Drug discovery is rapidly evolving, restlessly chasing innovation. Yet, its fundamental pillars have remained solid in the last 50 years: for example, model organisms firmly continue to be represented by rodents, to establish efficacy and safety of new molecules, prior to testing on humans. (1) Mice have so far been the most used animal model, although other small mammals take over at times. In the recent years, cost and ethical concerns have led scientists to look elsewhere. Following the worms and fruit flies’ pattern, a new model has joined in the effort: zebrafish. Yes, the popular aquarium fish, that besides the resemblance of its uniform, pigmented, blue stripes, has nothing to do with zebra.
This fresh water, transparent fish, best known as an aquarium pet, has slowly transformed into a scientific star. (2) If, just like me, you are also wandering how it bounced from a sitting room fishbowl to a lab bench, expect to be surprised. Zebrafish have no obvious similarities to humans, but in reality, 70% of all our genes, and 84% of genes known to be associated with human diseases have a zebrafish counterpart. By placing drugs in the aquarium, scientists can quickly assess toxicity and efficacy, saving time and money, necessities in this age of great pressure. (3)
In terms of cost of maintenance, visualization, space, formulation, and reliability, zebrafish is hindering other models. They reproduce and mature much more quickly and cost a fraction of what mice cost to maintain. Their embryos are transparent, small enough to fit under microscopes, and can absorb molecules through their skin. These tiny fish are also easy to manipulate, so researchers can quickly make genetically precise models. (4) For this, treatments are being developed quickly to treat infectious diseases, Alzheimer’s, cardiovascular diseases, neural disorders, cancers, and rare diseases, to name just a few.
Conquering both academic and industrial world, about 10 compounds screened in “the zebrafish avatars” are in or about to enter the clinic. Meanwhile other studies show the transcendent benefit of this model in oncology, neurology, immunotherapy as well as personalized medicine. Indeed, if correctly labeled, their see-through nature allows to see individual cell types inside the body and favors researchers to monitor blood vessels grow or change shape. Moreover, zebrafish are finding a niche at the patient’s bedside, being used for personalized medicine to pinpoint the best treatment plan for a particular patient. (4)
Although much of the zebrafish work is being done by academics, it is increasingly attracting attention from biotech and pharmaceutical industry. (4) Big pharma companies are capitalizing on zebrafish alongside other traditional animal models, but not only. The model is also exclusively used by modern biotech companies, at times conjugated with the most advanced personalized genetic technology, CRISPR/Cas9. (5)
What is personalized medicine or CRISPR/Cas9? Well, this is a topic for another blog. As for now, I leave you with the idea that model systems in the pharma world are not always usual and predictable, sometimes drugs that save millions of lives can be screened in innovative, unexpected organisms, as the tiny but potent zebrafish.
References:
1. Breyer, M. D., Look, A. T. & Cifra, A. From bench to patient: Model systems in drug discovery. DMM Dis. Model. Mech. ,8 1171–1174 (2015).
2. How the diminutive zebrafish is having a big impact on medical research, https://www.theguardian.com/science/2013/sep/15/zebrafish-human-genes-project. (Assessed on November 11th, 2019)
3. DRUG DISCOVERY - Zebrafish in Preclinical Drug Development - A Small Fish With Big Returns. https://drug-dev.com/drug-discovery-zebrafish-in-preclinical-drug-development-a-small-fish-with-big-returns/. (Assessed on November 10th, 2019)
4. Cully, M. Zebrafish earn their drug discovery stripes. Nat. Rev. Drug Discov.(2019) doi: 10.1038/d41573-019-00165-x.
5. ZeClinics - Biotechnology CRO - Powering Discovery with Zebrafish. http://www.zeclinics.com/. (Assessed on November 10th, 2019)