As a kid growing up in the suburbs of the San Francisco Bay Area, I didn’t get a lot of firsthand experience with animals – mostly just the neighborhood pets and maybe a bold raccoon every once in awhile. When growing up in an urban area, loving nature requires a lot of imagination, and nothing captures a child’s imagination like Animals. We’re talking capital ‘A’, giant, ferocious, dangerous, mysterious Animals. Neighborhood dogs became vicious wolf packs, cats were solitary and deadly tigers, house sparrows were majestic birds of prey (if you squinted and tilted your head and closed one eye and completely ignored the fact that they look nothing like an eagle at all). Nothing inspired and motivated me like the big, charismatic animals and to me, working with anything smaller or less magnificent would be a waste of my time.
Which is why I think it’s pretty funny that 90% of my time now is spent looking at tiny fish that aren’t even fully developed yet. It’s a rare day when I’m not hunched over a microscope cooing over my baby fish. But to be fair, they’re not just any fish – these are special fish. They’re zebrafish.
Um… No, not quite what I had in mind. Picture by CAMEye0170 from FreakingNews.com’s photoshop competition
I use zebrafish in my Ph.D. research. I’m an aquatic toxicologist and I use zebrafish as a model organisms to investigate whether or not psychiatric drugs found in wastewater and sewage can affect the development and behavior of zebrafish, which mostly involves observing their behavior and checking out which genes seem to be important in responding to pollution stress. But that’s only one of the many, many ways scientists can, and do, use zebrafish in research.
I mean, the adults are kinda pretty? And the embryos are pretty cute. Nothing o write home about, right?
I’m sure many of you have even seen zebrafish before, in a pet store or a home aquarium. Zebrafish are originally from the Himalayan region, native to the streams, ponds, canals, and ditches of India, Pakistan, Bangladesh, Nepal, and Burma. They’re little fish (maybe a couple of inches long), they eat bugs, and sometimes can be kind of shiny. There’s not exactly a lot going for them. So why are they so special? Zebrafish are special because they are an important scientific tool that thousands of researchers around the world use to answer some fundamental questions about the life around us.
Did you know that the zebrafish was among some of the first vertebrates to ever be cloned? (Eat your heart out, Dolly!) Did you know that zebrafish can regrow parts of its body including its heart and nerves? Did you know that there are literally hundreds (maybe even thousands) of mutant strains of zebrafish kept in scientific laboratories, all around the world? And that’s just the tip of the iceberg – zebrafish are incredibly useful to biologists and have contributed countless discoveries to science.
Sometimes it takes some special effort to see how special something is. In this case, the same cutie from above, while unassuming, becomes a majestic glowing tool of science when exposed to the right kind of light. This is a genetically modified zebrafish that has a special protein called Kaede, which is a protein originally found in stony coral. Kaede normally glows green but when exposed to UV light, becomes red. This fish has had the genetic code for kaede tacked onto it’s own genes, and when we shine UV light on certain parts of its body, in this case its eyes, gut, and some parts of its tail, they glow red instead of green. Convertible glowing proteins are useful for tracking cells during development – convert just a few cells and literally follow the red cells and see where they end up!
Imagine if someone gave you a toaster, no manual, blueprint, or instructions, and told you to figure out what each part of the toaster does. The best way (at least the most fun way) to figure that out is to take it apart and then try to put it back together; take a piece out, move it around and see how that affects the toaster’s performance. That’s what zebrafish are to scientists: a living toaster. We know the different genes that make up a zebrafish, and if we want to figure out what each gene does we can go in, tinker around, and see what happens. We can remove a gene and see what happens to the fish without that gene (we call this a knockout experiment). We can take cells from one developing individual and put them into another (we call this a transplantation experiment). We can label genes, proteins, and enzymes with fluorescent proteins to help us see what’s happening – are they growing the same? Does it have all the same parts? Are there extra parts? Does something completely unexpected happen?
So it turns out when you turn off the ‘roy’ and ‘nacre’ genes, you get a transparent fish. So it’s pretty safe to assume those genes are really important in determining pigment formation. Image from Stoletov and Klemke, 2008 (Oncogene)
This is really useful because despite how different we may seem, there are lots of things that we humans share with zebrafish – many of our genes are very similar (we have about 70% of our genes in common with zebrafish!), lots of the inner workings of the body are similar, and we even develop similarly. If you look at the first couple of stages of development humans, chimps, mice, fish, and many other vertebrates all look very similar. This is a HUGE advantage for scientists since most people, for some reason, are opposed to having their genes manipulated in the name of scientific curiosity. Instead of experimenting on people, we can experiment on these fish, who produce a LOT of eggs and grow VERY quickly, and apply those results to people! We’ve learned so much about complicated conditions like cancers, neurodevelopmental disorders, and infectious diseases by studying them in zebrafish. We’ve used zebrafish to discover hundreds of drugs for countless medical conditions that have had a huge benefit to people. We’ve done so much with zebrafish that I can hardly even begin to describe them all to you in this blog, let alone in this one post!
In transplantation experiments, scientists use a very fine glass needle to take cells from a donor individual, inject them into an acceptor embryo, and then follow and observe what happens to those transplanted cells. These experiments are really valuable in helping figure out what controls cell behavior. Do developing cells already know what organs they are going to grow into or does the local environment tell them what to grow into?
Like I said earlier, I work with zebrafish and even though they aren’t as big and dangerous as a tiger or a great white shark, they have their own quiet mystery that has definitely captured me. I use them in toxicology research, but I have friends and colleagues who use them to study genetics, medicine, diseases, biophysics, and many, many other fields who all use this amazing fish to do incredible things. Stick around and I guarantee you’ll hear more about these amazing little fish.
And before we go – I’m sure you’re wondering about that weird cryptic title. I’ll just leave this here.