Virtual Body

January 19, 2016

What if you could enter a virtual world where you could travel through the bloodstream of the human body? And, what if along the way you could test a new drug on different cells to see its effect on every organ, tissue, and blood vessel? While drug testing has not advanced to the point of taking you on a Fantastic Voyage-style adventure through an Oculus Rift headset, the concept of creating a simulated environment to test drugs on live human cells is in fact a reality—and it could help make the process of testing drugs more efficient and more effective. Professor Mandy Esch and fellow researchers are developing a “body-on-a-chip.” When developing new drugs, pharmaceutical scientists often focus on curing or relieving one specific health problem and, by extension, one specific part of the body. If they aim to resolve a stomach ailment, they test their drugs on stomach cells. If it’s a problem with the lungs, they use lung cells. The problem is every organ in the body is part of a larger system that cannot be ignored. You can make the best heartburn medicine the world has ever known, but if it creates ulcers further down the digestive track, it ultimately doesn’t benefit the patient. The easy way to discover the effect a drug will have on the person is to administer the drug directly to them. Of course, this could have disastrous health consequences and is totally unrealistic and unethical. Some companies turn to animal testing to see how a drug affects different areas of the body, but few drugs that work in a lab animal’s body will fully replicate that effect in humans. “We’ve created a microfluidic system that is connected the same way as the human body,” says Esch. “With this, we’ve basically recreated the human metabolism. We are able to simulate the exchange of metabolites between all of the body’s organs. People tend to see it as a scaled-down version of the human body, but it’s more like a thin slice of the body with all of our organs represented in a system that fits in the palm of your hand.” In the device, human tissue from throughout the human body is laid out in an intricate network of channels and chambers sandwiched between two glass chips. Each channel’s thickness is determined by what is in the chamber it feeds. The channel that flows into a fat tissue chamber is quite thin compared to the channel that feeds the heart. This is to simulate the appropriate amount of blood that flows through each area of the body. Blood flow in fat is quite low, and in a heart, it is obviously high. Each chamber is also proportional to the human tissue within. Skin, the largest human organ, is given the biggest chamber while smaller organs, like the kidneys, are provided much smaller spaces. The idea is that the closer you come to the actual situation in the body, the closer you come to being able to realistically simulate drug metabolism. Suspended in a liquid cell culture that serves as a stand-in for blood, the test drug is fed through the top of the chip. It passes through the series of channels and chambers, generating metabolites from each tissue. After it has passed through once, the remaining mixture is fed back through in the opposite direction to expose every tissue to the metabolites, just as it would occur in the body. This simple technique unveils the beneficial or detrimental effect the drug has on the cells of all parts of the body. Using this novel system, unviable drug options can be detected earlier—saving time, money, and lives. Then scientists can move on to options that are more likely to achieve FDA approval and truly help people. “I’ve always wanted to do something that has an impact on society. Biomedical engineering and work like this is an ideal path for that,” says Esch. Medicines of the future will have passed this simulated human body’s tests—and virtually everyone can feel better about that. __________________________________
Esch’s team, led by Cornell’s Professor Michael L. Shuler, was recently awarded a Lush Science Prize for 21st Century Toxicology. Lush Prizes are awarded to projects and individuals that strive to replace the use of animals in product or ingredient safety testing. An additional benefit of the “Body-on-a-Chip” system is it's ability to play a significant role in determining the success of new pharmaceuticals without the use of animals. See more at: