A Window into the Heart ... and Everything Else

The clear fish allows researchers to track the migration of the tumor cells, which look like black dots in this picture. Courtesy of Richard White

Friday, February 29th, 2008--

Hidden behind skin and scales, many biological processes--how cancer spreads and how stem cells travel for example--have remained largely invisible to us. Now researchers have provided a window, a tool that reveals the inner workings of a living organism--a transparent fish.

Dubbed "Casper", the clear fish is a cross between two zebrafish strains that have pigmentation mutations. Richard Mark White and Leonard Zon of Children's Hospital Boston, the Dana Farber Cancer Institute and Harvard Medical School in Boston, MA and colleagues described their see-through zebrafish in the journal Cell Stem Cell.

Why is it important to observe cells in their natural habitat? Cells, like the animal they make up, are affected by the environment in which they live. "When you study a particular cell type, let's say it's a stem cell, the way it interacts with its environment is really important," says White, a clinical fellow in the Stem Cell Research Program at Boston Children's Hospital.

The hope is that by watching diseases like cancer, or treatments like stem cell therapy as they happen in the body, scientists will be able to identify environmental triggers that affect the behavior of the cells. "What you lose in a dish are these exceedingly complex environments," White says. "In a best case scenario, I can take a cancer cell and grow it next to another type of cell, but I can't recreate the incredibly complex environment in which the cancer cell grows inside the body."

White has already started to watch what happens when cancer spreads (called metastatic disease). One preliminary finding is that the movement of cancer cells may not be random, White says. If researchers can decode the pattern for how cancer moves and why it settles in some parts of the body but not others, scientists may be able to identify chemical treatments that interrupt that movement.

Leonard Zon, the director of the Stem Cell Research Program at Boston Children’s Hospital, says that this fish may also provide new insight into stem cell therapies, like bone marrow transplants. "Basically I appear at the bedside with a bag of bone marrow and then [I] infuse it into somebody's veins. The cells need to travel throughout the blood vessel systems and then land in a place where blood cells are formed, which turns out to be inside the bones," Zon says. The question is: how do the cells know where to go? Tracing the exact route of stem cells may help Zon understand why cells get to the right place, and why they amplify once they reach their destination. Understanding what triggers these processes could improve transplant success.

"Every time we look at the marrow in particular, we can't help be struck that this is a process that clearly depends on the cells themselves but also very clearly depends on the environment that they're in," says White. "Both of those are therapeutic opportunities."

--Flora Lichtman