From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 156
Over the past decade, zebrafish have become an important tool for many areas of biomed-
ical research, including cancer biology, drug discoveries, cardiovascular disease, aging and
toxicology.
Much of this information can be found in a journal devoted solely to zebrafish
research.1 Zebrafish combine ease of reproduction with versatility, adaptability and simi-
larities to humans that make them something of a small wonder to researchers.
An outstanding recent example of just how valuable this animal is came when the
“gold standard” USP cytotoxicity assay using live mouse fibroblasts (L929) cells in culture
failed to detect the toxicity of a BPA (bisphenol A) extract during testing, while the new
zebrafish embryo screen did.
Zebrafish hearts are being studied because of their remarkable repair work. When a
zebrafish heart loses up to 20% of a ventricle, it forms a clot that stops the bleeding, and
then the heart gradually replaces all the lost tissue.2 These finned wonders have also been
used to study thalidomide’s devastating effects on fetal development.3
The growing interest in using zebrafish for genetic and functional dissection of malig-
nancy and infection was highlighted by the second international workshop on Zebrafish
Models of Cancer and the Immune Response in Spoleto, Italy, in July 2009. The theme of
the meeting was the unique suitability of zebrafish for in vivo monitoring of fundamental
biologic and pathologic processes.
It was reported that in vivo monitoring can be instrumental for developing disease
models of solid tumors, leukemia and inflammatory conditions. Monitoring can also be
used to assess the efficacy of small molecule drugs under physiologic and pathologic
conditions.4
Zebrafish models of infectious diseases such as tuberculosis have been established
that are now amenable to high throughput in vivo drug screens, a much-needed develop-
ment in the fight against drug-resistant microorganisms.5 This article describes zebrafish,
provides a brief history, discusses how and why zebrafish are utilized, and concludes with
regulatory issues.
Description
The zebrafish, Danio rerio, is a tropical freshwater fish belonging to the minnow family
(Cyprinidae) of order Cypriniformes. It is a popular aquarium fish, frequently sold under
the trade name zebra danio.6
Zebrafish were originally found in slow streams, rice paddies and in the Ganges River
in East India and Burma. Its name derives from the striped coloration of its body.
History
In the early 1970’s, Dr. George Streisinger, a scientist at the University of Oregon, deter-
mined that the zebrafish was an ideal model for studying vertebrate development and
genetics. Streisinger is considered by many of his peers as the founding father of zebrafish
research.
He recognized that the short generation time of the zebrafish (two to three months),
its high fecundity (100–200 embryos per mating) and oviparous (producing eggs in which
the embryo develops outside the maternal body) mode of reproduction were ideally
suited for the rapid screening of the progeny of mutagenized fish for mutations that affect
important developmental processes. Streisinger focused on how genetic mutations affect
nervous system development in lower vertebrates and, in 1981, published a method using
zebrafish that allowed screening for mutants among parthenogenetic (nonsexual repro-
duction) offspring of mutagenized females.7
His proven use of the zebrafish in research has spread to more than 300 developmen-
tal and genetic laboratories in more than 30 countries, and many of the mutant strains
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