Developing and testing a new drug is a long, expensive process.
After extensive research to come up with a promising compound or molecule, scientists have to test it in animals to prove it’s safe for people to try it.
Next come a few rounds of clinical trials in people to see whether what seemed like a good thing in the lab is actually safe and effective in people, and at what dosage it works best.
Scientists have been working on a way to streamline this process by simulating organs on small chips, with living human cells arranged to mimic the structure of their full-size inspirations. These organ-on-a-chip systems may one day replace animal models and leave less testing to be done on human patients.
As Sara Reardon reports in Nature News, this futuristic vision is beginning to become reality.
An organ you can hold in your hand
Organs-on-chips are built on clear pieces of silicone made like computer microchips are: by pouring liquid silicone into a specially-etched mould and letting it harden.
The mould makes channels in the silicone that scientists can grow human cells in. The cells grow on the bottom of the channel, and fluid flows over them to deliver nutrients, the drug being tested, or anything else the scientists want the cells to encounter.
That’s the most basic organ-on-a-chip setup — only one type of cell in one channel with fluid flowing over it. To model the way different organs work, scientists add features to this basic idea.
For example, the lung-on-a-chip developed by scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University has a couple more levels of complexity to simulate a breathing lung.
A thin membrane separates the basic channel into two compartments. Scientists put different types of lung cells in each compartment: the type that interact with air on top of the membrane and the type that interact with blood on the bottom.
To make the lung-on-a-chip “breathe,” the scientists have air blown into the top compartment, while fluid mimicking the blood flows through the bottom. They can see what molecules in air make it through the lung and into the blood (in a human body, this is how we get oxygen from the air for blood to take to all of our cells that need it).
In another experiment, they were able to demonstrate that a cancer drug causes fluid to leak from the blood side of the membrane to the air side — just like it does in human lungs, causing the lungs to fill up with fluid and making it harder for the patient to breathe.
From labs to industry
Partnerships between biotechnology and pharmaceutical companies are bringing together organ-on-a-chip systems with drugs that need testing.
Reardon writes that Mimetas, a biotechnology company from the Netherlands, has developed a kidney-on-a-chip that three large pharmaceutical companies are already testing drugs on.
In addition, Johnson & Johnson has announced plans to test drugs on chip systems from Emulate, a Massachusetts-based biotech company with ties to Harvard’s Wyss Institute. According to a press release, the companies have already begun testing drugs on a chip system that models the way blood clots in the body, and are also planning to use a liver-on-a-chip to see if drugs damage the liver.
Blood clots and liver damage are common potential side effects of drugs, so testing in chip systems could screen out drugs with these effects before trying them on people in clinical trials.
What’s so great about organs-on-chips?
These tests are important tryouts for organ-on-a-chip systems, which are thought to have the potential to improve the way drugs are currently tested in a few major ways:
- They could reduce the amount of testing that needs to be done on people. Currently, companies have to test a new drug’s safety, as well as a wide range of doses on patients during clinical trials. Testing safety and fine-tuning doses in chip systems instead of patients could allow companies to skip these steps in people, Reardon writes. Scientists testing drugs in a chip model for lung cancer found the most effective dosages it predicted were closer to those determined during clinical trials in humans than those suggested by earlier, conventional tests on cells in petri dishes.
- Chip systems reproduce 3-dimensional structures like those in the body better than a petri dish full of cells laying flat next to each other, which is important in studying complex organs like the brain, or organs such as the placenta that are hard to study in action.
- Testing new drugs on chip systems could yield more accurate results than animal models. The results of animal studies can be misleading — a drug may have bad side effects in the animal that it won’t in humans (preventing a good drug from getting to market), or the animal might not have a problem with the drug that humans will experience (leading to expensive failed clinical trials, or worse, drugs that cause harmful side effects becoming available to the public).
As with any developing technology, significant hurdles remain for organ-on-a-chip systems.
To start, chip organs are still way less complex than real human organs, and they can’t yet copy the way organs are affected by other organs not close to them in the body. For example, they might not be able to model all the complicated ways hormones such as insulin, which is released from the pancreas, change the behaviour of faraway cells like those in muscles.
Plus, scientists are still testing whether existing drugs even act the way we expect them to on chip systems.
Despite these limitations, pharmaceutical companies are getting involved in development, as well as the US National Center on Advancing Translational Sciences (NCATS), a division of the National Institutes of Health, which is funding work on an 11-organ “human-body-on-a-chip” system.
If organ chip systems prove their merit for testing drugs, they could make getting new treatments to patients who need them faster, more accurate, and more cost-effective. That would be a welcome change to the field of medicine, and it’s just beginning to seem plausible.
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