Glowing Fish Warn of Danger
ARRA Success Story
Lisa Satterwhite, Ph.D.
In a lab at Duke University, Lisa Satterwhite, Ph.D., is working to create some very special fish. Satterwhite's fish will act like a signal flare, flashing in the presence of dangerous toxic chemicals. Satterwhite recently spoke about her passion for science and how a photograph of a baby changed her research and her life.
Early development in humans is enough like fish where this is practical research.
Satterwhite: "A few years ago, I was reading the paper and saw a picture of a baby born without arms or legs. He was the child of a migrant farm worker, and his story had a profound effect on me. I wanted to learn more and discovered that the mom had probably suffered from overexposure to pesticides during pregnancy. I was stunned to learn that in one growing season, there were 14 pesticides used on the tomato fields where she worked.
"We're creating a strain of tiny zebrafish that will glow to signal toxicity of pesticides in various combinations. The ARRA funding has let me keep my job and continue my exciting research!"
- Lisa Satterwhite, Ph.D.
I wondered if my background in cell biology might help me prevent future birth defects like this. I have studied cell division for a long time, especially what causes cells to divide so that chromosomes are separated properly so that development is normal.
My research, funded by a Recovery Act grant from NIEHS, involves developing zebrafish embyros to signal when pesticides might interrupt heart and limb development, both of which develop initially in the first trimester. Early development in humans is enough like fish where this is practical research. One of the beautiful things about life on earth is that it develops in very similar ways -- all vertebrates develop using the same processes and biochemistry. That lets us study another vertebrate and get relevant predictive information that will apply to humans.
The process I use is pretty simple: expose cells from an organ to a toxin; see what genes change; then, design a fish to carry that gene in fluorescent form. Then you have a fish that will visibly signal to you when that gene product becomes prevalent.
Pesticides are added to the water of developing fish embryos. We have many tanks, so we can do this with any single pesticide or combinations. If it causes a change in the gene we're targeting, there will be a flash of light. In other words, the fish can signal what is happening at a genetic level.
When we exposed zebrafish embryos to pesticides in the lab we saw defective heart ventricles in the fish, so now we have an experimental system that will allow us to study a specific heart defect. Additionally, I’ve found patterns of genes affecting major biological pathways that respond to pesticide exposure. For example, several genes are in a group that are mutated in asymptomatic sudden cardiac death in humans. Other genes affected by pesticides are in a class of tumor suppressor that are the same as those lost in breast cancer. It turns out, pesticide exposure induces expression of this protein. So, another goal I have is to make fish strains that signal when these tumor suppressor pathways are activated, and hopefully they will be predictors for risk of cancer. That will help us determine whether pesticide exposure leads us to be more susceptible to developing cancer and other diseases later in life.
Testing these scenarios in a way that's relatively easy and predictive of risk makes a lot of sense.
I want to offer this as a new testing paradigm - so government and industry can test combinations of chemicals. Right now only single pesticides are tested, and the tests used are not predictive of developmental abnormalities, particularly in the combinations of pesticides that are used and to which we are exposed. So, in the tomato field where many pesticides were used, it could be that two or more of these could have 10 times the potency. On the other hand, it could be something like sequence -- maybe one is OK, but a couple weeks later, when the second pesticide is added, now you’re in major trouble. Testing these scenarios in a way that’s relatively easy and predictive of risk makes a lot of sense."