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When you look at a zebrafish, you probably just see a cute, tiny fish that's smaller
than your pinky finger.
But this little fish is so much more than that.
You're looking at an amazing scientific tool that has led to some major discoveries.
Zebrafish have been used since the 1970s to study the development of vertebrates, and
more recently, they've been helping scientists learn more about human diseases and maybe
even develop some potential treatments.
So why the zebrafish?
Well, like all fish, their genomes are similar to the human genome, mainly because we share
a common ancestor.
They have over 26,000 protein-coding genes, and about 70% of those genes are related to
similar genes in humans.
Since zebrafish have been studied so much, we know that around 80% of the disease-causing
genes that have been identified in humans have at least one related gene in zebrafish.
By studying what these genes do in zebrafish, scientists can learn more about what they
do in humans.
And there are other reasons researchers specifically study zebrafish:
They're cheap to maintain, and the females can spawn around 200 to 300 eggs in a single
week, which makes for a lot of new test subjects.
More importantly, zebrafish embryos and larvae are transparent and develop really quickly.
There's even a genetically-engineered strain of zebrafish that's transparent through
its whole life.
That transparency allows researchers to see exactly what's going on inside the fish's
body, and watch biological processes — like how cancers develop.
That said, zebrafish still aren't the perfect model for human disease — for one thing,
they don't have lungs or mammary glands.
Plus, a lot of their genome is made up of duplicate genes.
Some of those gene copies might have mutated and developed functions that weren't there
in the ancestor's gene — which would make them different from the human versions.
Even so, zebrafish have been able to help scientists learn about a lot of different
diseases -- like melanoma, the most dangerous type of skin cancer.
Cancer develops because of mutations in specific genes that affect how cells multiply and die.
And the most common mutation related to the melanoma is called BRAF(V600E).
Zebrafish that carry this mutation, and also lack a tumor-suppressing gene, make good models
for the disease.
So researchers can study how cancer develops in fish with the BRAF mutation, and use them
to test treatments.
They've also used zebrafish to find other melanoma-causing genes.
See, sometimes, the BRAF mutation just causes benign moles instead of melanoma.
BRAF might start the process, but another gene has to cooperate to actually cause the
melanoma.
The question was how to find that gene.
The researchers used human melanoma samples to look for duplicated genes that might cause
cancer along a certain section of a human chromosome.
The duplicated genes they found were then inserted into the genomes of zebrafish with
the BRAF mutation.
And only one gene, called SETDB1, was found to accelerate melanoma formation in the zebrafish.
This discovery might lead to the creation of new cancer therapies that target SETDB1.
Zebrafish research might also be able to help with stem cell transplants.
And the reason for that has to do with a compound called prostaglandin E2.
In a study, researchers discovered that when certain chemicals were used to enhance prostaglandin
E2 synthesis, the amount of hematopoietic, or blood, stem cells in the zebrafish increased.
So, extra prostaglandin E2 might be able to help treat someone who's getting a blood
stem cell transplant, like a leukemia patient or someone with a blood or immune system disorder.
Which is great news!
This discovery eventually led to the creation of a drug called ProHema that's supposed
to improve the success of hematopoietic stem cell transplants using blood from umbilical
cords.
Between 2014 and 2015, it went through stage II clinical trials where it was tested on
patients to see how well it works.
And the results are pretty promising.
In patients who were taking ProHema, stem cell transplants seemed to start working earlier
than the control group.
So, ProHema might help improve the effectiveness of these stem cell transplants, but it still
needs to be tested more.
A specific trait of zebrafish might also help scientists with regenerating human tissue.
If a zebrafish heart gets damaged, it can regenerate.
Even if part of the heart is removed, it'll just form a clot at the wound site, which
eventually gets replaced with new cardiac muscle.
But if part of a human heart gets damaged -- like from a heart attack -- the damaged
area generally just turns into scar tissue, which doesn't pump as well as healthy tissue.
If you could regenerate healthy cardiac muscle instead, you could avoid that permanent damage.
While it's still being studied, it seems like the reason zebrafish can do this and
we can't is because the injury activates their cardiac muscle cells, which then regrow
the tissue.
As scientists learn exactly how that's done, the idea of human tissue regeneration might
get closer to becoming a reality.
So the zebrafish may be tiny.
But it's helping modern medicine in a big way.
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