In a move that could signal a shift in the way we test pharmaceuticals, researchers at Harvard University have developed a human lung on a chip. The tiny device contains actual human cells, mimicking the way the human lung works. Because it’s translucent, the chip constitutes a sort of window into the body.
The research was published in the journal Science.
“You’re seeing a breakdown of barriers,” said Dr. Donald Ingber, director of Harvard’s Wyss Institute for Biologically Inspired Engineering. ”We’re taking a technique used to make microchips for the computer industry, modifying it, mixing it with human cells. You’re seeing a man-machine interface, a bionic system that’s part-living, part-inorganic.”
I spoke recently with Ingber about the lung on a chip — and about what further advances to this technology could mean for the future of medicine.
How can a microchip mimic a breathing human lung?
It’s a very simple device that looks like a rectangular, clear, rubbery plastic eraser that has a thin channel down the center. We have two hollow channels that are placed against each other with a thin, flexible, porous membrane separating them. On one side of the membrane, we have human air sac cells from the lung. On the other side, we have human capillary blood vessel cells. We have air flowing through [and] on the blood side the fluid is flowing. Because the whole apparatus is flexible it stretches and relaxes, just like when you breathe.
Why was the microchip developed and what was the development process?
Everyone — even if you’re not in science — knows drugs are really expensive. It takes so long to go from discovery to the clinic. Lots of animals are used to get there. The animals are not only time consuming and expensive, but they often don’t predict what happens in humans. We set out to see whether we could develop a device that would mimic organ level functions with human cells that might be able to shortcut that process.
Dan Huh is a post-doc in my group. Dan, when he was a grad student, developed a device to model the airways and how you get fluid in your lungs when you get pneumonia. When you had fluid in this device, it would actually make a noise — the noise doctors are listening for when they put a stethoscope on your chest. If they hear it, there’s fluid on the lung [and there might be] an infection. That was amazing.
What really would be transformative is if we could not only model the structural part of the lung, but also the functional part. That’s what led to this device. Most of the functions of the lung occur in the air sac. That’s where gases are exchanged. If you have pneumonia [that is] where the immune cells migrate in. That’s where anesthetics are absorbed, where toxins from pollution are absorbed. We set out to model that structure.
There’s been a lot of work with living cells, but usually you have individual cells on a dish and they lose the specialized functions they normally have in the body. More recently, people have been doing tissue engineering where you have tissue-level functions, like the cells form a capillary tube. But an organ is composed of a combination of tissues that come together collectively to provide higher-level capabilities. We wanted to have the lining tissue of the air sac and the lining tissue of the blood vessel. They are juxtaposed very closely in your lung, separated by a membrane. That’s where all the exchange occurs.
The primary use for the microchip will be drug testing?
Right now we’re looking for drug screening, safety, toxicology. Drug discovery in terms of aerosol-based drugs is probably the biggest target.
We’re [also] working on guts on chips and kidneys and livers [on chips]. The idea is to link all these together and eventually have a human on a chip. [We hope to] be able to see an aerosol-based drug get absorbed, but if it gets modified by the liver and excreted by the kidney. This may go beyond just the lung and drug screening.
What’s the next step for the lung on a chip?
We’re talking to pharmaceutical companies about testing some of their compounds and seeing whether we could measure absorption, as well as toxicity. We’re working with companies to see whether we can pick out things in this chip that they’ve seen in animals or, better yet, in humans.
Image, top: Lung on a chip / Courtesy of the Wyss Institute for Biologically Inspired Engineering
Image, bottom: Dr. Donald Ingber