Harvard-MIT Student Invents Humanized Mouse for Drug Development
By Marlene Taylor
Alice Chen has built a better mouse.
Since she was a girl, all things living fascinated her – from plants to pets. In science classes, she marveled at tiny pumping hearts, bean-sized kidneys, and seemingly never-ending strings of intestine. She wanted to be a doctor, or so she thought.
But Chen had other interests as well. The engineers in her family imbued her with an appreciation for tools – designing and building the right instrument for each job. When she entered college a new field -- bioengineering -- had just emerged that would allow her to combine her favorite interests.
“To me that was just the perfect blend of what I grew up wanting to do and [how] I saw myself contributing to the world,” she says.
Chen is enrolled in the Health Sciences and Technology doctoral program administered jointly by Harvard Medical School and the Massachusetts Institute of Technology.
Now, after six years of graduate research, the 29-year-old biomedical and tissue engineer is the principal inventor of a “humanized” mouse that can harbor human liver cells in its body.
To a young person, Chen would explain her work by saying, “I give mice human parts so that new drugs can be tested on mice before they are tested on people like you and me.” To the rest of us she simply says she’s a tissue engineer. The cells she implants in mice react to drugs as they would in humans, enabling researchers to determine if a drug is safe for human patients.
Chen designed an encapsulating device made of a watery substance that solidifies into the shape, size and consistency of a soft contact lens. Embedded with human liver cells, the device is implanted into a mouse’s abdomen. It is engineered in such a way as to maintain human liver cell functions, recruit blood vessels from the mouse’s vascular system and integrate with the mouse’s circulation. The encapsulating process protects the liver cells from the mouse’s natural immune defenses.
“Liver cells are really hard to culture in lab settings, says Chen. “Once they are extracted from the body they rapidly die,”
The liver is the body’s first line of defense against toxic substances and takes the brunt of unsafe drugs. Pharmaceutical companies spend upwards of $1 billion and 10 years to get one drug on the market. After undergoing years of animal trials and initiating human trials, close to 90 percent of drugs fail.
A mouse with human cells to test drugs allows researchers to know early on if a drug is damaging to the liver. Pharmaceutical researchers can then halt drug development before unsafe drugs get into the hands -- and livers -- of patients. This saves years in time, millions of dollars, and human lives.
Laboratory mice aren’t cheap. To do the kinds of studies where cells are implanted in mice, they must be immune-deficient. Maintaining these mice is extremely laborious, time-consuming, and costly. Chen can use a normal laboratory mouse as a host for her device.
Chen’s humanized mouse clears the path for other kinds of liver research, such as treatments for diseases of the liver.
Cell culture models in the laboratory are useful for early detection of liver damage from drugs, but they cannot provide information about whole body responses the way animals can. Chen’s mouse makes that possible.