Seeing Genes Express Themselves

Using magnetic resonance imaging, a researcher at Caltech discovers a way to see genes as they're being expressed in animals. He says soon it will also work in humans. Kristen Philipkoski reports from San Francisco.

SAN FRANCISCO, California -- Magnetic resonance imaging is good for looking inside our heads, spines and other body parts. Soon it might also be a tool for watching genes.

Researchers at Caltech have devised a way to watch what's called gene expression. When a gene is expressed, it's turned on. Knowing if a gene is turned on or off is one of the keys to understanding the causes of disease and eventually developing drugs.

For example, in cancer cells, the gene that tells cells to divide over and over is sometimes turned on when it shouldn't be, causing tumors to form.

Scientists now study gene expression by extracting DNA from an organism, dyeing it with a fluorescent chemical, placing it on a chip, then reading it through a scanner.

Looking at gene expression as it happens in a live animal, or in vivo, rather than after DNA has been extracted, will give researchers more robust information.

"Ways to image gene expression in vivo are important and there aren't really very many good ones," said Roger Brent, a researcher at the Molecular Science Institute in Berkeley, California. "The ability to examine gene expression in living organisms would be greatly valuable for biology as a whole."

A researcher from the Beckman Institute at Caltech demonstrated his new MRI technology at the Genome Tri-Conference in San Francisco last week.

Thomas Meade, a senior biology researcher, showed groovy three-dimensional images of frog embryos progressing from egg to tadpole. The audience could not only see the tissues of the amphibian, highlighted in brilliant red, blue and green, but also the development and communication of its cells.

It's the first time anyone has been able to see such detail using MRI. Meade and his colleagues can't yet look at gene expression in humans, because the procedure needs to be approved by the FDA.

"I'm not suggesting for a minute we can go to some poor sap and inject him tomorrow," Meade said.

But he hopes to soon replicate his frog experiment in mice.

When scientists are able to look at gene expression in mice, they will have an extremely valuable tool for researchers hoping to test drugs on humans. Mice are the top animals used in studies leading up to tests in humans, and the ability to look at gene expression in the live animal could greatly improve a drug's prospects for moving on to human trials.

Often, drugs work on stopping a particular enzyme. Meade's MRI technology could allow investigators to monitor specific enzymes in live mice.

"If you can't see the contrast agent, the enzyme ain't on and the drug is working," Meade said.

The contrast agent is the key to the technology.

Contrast agents are given to anyone who's about to have an MRI to highlight certain tissues. Usually they're made out of some variety of the chemical gadolinium and injected.

If a contrast agent shows up on an MRI where it shouldn't be, like a part of the brain, it's proof there's damage to that area. The contrast agent leaked where normally it wouldn't.

The Beckman researchers are also using gadolinium as a contrast agent, but they've specially engineered the chemical so that enzymes -- evidence of gene expression -- will light up an MRI.

In the past two years, Meade has been contacted by two researchers wanting to use his technology. After his presentation at the conference last week he had four e-mails in his inbox.

This is good news, especially since Meade and his colleagues have founded a company called Metaprobe.

It's still an embryonic effort, he said, with only six employees.

"Our mission is to commercialize this (technology) for clinical diagnostic radiology," he said.