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.
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.