Those humble zebrafish swimming gracefully in your aquarium have become excellent models for studying childhood cancer and a host of other diseases.

Over the past decade they have proven to be an important tool for many areas of biomedical research, including drug discoveries, cardiovascular and neurological disease, aging and toxicology.  

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 development in the fight against drug-resistant microorganisms. Zebrafish larvae have even been used to help in the search for appetite suppressants. This involves feeding fluorescent organisms to the fish in order to quantify their feeding behavior — the more fluorescence in the larvae's stomach, the larger their appetite.

Drugs can be administered to detect possible unwanted side effects on the larvae's behavior. Nicotine, for example, was found to reduce the larvae's appetite.

Fluorescent tagging zebrafish has been employed as a powerful way to find new cancer drugs. And just recently, scientists have identified brain cells vital to how zebrafish socialize. When their neurons are disabled, orientation to one another breaks down in ways similar to socialization problems seen in humans with autism and schizophrenia.

The zebrafish, Danio rerio, is a tropical freshwater fish belonging to the minnow family (Cyprinidae) of order Cypriniformes. The popular aquarium fish frequently is sold under the trade name zebra danio. Zebrafish were originally found in slow streams and rice paddies and in the Ganges River in East India and Burma.

In the early 1970s, Dr. George Streisinger (1927-1984), a scientist at the University of Oregon, determined 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 birth rate (100 to 200 embryos per mating) and oviparous (producing eggs in which the embryo develops outside of 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’s proven use of the zebrafish in research has spread to over 300 developmental and genetic laboratories in over 30 countries. Many of the mutant strains produced in his lab are still alive in research facilities throughout the world and used to provide answers to human and animal health issues.

The zebrafish is the first vertebrate proven tractable to large-scale genetic screening formerly used so successfully in fruit flies and nematodes (worms). It has many features that make it an excellent model organism for studying development in vertebrates. The embryos develop externally to the mother and are transparent, so they can be easily viewed and manipulated. The transparency of the embryos has become one of the leading reasons for using them. Being able to see through the embryos allows researchers to watch the morphological changes that occur during development.

As mentioned above, the zebrafish has several advantages as a model for studying vertebrate developmental processes. These include small size, easy care and rapid generation time. In addition, the embryo develops from eggs that are externally fertilized. Because of their transparency, the embryos can be continuously observed under light microscopy. Mutagenesis screens can detect defects in early organogenesis and late organ function.

Because the fish is a vertebrate, its genetic program is more similar to that of mammals than invertebrate models. The evolutionary divergence of fish from the mammalian lineage occurred roughly 300 million years ago.

New studies have indicated that zebrafish can be used to discover psychoactive drugs. In the past in vitro screening assays could not be used to recreate the complex network interactions of whole organisms and thus it was not possible to predict how small molecules would alter complex behaviors. Recently discovered methods can now employ zebrafish developmental processes as a high throughput screen for small molecules that are designed to alter larval zebrafish locomotor behavior.

Recent experiments have also discovered Zebrafish’s remarkable ability to mend a damaged heart. (The hearts of zebrafish and humans both have chambers and rhythmically pump oxygen carrying blood through the body.) Mature cardiocytes (cardiac muscle cells) near the injury site detach from one another and lose their typical shape to make it possible to start dividing again to replace lost tissue. Within two weeks, the new heart tissue can receive electrical signals in the same manner as normal healthy heart tissue. Figuring out exactly how zebrafish accomplish their self-repair could help scientists find ways to trigger similar regeneration in human patients.

We can thank this tiny fish for making such a big difference to our health.

Max Sherman is a medical writer and pharmacist retired from the medical device industry. He has taught college courses on regulatory and compliance issues at Ivy Tech, Grace College and Butler University. Sherman has an unquenchable thirst for knowledge on all levels. Eclectic Science, the title of his column, will touch on famed doctors and scientists, human senses, aging, various diseases, and little-known facts about many species, including their contributions to scientific research. He can be reached by email at maxsherman339@gmail.com.