CAMBRIDGE, Mass. — In 1993, Leonard Zon had 110 fish tanks and an idea.
Zon, a professor of stem cell and regenerative biology at Harvard University, thought to study human diseases in zebrafish. The freshwater fish, native to the streams and rice paddies of India and Myanmar, struck him as an ideal model animal for laboratories: Its eggs are transparent, allowing scientists to observe developing organs just by peering into a microscope, and female fish can lay hundreds of eggs a week.
More than two decades later, he now has thousands of tanks housed in two separate facilities — and zebrafish, alongside fruit flies, worms, and mice, are one of the most ubiquitous lab animals worldwide.
This video shows what it’s like inside Zon’s zebrafish room, one of the largest zebrafish facilities in the world.
“Zebrafish is a wonderful system to study disease,” said Zon. “They’re essentially embryo factories. … [This] allows you to study as many genetic diseases as possible and do it very effectively.”
Zon’s lab is focused on studying blood diseases and cancer.
Through these tiny fish, he’s found genes that cause human diseases and developed drugs that have made their way to the clinic.
Zon said he likes to walk through the rows of tanks and observe the fish swimming, sometimes spotting some “interesting tumors” along the way.
“That’s how I space out.”
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Nealy 90% of drugs fail to translate from rodents to humans even though the protein-coding regions of the mouse and human genomes are 85% identical. I wonder why are we wasting our taxpayer dollars on researching human diseases in a fish when its protein-coding regions are only 70% identical to that of humans. Funnily enough we haven’t learn from the recent experience from the TGN 1412 monoclonal antibody saga, reflecting an inadequate prediction of the human response based on primates studies which shares a higher similarity then rodents and the far fetched Zebrafish!!!
Nobody has every used zebrafish a direct preclinical model for human tox, as they are not allowed by regulatory agencies to this end. However, they can provide some interesting data on biological mechanisms (signaling pathways, targets, etc.( very quickly and en masse. As for the mAb TGN 1412, according to your logic, no drug should ever be tested in rodents or primates because many will fail later on. ??? Failure is a normal part of the drug development process — indeed, of any human endeavor — and animal models are to thank for the thousands of drugs on the market that are helping people every day. That does not mean there is no room for improvement but the track record is pretty damn good, compared to sitting around and doing nothing.
In order to understand a problem with a system you need to understand the processes of the system in a normal setting. Mice, zebrafish, Drosophila, etc, allow us to study these in a more timely, efficient, and economical manner than using primates or humans. If we have an idea of e.g. how a cell directionally migrates and the genes/proteins involved in zebrafish, then we can look for related genes/proteins in higher order species and start from a much more advanced base than otherwise would be the case. This eventually allows us to understand the issues that are awry in diseases. Also, gene targeting/manipulation methods are not appropriate, on many levels, in primates, usually. BTW, I have never worked with zebrafish, I have used mainly mice, for both developmental questions concerning the immune system (B and T cell development mostly) and for disease models.