Researchers at Children's Hospital Boston's Stem Cell Program have bred a transparent zebra fish to help them better understand disease processes by seeing them.

Zebra fish are genetically similar to humans and good models for human diseases like cancer.

However, it is difficult for researchers to view the effects of interventions or medications without having to kill and dissect the animal.

Zebra fish embryos are transparent, enabling researchers to study disease in live organisms. But after about 4-5 weeks old, the adult fish are opaque.

By creating a fish that is transparent throughout its lifetime, researchers can directly view its internal organs and observe disease processes like tumor growth or the grafting of bone-marrow transplants.

‘Casper’ was created by Dr Richard White, a clinical fellow in the Stem Cell Program at Boston Children’s, with others in the laboratory of Dr Leonard Zon.

Human diseases are generally studied in animals by giving the animal the disease, then killing and dissecting it to discover what the disease did.

But in cancer and other fast-changing processes, this method is bound to miss something, White says

“It’s like taking a photograph when you need a video.”

Fluorescent Melanoma Tumor

White’s first experiment with Casper involved creating a fluorescent melanoma tumor in the transparent fish’s abdominal cavity.

Viewing the fish under a microscope, he 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’ on 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.”

Stem Cell Transplants

The transparent fish may also answer questions about how stem cell transplants work.

Transplants of blood-forming stem cells help cancer patients rebuild healthy blood, but some transplants don’t ‘take’, for reasons that are unknown.

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.

Creating a Transparent Fish

White created the transparent fish by mating two existing zebrafish breeds.

Zebrafish have three pigments in their skin—reflective, black, and yellow.

He mated a breed that lacks reflective pigment with one that lacks black pigment.

The offspring had only yellow pigment in their skin, essentially looking clear. White named the new breed ‘Casper.’

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

White says this tool could provide insight into how mutated genes cause diseases ranging from Alzheimer’s disease to inflammatory bowel disease.

The development of Casper is described in the February 7 issue of Cell Stem Cell,

The Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, with more than 500 scientists,

Fluorescent Green Blood

The useful zebra fish has undergone another makeover by scientists in the name of medical research – fluorescent green blood vessels.

The genetically modified zebra fish are assisting Indiana State University assistant professor of life sciences Allan Albig work out how to stop blood vessels from growing towards cancer tumors, a process called angiogenesis.

Once tumors access the bloodstream, they can grow and spread to other locations within the body by metastasizing.

Albig’s research centers upon identifying molecules in extracellular spaces that regulate blood vessel growth and could be converted into anti-angiogenesis or anti-cancer medicines.

He and his students are working through a list of genes to discover which ones are used in blood vessel growth.

The fish have been genetically altered to have fluorescent green blood vessels, which easily show up under a microscope and help Albig and his team monitor their growth.

“If we can figure out how to stop blood vessels from growing toward tumors, we might be able to stop tumors from becoming cancer.” he says.

“It probably isn’t going to kill the tumor altogether, but the idea is that if you can shrink tumors and stop tumors from metastasizing, you can manage the disease.”