Zebrafish: a Living Window

Zebrafish: a Living Window header image
Tiny see-through fish offer a model for understanding human health.

There’s a fish out there that might hold the secret to why some people get
cancer and why some don’t. A fish that is mostly transparent for the first
ten days of its life, allowing researchers to watch as its organs form and
its body develops. As a window into human health, scientists credit Danio rerio
– zebrafish.

In a Petri dish the size of a saucer, 20 fertilized fish eggs rest in cool
fresh water. They are round bubbles, milky looking but see-through. A female
zebrafish, about the size of a standard office paperclip, laid the eggs this
morning; a male zebrafish fertilized them seconds later.

Before the parents can eat the eggs, which are incredibly high in protein,
researchers collect them from their specially made tanks at Oregon State University’s
Sinnhuber Aquatic Research Laboratory
. Researchers then count the eggs and
parcel them out to different studies that range from uncovering causes of childhood
disease to the impact of common chemicals on muscle and nervous system development
in human children.

“Many human diseases can be modeled in zebrafish,” says Robert Tanguay, an
OSU College of Agricultural Sciences professor and director of the Sinnhuber
lab. “With about 80 percent of genes in humans also present in these fish,
they present an opportunity to better understand risks that chemicals pose
to human health.”

By this afternoon, the developing eggs will have taken on a slightly different
shape. Their eyes will begin to take form. By lunchtime tomorrow, they will
have beating hearts. Another 24 hours and the fish will be swimming. Blood
will be flowing through tiny circulatory systems.

“It’s the same process that occurs in developing humans,” says Tanguay. “But
it’s much faster. It’s a difference between hours and weeks.” Zebrafish, which
are commonly sold in pet stores for home freshwater aquariums, have been used
for research at OSU since the mid 1990s, and used worldwide in medical research
programs for more than 30 years.

At the Sinnhuber lab, researchers capture about 25,000 eggs each day for studies
related to human health. These studies explore questions like, “What are the
implications of pesticide exposure on developing organisms, including human
embryos?” or, “Is the mental disease schizophrenia caused by environmental
exposure to chemicals during development?” The rapid developmental rate of
the eggs means that researchers can run many tests in a short time on a huge
number of subjects. And that means that answers can be found, not over the
course of decades, but in months and weeks. As a result, scientists from around
the world use zebrafish to study genetics, human health, and the development
of vertebrates.

zebrafish photo by Lynn Ketchum
Much of the work Robert Tanguay's group does with zebrafish is transferable to humans. Photo by Lynn Ketchum.

Back in the lab, Britton Goodale, an OSU graduate student, is studying how
poly aromatic hydrocarbons (PAHs) interact with, and possibly disrupt, normal
vertebrate development. In some cases, PAHs are a significant toxicological
health concern. They can be produced in the environment by both human and natural
events. Sources of PAHs can include vegetation; geological processes including
seeps, coal outcrops, crude oil spills and the release of fossil fuels; and
the high temperature combustion of organic materials, as in the case of forest
fires, car exhaust and the burning of wood stoves.

Goodale uses a long, very slender, very delicate needle to inject small amounts
of PAHs into the zebrafish eggs. She will observe the eggs over the next few
days as they develop into larvae. During this stage, the larvae do not yet
need to eat and the researchers have ultimate control over their developmental
conditions. Goodale will watch for early developmental markers that signal
PAH exposure. PAHs have the capacity to cross the placenta during early vertebrate
development, but it is not yet known how, and at what level, they affect embryo
development. This work may help to close that gap in knowledge, says Tanguay.

Much of the work done with zebrafish is transferable to humans. From offering
clues to human deafness, to helping determine how a heart might heal itself
after cardiac arrest, the tiny fish are helping to enhance medical knowledge
that benefits human health and wellbeing. Jill Franzosa, a PhD candidate in
the lab, is using zebrafish in early developmental stages to study the impact
of aging on tissue regeneration. Her work could improve therapies for the restoration
of individual cell types and tissues in humans.

The National Institutes of Health and the National Institutes of Environmental
and Health Sciences have granted the Tanguay group over $1 million in funding
this year alone to train new researchers in the use of aquatic models, like
zebrafish, and to use them to develop new studies related to the effects of
environmental exposure to chemicals, nanomaterials, and pharmaceuticals on
human health. Tanguay is also working to understand how to translate results
from zebrafish to humans to help promote tissue replacement following disease
or injury.

“We have a defined goal: to understand the ways in which a specific chemical
or substance causes harmful effects to living things, and then to use that
information to protect humans and the environment,” says Tanguay. “Our ability
to learn from the studies conducted in the lab relates directly to our goal
to prevent diseases and illnesses that plague our families and communities.”

A tiny fish egg sits under a microscope. As a researcher watches, organs develop,
a heart begins to pump. A tiny syringe carrying a chemical common in the human
environment pierces the embryo. A shift occurs. A discovery is made. A life
is changed.

Published in: Health