Mimicking our insides

Homo chippiens, some have dubbed it. It's not a new species, but it certainly marks a new era in medical and biological research.

A growing number of scientists are working with ways to replicate how our organs function - and how they are affected by medicines or pollutants or other factors - by growing cells on computer chips.

One of the pioneers in what is called biomimicry, or organs on a chip, is Dan Dongeun Huh, an assistant professor of bioengineering at the University of Pennsylvania and principal investigator for its Biologically Inspired Engineering Systems Laboratory. He was part of a team at Harvard University that created the first organ on a chip, a lung.

Scientific benefits aside, because of the elegance of its design, that chip recently was acquired by the Museum of Modern Art in New York City and was given the Design of the Year award by the London Design Museum. Huh recently answered our questions about what putting organs - and even diseases - on chips could mean for the future of health care.

Why do we need organs on chips?

One of the traditional ways to study the human body is to take living cells from human organs and grow them in a culture medium in a hard plastic dish. We consider that a mimic of the human body, and we expect these cells to behave normally. But in reality, they don't. That's because these cells are used to a very complex and dynamic environment in our bodies. Traditional cell-culture models can't provide this kind of environment.

Another way is to use animals. But the genetic background and physiology of animals are very different from that of humans. So animal models, for the most part, fail to predict or simulate what happens in the human body.

Biologists and engineers have been working together to come up with a solution to this fundamental problem, which affects virtually all areas of biology and medicine.

What, exactly, is a lung on a chip?

What does it look like?

It's not the whole lung. But the structure is similar, and the environment is similar. We wanted to mimic the lung's air sacs. It's a microfabricated device that actually breathes.

It's about the size of a computer memory stick or a rubber eraser. It's made of optically clear silicone rubber - the same material as contact lenses. The device has microscopic channels separated by a thin porous membrane. On one side of the membrane, we culture lung cells. On the other side, we culture capillary cells. We flow air on the lung side and a bloodlike substance on the capillary side to mimic blood flow. There are two hollow chambers right next to the microchannels, and we apply vacuum suction to these to stretch the membrane and mimic breathing. This allows us to culture these human cells in a very bodylike environment, and replicate their original structure and function.

One of the most exciting aspects of this technology is that we can see things that are happening in our devices. We can directly observe and analyze complex biological responses. Also, we can precisely control the things we're putting into these models - for example, the types of cells, velocity of blood flow, concentration of chemicals.

After your published concept of the lung in 2010, you got a lot of response from drug companies. Why?

Right now, it costs more than $1 billion and takes more than 10 years to successfully develop one drug. The long delays and high costs are caused by the failure of drugs in human clinical trials.

The reason these drugs fail is because before they are tested on humans, they are tested on surrogate models like cell cultures or animals. But these models are failing to predict what's going to happen in the human body.

If drug companies are going to fail, they want to fail cheaply and early. We are aiming to help them by developing more predictive models of human organs for testing drugs before lengthy and expensive clinical trials.

Where is your research taking you now?

Understanding normal functions is important. But understanding disease is more important for a variety of things. We're focusing on building on this technology to create human disease models.

For example, we recently received a National Institutes of Health Director's New Innovator award to develop human asthma on a chip. During asthma, you get frequent constriction of the airways. When this happens, the cells experience abnormal mechanical forces - they get squeezed. But people don't really understand if and how these forces contribute to asthma development, progression and exacerbation. Our hypothesis is that the compression may play an important role. We're aiming to use this human asthma system to test this hypothesis.

Additionally, we have pulmonary fibrosis on a chip, and a smoking lung on a chip. We are "smoking" our devices to find out what cigarette smoke actually does to lung cells.

We are also branching out to other organs. We have a human blinking eye on a chip, mimicking the human cornea, to study dry-eye disease. We've received funding from the March of Dimes Foundation to develop a placenta on a chip and a cervix on a chip to study preterm birth. We have skin on a chip and a human gut on a chip.

Where could all this lead?

Right now, we're focusing on individual organ models. But the next step would be to link them to mimic physiology at the whole-body level - a human body on a chip.

Overall, for drug discovery, it has the potential to change the way drugs are developed and tested. For basic research, it will serve as an innovative and enabling tool. To be able to emulate the complex body, to be able to observe complex biological processes, and to be able to precisely control key players in these complex processes - to me, it's revolutionary.