Schools of Fish Change Schools of Thought: How Zebrafish Can Help Scientists Treat Genetic Diseases

For many years, rodents have been the core of biological experiments to understand living systems and disease. We might picture mice running around, caged in rooms illuminated only by fluorescent lights. This is the image that comes into many of our minds when we hear the words “scientific experiment.” After all, rodents, like humans, are mammals, therefore many characterstics closely resemble those of people. This has made rodents an important biomedical model. But could it be in the future that small, striped, tropical fish will steal the scientific show? 

The zebrafish, Danio rerio, is a species of tropical freshwater fish native to Southern Asia in the Ganges River. Despite their small size and the fact that they aren’t mammals, zebrafish in recent years have proven extremely useful to many scientists who study rare human genetic diseases, neurodegenerative diseases and neurological disorders. Dr. Monte Westerfield, Ph.D., a professor of biology at the University of Oregon, Eugene, has been studying zebrafish as biomedical models for genetic diseases for over forty years. 

A disease is classified as a rare disease if one out of two thousand to one million people have a chronic or life-threatening condition. For a long time, there has been a gap in the knowledge surrounding treatments and therapies due to the rarity and complexity of these diseases, which is problematic for patients. Though individual diseases may only affect a small segment of the public, “rare genetic diseases” is an umbrella termthat encompasses roughly 400 million people across the globe. Zebrafish have recently become primary models in genetic similarity to humans that help scientists gain deeper understandings of these diseases. 

“Zebrafish provide an outstanding system to model human disease,” according to Dr. Westerfield. 

They contain a fully sequenced genome where nearly seventy percent of their genes are similar to those of humans, and eighty-four percent of the human genes that are found to be the culprits behind human genetic diseases have a corresponding gene in zebrafish. Zebrafish and humans share many of the same organs that perform similarly in function. In addition, human disease “behaviors” can be simulated on a larger scale by manipulating the zebrafish’s gene sequence, which is beneficial in developing treatments for some rare diseases. 

Dr. Westerfield has worked with zebrafish as biomedical models for Usher syndrome for several reasons. Usher syndrome is a rare genetic disease causing hearing impairments and retinitis pigmentosa, an eye disease that causes cell breakdown in the retina of the eye, retinitis pigmentosa (RP). 

 “Zebrafish provide excellent models to study Usher syndrome because mutations in genes that cause Usher syndrome in humans also produce the same symptoms in zebrafish,” explains Dr. Westerfield. 

Dr. Westerfield, along with other scientists in the field, use CRISPR, a gene editing technique, to modify the zebrafish genome sequence. The purpose of this genetic research is to understand the function of certain genes because the majority of human genes are still a mystery to science. By editing the zebrafish gene sequence and researching what certain genes do, scientists hope to provide more effective treatments and even cure human genetic diseases. 

Zebrafish are found in biology labs around the globe due to their ability to reproduce in a short amount of time. Their transparent embryos are also beneficial for scientific discovery allowing researchers to observe the growth of eyes, spinal cords, and hearts within two days. Another really important reason behind the popularity of zebrafish among scientists is their rare and incredibly useful capability to grow back parts of their bodies, or regenerate. Their regenerative properties extend to the retina of the eye, thyroids, fins, spinal cord, heart, and kidneys. 

Scientists find zebrafish to be particularly instrumental in advancing biological science due to their regenerative process, which allows the fish to escape cancer and even Type 1 Diabetes. Type 1 Diabetes is likely an autoimmune reaction of the body that can be worsened by hereditary genetic traits, and it destroys the beta cells in the pancreas, resulting in little to no insulin hormone production. In humans, this lack of insulin production is an issue because insulin turns sugar into energy that the body can use. Without it, the sugar builds up in the bloodstream and causes high blood pressure, among other complications. The zebrafish is, in short, unable to get Type 1 Diabetes because they have the ability to regenerate their pancreas beta cells—which are responsible for insulin production and storage. Should their beta cells fail to do their job and produce adequate levels of insulin hormone, zebrafish can regenerate their pancreas. In this case, scientists believe the differences between humans and animals may point to possible therapies.

Similarly, while degeneration of the retina is the leading cause of blindness in the Americas and Europe, zebrafish can regenerate their retinas, therefore avoiding blindness. Both humans and zebrafish grow stem cells – cells that produce different kinds of cells as a defense response to trauma or a disease. For zebrafish, this trait is incredibly advantageous because its body, as in many other species, has evolved to be able to regenerate. For humans, this special cell turns into scar tissue. Through studying zebrafish, and their astounding bodily reconstructive capabilities, scientists hope to understand what allows for and manages regeneration in zebrafish to potentially allow for regenerative abilities in humans to combat degenerative retinal diseases. 

From their genomic similarity with humans to their extensive regeneration abilities, zebrafish models help scientists study and treat a variety of diseases. And though the road is still long, medicine continues to advance due to the aid of these tiny but powerful animal models.