Washington, Feb 7 : Researchers at Children's Hospital Boston have created a zebrafish that is transparent throughout its life and hence could be used to examine various human processes.
Zebrafish, being genetically similar to humans, prove to be good models for human biology and disease.
The new fish created by Richard White, MD, PhD, a clinical fellow in the Stem Cell Program at Children's, with others in the laboratory of Leonard Zon, PhD, may allow scientists to directly view its internal organs, and observe processes like tumour metastasis and blood production after bone-marrow transplant in a living organism.
According to Dr. White, this breakthrough may just out do the classical method of killing and dissecting the animal after allowing it to get the disease. He said that while Zebrafish embryos may enable the researchers to study disease in live organisms, since they are transparent, but zebrafish adults are opaque. His first experiment on the zebrafish examined how a cancer spreads.
"The process by which a tumour goes from being localized to widespread and ultimately fatal is the most vexing problem that oncologists face. We don't know why cancer cells decide to move away from their primary site to other parts in the body," said White.
He created a fluorescent melanoma tumour in the transparent fish's abdominal cavity. When he viewed the fish under a microscope, he saw that 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. He also observed that after leaving the abdominal cavity the spreading melanoma cells appeared to "home" to the skin.
"This told us that when tumour cells spread to other parts in the body, they don't do it randomly. They know where to go," said White.
White is also hoping to study tumour cell homing, and later look for ways to modify the tumour cells or cells of the host so that the spreading cells never find their new location.
Zebrafish may also be useful in uncovering the mystery about stem cell transplants. White said that while transplants of blood-forming stem cells help cancer patients rebuild healthy blood, some transplants don't "take," for unknown reasons. Scientists have lacked a full understanding what steps blood stem cells must take to do their job.
He demonstrated that the process can be observed in fish. First, he irradiated a transparent fish's bone marrow, and then transplanted fluorescent blood-forming stem cells from another zebrafish.
After 4 weeks, the fluorescent stem cells had visibly migrated and grown in the fish's bone marrow, which is in the kidney. White said that even individual stem cells were visible, something researchers haven't easily observed in a living organism.
He also said that scientists can look for ways to help patients rebuild their blood faster by studying how the stem cells embed and build blood in the fish. Drugs and genes could be tested in the living fish, with direct observation of results.
White created the transparent fish simply by mating two existing breeds of zebrafish. These fish have three pigments in their skin-reflective, black, and yellow.
He mated a breed lacking 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 is positive that this tool will provide insight into how mutated genes cause diseases ranging from Alzheimer's disease to inflammatory bowel disease.
"What happens in a living organism is different than what happens in a dish," said White.
The study is published in the latest issue of Cell Stem Cell.