Fishing for clues
Leonard Zon, MD, has employed two unique weapons in his search for cures to cancer and blood disorders: 100,000 zebrafish and his own version of x-ray vision. The embryos of the tiny vertebrates that fill hundreds of fish tanks in Zon's lab are transparent as they develop and grow outside the mother's womb, allowing Zon to "look through the window" and observe the body's internal workings as they develop.
A Howard Hughes Medical Institute investigator and hematologist/oncologist, Zon chose the zebrafish because it has many genetic characteristics in common with humans, and may be able to help him solve the mysteries of the blood disorders and cancers he studies.
"The human genome is roughly twice as large as that of the zebrafish, but the genes are positioned in a similar place," says Zon, who likens these genomes to three-dimensional maps. Additional benefits of zebrafish are that thousands can fit into a contained space and female zebrafish produce nearly 300 offspring every week, allowing researchers to genetically alter and study many generations of families in a relatively short period of time.
Through the process of mating mutant zebrafish and analyzing their offspring, Zon and his colleagues have found three blood diseases—two types of anemia and one form of thalassemia—which are very similar to those found in humans. They also have identified embryos that display the abnormal cell division responsible for different types of cancer.
Zon's efforts have propelled the little tropical fish into the spotlight. Three years ago he asked the National Institutes of Health (NIH) to fund a zebrafish genome project. It responded with $5 million in funding for each year of the grant from the NIH. Additionally, the Sanger Center in England, a key contributor to the sequencing of the human genome, has taken on the zebrafish genome as its next challenge. Once it is decoded, the difficult work of finding genes responsible for specific diseases will be accelerated.
Until then, Zon will continue checking his human map against that of the zebrafish, looking for the X that marks the spot, and seeking treatments for some of today's most devastating diseases.