A Transparent Fish for Studying Cancer

A transparent zebrafish will allow scientists to study the spread of cancer and other biological phenomena.
Image courtesy of Richard White

Zebrafish embryos are a staple of developmental biology: the transparent eggs allow scientists to study development as it unfolds. The adult fish, however, are opaque, making them less tractable as a model organism.

Now scientists at Children's Hospital Boston have generated a transparent zebrafish by mating two specific strains: a breed that lacks reflective pigment, called roy orbison, with one that lacks black pigment, called nacre. The offspring had only yellow pigment in their skin, essentially looking clear. Richard White, a clinical fellow in the Stem Cell Program at Children's, named the new breed Casper, according to a press release from the hospital.

The animal will allow scientists to study tumor formation in action. In a study published in the journal Cell Stem Cell, White, along with others in the laboratory of Leonard Zon, created a fluorescent melanoma tumor in the transparent fish's abdominal cavity. Here is an excerpt from the press release:

Viewing the fish under a microscope, White saw the cancer cells begin to spread within five days. He even saw individual cells metastasize--something that has not been observed so readily and in real time in a living organism.

The spreading melanoma cells appeared to "home" to the skin after leaving the abdominal cavity. "This told us that when tumor cells spread to other parts in the body, they don't do it randomly," says White. "They know where to go."

The fish may also answer questions about stem-cell transplants. While transplants of blood-forming stem cells help cancer patients rebuild healthy blood, some transplants don't "take," according to the press release, for reasons that are unknown. Scientists have lacked a full understanding of what steps blood stem cells must take to do their job, says White. He showed that the process is observable in the fish. He first irradiated a transparent fish's bone marrow, then transplanted fluorescent blood-forming stem cells from another zebrafish. After four weeks, the fluorescent stem cells had visibly migrated and grown in the fish's bone marrow, which is in the kidney. Even individual stem cells were visible--something that researchers haven't easily observed in a living organism, White says.

By studying how the stem cells embed and build blood in the fish, scientists can look for ways to help patients rebuild their blood faster. Drugs and genes could be tested in the living fish, with direct observation of results, White says.