Zebrafish: The future of disease research
- Deandra Limandibhrata
- Mar 13, 2023
- 3 min read
For many of us when we hear think about animal testing during drug and disease research, we first think about mice, rats and rabbits. The use of such model organisms in published scientific research dates back to 1902 by French biologist Lucien Cuénot, who used mice for his experiments. Since then, and with the rise in genetic engineering, model organisms have played a significant role in making drug discovery much more efficient, allowing for studies and the characterisation of disease pathology. Recently, there has been a new development in model organisms from mammals to vertebrates, as scientists explore the use of Drosophila and more substantially, the Danio rerio — the zebrafish.
History in the making: George Streisinger (1927–1984)
Zebrafishes though naturally found in Southern Asia was introduced into the Western world through aquariums in the 19th century, with the tropical fish being one of the most popular to be kept by hobbyists.
The late George Streisinger was the first to research deeper into zebrafishes as a model organism in the 1960s during a peak in interest in using vertebrates instead of mammals as model organisms. His extensive research into the molecular genetics of the zebrafish to understand it as a system gave scientists after him a runway to acknowledge the vast possibilities this small fish brings to the world of drug testing and understanding disease pathology.
The zebrafish genome project was started at the Wellcome Trust Sanger Institute in 2001 and was completed in 2013. Sequencing the zebrafish genome provided evidence of more than 26,000 protein-coding genes, the largest set of any vertebrate sequenced so far. It also showed that around 70 per cent of human genes have at least one similar gene in the zebrafish.
Tiny beauty, big talent
Though this tiny fish is only at most 6cm in length, not only is it 71% similar to the human genome, but it also has similar major organs to humans such as a spinal cord, intestine, pancreas, liver, bile ducts and even an oesophagus, that share the same features with human systems.
Although mice are evolutionary more similar to humans, the zebrafish has many more advantages such as their rapid breeding rate of approximately 10 days, producing 50 to as many as 300 eggs per time, with a typical lifespan of 2–3 years, and even up to 5 years in captivity.
Furthermore, the embryos are both laid and fertilised externally, which not only makes modification of their genetic makeup much more accessible to create transgenic, knock-in or knock-out lines of zebrafish. This also allows for in vitro fertilisation to be carried out if required. On the other hand, if mice were used, the mother would have to be sacrificed for any gene manipulation as the embryos develop inside the mother, making modification of the embryos inaccessible.
The zebrafish is even more astonishing when compared to its vertebrate counterparts such as the Drosophila, as its embryos and larvae are transparent during the initial stages of development, thus making the zebrafish very suitable for developmental studies as well. Zebrafishes also have a unique ability to repair their own heart muscles, which are excellent to study heart disease and potential drug efficacies.
Current Use and Future Prospects
With the zebrafish holding so much potential in research, many researchers have begun using the fish to model certain diseases such as human melanoma, Duchenne muscular dystrophy and were even used to study the toxicity of nanoplastics on cells and whole organisms.
Researchers have also used zebrafishes to test drug efficacies of Amiodarone to combat arrhythmias, anxiolytic drugs such as LSD, nicotine and naloxone for unconventional anxiety pharmacology and using morpholino to knock down the zebrafish lumican gene to control myopia.
There has been much advancement in clinical research since the initial development of zebrafishes, making it a highly sought after emerging model organism. However, what does this mean for the future of research with zebrafishes?
Evolutionary conservation with the onion model of evolution
Phenomena of relational learning and memory
Increased genome editing with CRISPR/Cas system to generate target mutations
Testing zebrafishes’ cognitive characteristics on their memory and association capabilities with new software
Nuclear abnormality assays and micronucleus testing
Geographical variety of studies on the mutagenicity potential of pollutants
Modelling the effects of different classes of pollutants on mutagenesis
Cytogenic techniques to further discover mutagenic agents that can induce the formation of nuclear abnormalities and micronucleus
Further identification of novel oncogenic drivers to treat human cancer
Modelling multigenic changes in cancer in vivo through knock-out editing
Creating models of young fish with bona fide cancer for chemical screening
Modelling the biology of metastasis under the Zebrafish Mutation Project
Exploring epigenetic changes in cancer and its contribution to cancer phenotypes
The zebrafish may just hold the key to the future of medicine and medical research, and many studies are positive on an upcoming paradigm that may just make the zebrafish one of the model organisms to make an enormous contribution to scientific research as a whole.
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