The end of animal testing? Human-organs-on-chips

They may look like humble little blocks, but these miracle devices could end animal testing, revolutionize the development of new drugs and lead us into a world of entirely personalized medicine.

Tiny tubes emerge from a small transparent block, pumping imperceptible amounts of fluid and air to and fro. It looks like a Fox’s Glacier Mint has been plugged into a life support machine, but this humble chunk of see-through silicone is a model organ that could revolutionise the pharmaceutical industry, reducing the need for animal testing and speeding up the development of new drugs.

Meet the Lung-on-a-chip, a simulation of the biological processes inside the human lung, developed by the Wyss Institute for Biologically Inspired Engineering at Harvard University – and now crowned Design of the Year by London’s Design Museum.

Lined with living human cells, the organs-on-chips mimic the tissue structures and mechanical motions of human organs, promising to accelerate drug discovery, decrease development costs and potentially usher in a future of personalized medicine.

The micro-devices work by recreating the tissue interfaces of human organs inside a transparent polymer “chip”, so the behaviours of bacteria, drugs and human white blood cells can be easily monitored through a microscope. A tiny channel runs through the middle, divided along its length by a porous membrane, with human lung cells on one side and blood capillary cells on the other. By running air through one side and a blood-like solution through the other, while applying a flexing and stretching motion using a vacuum, the chip can simulate the processes of breathing.

“The organs-on-chips allow us to see biological mechanisms and behaviors that no one knew existed before,” says Don Ingber, founding director of the Wyss Institute. “We now have a window on the molecular-scale activities going on in human organs, including things that happen in human cells that don’t occur in animals. Most drug companies get completely different results in dogs, cats, mice and humans, but now they will be able to test the specific effects of drugs with greater accuracy and speed.”

Ingber and his team have developed a number of different organs-on-chips to date, including a kidney, liver and peristaltic gut-on-a-chip, while skin-on-a-chip is currently in development for the cosmetics industry and for testing household cleaning products.

The different organs can also be joined up in a network, allowing the journey of a drug to be followed through a simulated human body. The effects of an aerosol drug, of the kind dispensed by an asthma inhaler for example, can be observed in terms of how it enters the lungs, how it affects the heart, how it is metabolized by the liver and how it is excreted by the kidneys, with any adverse side-effects monitored along the way in real time. Four organs have already been tested together for a two-week trial period and in two years’ time, Ingber says they will have 10 organs up and running for a month-long test. So what next? Does this work lead the way to building an artificial human-on-a-chip?

Organ On Chips is Design of the Year

Paola Antonelli, the senior curator of design and architecture at the Museum of Modern Art, added an intriguing object to the museum’s permanent collection. It was a clear plastic chip, no bigger than a thumb drive, and it could soon change the way scientists develop and test life-saving medicines.

Called Organs-On-Chips, it’s exactly what it sounds like: A microchip embedded with hollow microfluidic tubes that are lined with human cells, through which air, nutrients, blood and infection-causing bacteria could be pumped. These chips get manufactured the same way companies like Intel make the brains of a computer. But instead of moving electrons through silicon, these chips push minute quantities of chemicals past cells from lungs, intestines, livers, kidneys and hearts. Networks of almost unimaginably tiny tubes give the technology its name microfluidicsand let the chips mimic the structure and function of complete organs, making them an excellent testbed for pharmaceuticals. The ultimate goal is to lessen dependence on animal test subjects and decrease time and cost for developing drugs. Last year, researchers from Harvard’s Wyss Institute for Biologically Inspired Engineering started a company called Emulate, which is now working with companies like Johnson & Johnson on just this idea: pre-clinical trial testing. The company is currently working on incorporating Emulate’s chips into its research and development programs.

When the Harvard team first published its findings on the chips in 2010, the research was purely scientific. Now, five years later, it’s not only been inducted into the world’s foremost design collection, it’s also been named Design of the Year.

Every year, London’s Design Museum names one project as the year’s best. Past winners have included Zaha Hadid’s ethically-questionable (but stunning) Heydar Aliyev Cultural Centre in Azerbaijan, a lightbulb, and a government website. That a piece of medical equipment developed by biological engineers is this year’s winner isn’t just a nod to the design’s worthiness. It also says something about how views of what counts as “design” are changing.

To be sure, Organs-On-Chips is aesthetically brilliant. Antonelli, who recently called synthetic biology the most exciting frontier in design, described the chips as the epitome of design innovation. “In some lucky cases, the form is striking,” she says, referring to objects born out of scientific research. “In this particular case, added bonus, not only is the form striking, but so is the function—the idea behind the object.” Like a biological system, the chip’s form dictates its function, and its form is undeniably beautiful. But that’s not the end of the story. “Most people say form follows function, but it’s exactly the opposite in biology,” says Donald Ingber, a bioengineer and founding director of the Wyss Institute, which developed the chip and is working on commercializing it. “Actually, that’s not fair. It’s a dynamic relationship.” The structure of a biological system will inevitably affect the way it works, but Ingber says the design principle works both ways. “If you change the function, you can actually modulate the structure,” he says, noting how the diameter of blood vessels will adapt to decrease the tension in people who develop hypertension.

Working on the microscale requires precision. The chip effectively replaces the three-dimensional structures of an organ the renal tubules of a kidney, the alveoli of the lungs, the veins in a liver—with tissue-lined microfluidic channels. Then it emulates the mechanics of those structures. For example, running air through a channel while using a vacuum to introduce a flexing motion will simulate the patterns of human breathing. The chip’s translucent polymer, in which the channels are encased, allows scientists to see what’s happening inside organs on the microscale. The prototypes can also be linked together to form a whole-body network of organs.

Organs-On-Chips embraces the most basic of design principles: efficiency. “Design in its greatest simplicity is minimizing any system down to its elements so as to have the greatest impact,” says Ingber. Like an increasing number of researchers, he understands that good science requires an understanding of good design. The principles that govern the two fields aren’t totally separate—in fact, design is a thread that runs through every field. It’s heartening when a big award reminds us of that.

Organ on Chips Can Revolutionalize Drug Testing

It takes up to 15 years and $5 billion for a new drug to make it through testing and earn approval from the U.S. Food and Drug Administration (FDA). Before researchers try a compound on humans, it’s tested at labs in petri dishes and on animals, such as mice and monkeys. More often than not, these studies produce mixed data that don’t tell researchers much about whether it is safe and effective for humans. For some time, scientists have been searching for ways to cut down on the cost and failure rate of drug testing. Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a beautiful solution: Organs-On-Chips.The clear and flexible polymer microchips are lined with human cells. Each one represents a different human organ system, such as lungs, heart and intestines. The institute’s goal is to create 10 different organ systems that can be joined together by blood vessel channels to simulate human physiology on a microscale and provide a cheaper, more reliable way to test new drugs.

The sophisticated architecture of these organs-on-chip which are about the size of a thumb drive has also earned the Wyss Institute recognition in the art world with a Design of the Year award from the Design Museum and placement in the Museum of Modern Art’s permanent collection.“The real power of this approach is that you have a window to the inner workings of life,” says Don Ingber, founding director of the Wyss Institute and a professor of Vascular Biology and of Bioengineering at Harvard University. “Anything you can ask at the molecular level, we could do in our chips.”In 2008, the team built and tested its first “organoid” chip to mimic the mechanical function of human lungs. It contains tiny channels separated by a porous membrane to create two distinct, hollow passageways—one lined with human lung cells and the other with capillary blood vessel cells. Air is suctioned through the side channels to emulate breathing. Ingber and his team introduced bacteria into the chip’s lung channel and white blood cells into the capillary channel. They observed that the white blood cells permeated the membrane and attacked the bacteria in the lung cell channel—exactly what would happen in human lungs fighting off an infection.In another experiment, the team at Wyss filled a chip’s lung cell channel with interleukin 2, a chemotherapy drug known to cause pulmonary edema, an accumulation of fluid in the lungs. When air entered the lung cell channel, the channel filled with fluid and then blood clots exactly what happens in the lungs of patients who develop this life-threatening condition. This proved the chips could provide real world information to scientists studying the effects of new drug compounds.The project has received support from the National Institutes of Health and the FDA. The Defense Advanced Research Projects Agency also recently awarded the institute a $37 million grant to create chips representing nearly all systems in the body. Ingber says some scientists are interested in using the chips to conduct research that would be unethical if performed on people, such as studying the effects of gamma radiation on the human body.Of course, the chips have limitations. “We can’t mimic consciousness; we can’t mimic compression on a joint,” says Ingber.Danilo Tagle, associate director for special initiatives at the National Center for Advancing Translational Sciences, a division of the NIH, is spearheading a similar organ-on-chip project. He suspects that in the beginning the chips will be used to “complement and supplement” animal studies, but will eventually become routine practice. The chips will also provide researchers with information on dosing at a much earlier stage in drug studies—particularly helpful because animals metabolize chemical substances at a different rate than humans. “You can go forward with a candidate drug with greater assurance and confidence that it will have the desired effect on humans,” says Tagle. “Biology is very complex.”

Incorporating the chips into drug testing could save millions of dollars and years of time on research. Some companies are already trying out the concept. Janssen Pharmaceuticals Company, a subsidiary of Johnson & Johnson, is using a version of the chips to understand how blood clots in the lungs. The information is essential to reduce the risk for this side effect of oncology drugs. Though there still aren’t enough data to prove the chips are reliable enough to put rodents out of a job, Ingber says it’s only a matter of time; they hope to have them tested and ready for market in two years. “The FDA has been very supportive,” he says. “They’ve told us if they are as good as animals that they would consider accepting data provided by a drug company from one of these models rather than an animal model.