys. As with computers, this should be a matter of plug and play.

Other options: a 'disease-on-a-chip', a 'patient-on-a-chip', to tailor medicines. This personal 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 keeps you up to date constantly, because the chips only 'live' for a few months. That is the pharmaceutical future: everyone has their own body-on-a-chip, a Mini-Me as a personal laboratory animal.

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

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This article by Marc Hijink was published in Dutch, in national newspaper NRC on May 25, 2024 and translated by AI. Read more episodes of ‘Achter de schermen / Behind the scenes’ at NRC.