Caspar the see-through fish

Source: Children's Hospital Boston

Researchers at Children's Hospital Boston have created a transparent zebrafish, allowing them to directly view its internal organs and observe processes like tumour metastasis and blood production after bone-marrow transplant.

The fish, described in the February 7 issue of Cell Stem Cell, was created by Dr Richard White, a clinical fellow in the stem cell program at the hospital, and colleagues in the laboratory of Dr Leonard Zon.

Zebrafish embryos have enabled researchers to study disease in live organisms as they are transparent, but adult zebrafish are opaque.

"Everything after four weeks has been invisible to us," White said.

White's first experiment on the zebrafish examined how a cancer spreads. He transplanted a fluorescent melanoma tumour into the fish's abdominal cavity and watched as the cancer cells begin to spread within five days.

He even saw individual cells metastasise, 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 tumour cells spread to other parts in the body, they don't do it randomly," White said. "They know where to go."

White plans to study tumour cell homing, then look for ways to modify the tumour cells or cells of the host so that the spreading cells never find their new location.

Another experiment involved transplanting green fluorescent protein-labelled haematopoietic stem cells and watching them engraft.

By four weeks, the fluorescent stem cells had visibly migrated and grown in the fish's bone marrow. Even individual stem cells were visible, White said.

The team created the transparent fish simply by mating two existing zebrafish breeds.

Zebrafish have three pigments in their skin - reflective, black, and yellow. White mated 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. White named the new breed "Casper."

The fish's brain, heart, and digestive tract are also visible, allowing researchers to study genetic defects of these organs from early embryonic development through adulthood.

White hopes this tool will provide insight into how mutated genes cause diseases ranging from Alzheimer's disease to inflammatory bowel disease.