Casper the Friendly Cancer-Fighting Zebrafish

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We all know Casper as the Friendly Ghost who flies around with Wendy. But what does this lovable ghost have to do with finding new cures for cancer?

The answer is zebrafish. For years, scientists have been using zebrafish as model organisms for a variety of different conditions, such as growth and development, neurodegenerative disease, and diabetes (Heath, 2013). Since they are small and reproduce quickly, they are ideal for keeping in a lab (Heath & White, 2013). Additionally, they are perfect for studying development, as their eggs grow outside of the mother (unlike mice), but are still vertebrates and, thus, are similar to humans.

Zebrafish are naturally transparent during the embryo and larval stages (Heath & White, 2013), but scientists have now taken this transparent property one step further. Typically, as zebrafish larvae grow and develop, they gain pigmentation. Dr. White and his research team at Boston Children’s Hospital have stopped this pigmentation by “knocking out” specific genes, keeping adult fish transparent (White, 2008). THis is useful for watching how the fish, and tumors, develop. The heart, brain, lateral vessels, and intestinal tube can be easily seen in these clear fish (White, 2008).

Casper zebrafish. Photograph courtesy of Dr. Paul Frankel  (University College London) and Prof. Paul French (Imperial College London).

Casper zebrafish. Photograph courtesy of Dr. Paul Frankel (University College London) and Prof. Paul French (Imperial College London).

The new zebrafish was playfully named after the friendly cartoon ghost. This development opens up many new areas for study since more diseases affect adults than children; the model allows researchers to see development into the adult stage. Their transparency allows scientists to monitor a disease without having to harm the organisms. This means that scientists can watch long-term progressions of illnesses. Recently, the focus has shifted to cancer research.

The Ideal Model Organism

What are the qualities of an excellent model organism? One that is small, inexpensive, and similar enough to humans to model diseases; one that easily replicates for additional trials; and one that contracts the same disease of study in a similar manner as humans.

These are some of the many reasons that the zebrafish, or Danio rerio, is seen as an ideal model organism for cancer research. They are small and, thus, many can be tested in small lab spaces. They also reproduce weekly and produce 100-200 embryos each time they mate (Heath & White, 2013).

Cancer-Fighting Fish

One in two men and one in three women will develop cancer in his or her lifetime (“Lifetime Risk,” 2012). Everybody probably knows someone who has suffered from the disease. Cancer does not have a singular cause. It can appear in various places throughout the body and develops differently based on where it is located. Some cancers have a genetic component, while others are purely the result of environmental factors. However, all involve out-of-control cell growth (“What is Cancer?”, 2012). Much progress has been made in recent years involving understanding this disease and finding new treatments. However, we are still a long way from eradicating cancer.

Scientists now believe that the Casper zebrafish may hold the key to gaining a better understanding of how cancer moves and changes, which could provide insight into how to create better treatments. Scientists were even able to inject the fish with pigmented melanomas and watch the cancer grow and metastasize (Heath & White, 2013).

A zebrafish with a tumor (red). Photograph courtesy of Dr. Paul Frankel (University College London) and Prof. Paul French (Imperial College London).

A zebrafish with a tumor (red). Photograph courtesy of Dr. Paul Frankel (University College London) and Prof. Paul French (Imperial College London).

Additionally, cancers can be purposefully triggered by slight changes in a fish’s genes. Researchers are now able to easily microinject early stage zebrafish embryos with the gene of interest in the form of DNA or mRNA. The fish then grow and develop and can pass on the injected gene to the next generation (Heath, 2013). This technique could be used to examine the genetic component of cancer or other hereditary conditions, such as Alzheimer’s or Inflammatory Bowel Syndrome (IBS) (Newton, 2008).

Another feature of these magical fish is that they develop cancer is the same way that humans do. Cancers in zebrafish “often share common genetic underpinnings” with human versions of the disease (Heath & White, 2013). Zebrafish also develop specific cancers in the same areas that humans do. For example, a tumor of intestinal cancer would develop in the fish’s gut just as it would in a human’s. This makes studying patterns of growth easier, as scientists know where to look for the cancer, and gives a more accurate idea of how the fish’s cancer relates to its human counterpart.

A Cure For Cancer?

As of now, this new model organism holds great promise for the future of cancer research. There are only a few possible disadvantages to using Danio rerio as a model organism. First, as with all model organisms, they are not physiologically identical to humans. Additionally, some genes have more than two copies, making it difficult to determine genetic functions or correlations (Ali, Champagne, Spaink, & Richardson, 2011).

And although there will probably never be an umbrella panacea for all cancers, scientists seem to be heading in the right direction. Hopefully, by using research tools like the Casper zebrafish, we may be much closer to finding future treatments and cures for a wider variety of cancers. Maybe one day, curing cancer will be as easy as waving Wendy’s wand.

Works Cited

In Brief:

  • Both men and women have a high risk of developing some form of cancer during their lifetimes
  • Zebrafish are ideal model organisms for developmental studies because their embryos are transparent
  • Researchers at Boston Children’s Hospital have developed a transparent mutant zebrafish commonly known as the “Casper” zebrafish that allows scientists to watch cancers develop in adult fish

This article was written by cYw9. As always, before leaving a response to this article please view our Rules of Conduct. Thanks! -cYw Editorial Staff

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Horses, Hounds, and Research Highlights: An Interview With Dr. Lance Perryman

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Dr. Lance Perryman, who contributed to the discovery that Severe Combined Immunodeficiency (SCID) is inherited as an autosomal recessive condition in Arabian horses, recently took the time to share some insight with curiousYOUNGwriters (cYw).

As was stated in our feature piece on SCID, “Arabian horses aren’t being utilized for research purposes as often as their benefits suggest,” and Dr. Perryman could offer some reasons as to why this is the case.

Despite his groundbreaking work with SCID, Dr. Perryman didn’t get started researching the disease until after receiving his PhD from Washington State University.

Despite his groundbreaking work with SCID, Dr. Perryman didn’t get started researching the disease until after receiving his PhD from Washington State University.

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Weave Come A Long Way: The European House Spider’s Webs May Hold the Answers to Aging

We all get older.  We are all constantly aging.  Every minute of every day we are getting closer to our deaths.  This may sound depressing, but scientists have recently been using spiders to unlock hidden clues to the aging process.  Could it be possible that the keys to staying young may be written in their webs?

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Current Research: Leprosy Bacterium Unchanged

A recent study of leprosy‘s genome verifies the old adage: “some things never change.”

An international group of researchers has extracted bacterial DNA from the skeletons of 24 leprosy victims in the hopes of finding genetic changes that led to leprosy’s declining prevalence. The samples that the team collected were compared to bacterial samples from current leprosy patients living in India, Thailand, the United States, and Brazil.

And what did the researchers find?

“…No meaningful differences,” according to Stewart Cole of the Swiss Federal Institute of Technology in Lausanne and a member of the research team. Because leprosy hasn’t changed much over the past few hundred years, Cole and the rest of the research group have speculated that the disease’s decline may have been due to social isolation of lepers or the rise of other diseases like the plague and tuberculosis.

Check out the full story here!

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Fly Genes of the Past: The Future of Cancer Research?

Rachel Kim, an ordinary young girl who loved to swim, was looking forward to her upcoming second birthday.  In June 2003, she awoke one day with a fever that lasted for two whole weeks.  Rachel began to complain of leg pains and her family noticed that her stomach was distended.

One month later, when the Kims took Rachel to the pool, she uncharacteristically cried and refused to play.  Suspecting that something was wrong with their daughter, the Kims took Rachel to her pediatrician who reported a shocking diagnosis.  Rachel had neuroblastoma.

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Current Research: Lighting the Way for Muscular-Dystrophy Research

What if a method of determining the severity of muscular dystrophy lies within a familiar summertime insect?

Scientists at Stanford University School of Medicine have recently created a mouse model of the disease in which degenerating muscle gives off visible light- using the same protein that allows fireflies‘ tails to glow. This precise technique causes luminescence to occur in direct proportion to the amount of damage the muscle has sustained. So, not only will a damaged muscle “glow,” but the more damaged the tissue is, the more it will glow.

Here’s how it works: Under normal conditions, a rare class of stem cells, called “satellite cells,” sit quietly next to muscle fibers. But under abnormal conditions, such as muscular injury or degeneration, these satellite cells divide and integrate themselves into the damaged tissue, repairing the muscle. The Stanford team, under Thomas Rando, created an experimental mouse strain in which an inserted gene for luciferase, or firefly-glow-protein, is activated only by satellite cells.

Once a luciferase gene is “turned on” in a mouse’s satellite cell, it remains “on” for the rest of the mouse’s life and is passed on to its progeny as well. Luminescence is shown by giving the mice a compound that gives off light in the presence of luciferase.

“In these luminescent mice, we could pick up the disease’s pathological changes well before they could be seen otherwise,” says Rando. “The readout was so sensitive we could observe those changes within a two-week period. Not only that, but we got our measurements instantaneously, without killing the mice.”

Although this technique is not yet applicable to humans, it holds promises for quicker, cheaper, and more accurate assessments of muscular dystrophy drugs.

Check out the full story here and Rando’s original paper here!

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