Skip to content

One Fish, Two Fish, Red Fish, Glow Fish

The image shows a fishbowl against a pink background. There is a zebrafish in the fishbowl. The image is split in half, the left side of the zebrafish appears normal in color, while the right side glows a fluorescent green.

Written by Sydney Steiman
Illustrated by Edlin Liang

When I was younger, I had a lava lamp on my bedside table that I would stare at for hours when I couldn’t fall asleep. While the blue lights and shimmering silver glitter were mesmerizing to my young eyes, I always thought it would be more interesting if my dog glowed instead. Little did I know how possible that would be.

The idea of genetically engineering animals and different species is not novel, the fascination started with the 1962 discovery of green fluorescent protein (GFP) by Osamu Shimomura, Martin Chalfie, and Roger Y. Tsein. The 238 amino acid long barrel-shaped protein was found in the Aequorea Victoria jellyfish, and its profound discovery led to a Nobel Prize in Chemistry in 2008.¹ The protein contains a chromophore, a group of atoms that absorb visible light and emit and reflect a different wavelength of light. For GFP, the chromophore is formed with specific amino acids absorbs ultraviolet and emits green light which can be visualized underneath a microscope.²,³The discovery of a glowing protein in jellyfish led scientists to wonder whether this effect could be demonstrated in other organisms or used as a molecular tag to track molecules and proteins in cells. Initial testing in worms showed that when GFP is present beside a gene undergoing expression, the product and resulting organism will glow green under the ultraviolet or blue light.⁴ Today, GFP and other colourful fluorescent proteins are utilized to study protein interactions, effects of small molecules, and gene expression. Additionally, while GFP was a groundbreaking step in understanding gene expression, the protein has been modified to fluoresce under blue light for visualization without ultraviolet light and be even brighter. For example, enhanced green fluorescent protein (EGFP) is a modified version of GFP that is brighter and more stable at higher temperatures and varying pHs. Furthermore, Green Lantern is another variation of GFP that has been documented to be brighter than EGFP by altering the chromophore and specific amino acids in the protein to increase stability.⁵,⁶ While the research field is propelled forward with GFP and its variants, a company called GloFish decided to take this concept in a different direction. 

The image shows a green fluorescent jellyfish. In the upper right corner an enlarged image of the GFP protein is shown to highlight where GFP was discovered.

Danio rerio, zebrafish, are one of the most utilized model organisms to study because they have transparent embryos, have short development times, share 70% of their genetic code with humans, and are small. Major breakthroughs in therapeutics development for heart disease and cancer have been facilitated with zebrafish models, further exemplifying their power.⁷ In 1999 at the National University of Singapore, Dr. Zhiyuan Gong’s research group was studying pollutants in the water using genetically engineered zebrafish that expressed GFP signal when toxins were present.⁸ These fish were created using transgenesis, the process of adding foreign genes to the genome of an organism. In this case, the gene that encodes GFP is linked to a promoter’s DNA sequence, a sequence required for transcription of your gene of interest and ensures that your GFP protein is being expressed. This engineered DNA is then microinjected into the fish’s embryo where it will be taken up by the cell’s nucleus and incorporated into the genome. Once the zebrafish grow and the GFP signal is apart under blue light, the fish are selectively bred.9 This glowing fish discovery was quickly trademarked and patented by the scientists and a partnered American group from Texas to market the fish for blue light-containing aquariums and the public. GloFish became the first genetically modified pets for purchase in 2003, however where they are sold is restricted.10

These mesmerizing fish can only be sold through GloFish certified providers such as direct from the company and select retailers. However, in 2004, the company underwent a lawsuit filed by the Center for Food Safety in the United States due to the possibility of these fish becoming invasive species through the destruction of natural habitats and the worry of opening the floodgates to the possibility of unethically genetically modifying other organisms. Despite the controversy and wary pet store sellers, GloFish is still widely available in both Canada and the United States, except for California.¹¹,¹² Additionally, while GFP was the ‘founding father’ for these glowing fish, GloFish now sells orange, pink, purple, red, and blue glowing fish.¹³

The interest and methods of creating animals that glow are not restricted to fish, in the past 25 years many labs and companies have tried to genetically engineer cats, dogs, sheep, pigs, and even monkeys to fluoresce green when in the presence of blue light.¹⁴ While it is crucial to understand the ethical ramifications of altering the genetic code of these organisms it is important to recognize how far the research field and genetics have come.

Sources:

  1. Swaminathan, S. GFP: the green revolution. Nature Cell Biology. 2009 Oct 01:11. doi:10.1038/ncb1953
  2. Paul BK, Guchhait N. Looking at the Green Fluorescent Protein (GFP) chromophore from a different perspective: A computational insight. Spectrochimica Acta Part a: Molecular and Biomolecular Spectroscopy. 2013 Feb 15:295-303. doi:10.1016/j.saa.2012.11.007
  3. What is GFP? – Phospho Biomedical Animation 2017
  4. Merritt C, Gall CM, Rasoloson D, Seydoux G. Transgenic solutions for the germline. In: WormBook: The Online Review of C. elegans Biology [Internet]. 2005-2008. Available
  5. Kandel ES, Chang BD, SchottB, Shtil AA, Gudkov AV, Roninson IB. Applications of Green Fluorescent Protein as a Marker of Retroviral Vectors. Somatic cell and molecular genetics. 1999. doi:10.1007/BF02674280
  6. Cell guidance systems. Green fluorescent protein: GFP legend and legacy. 2021 Dec 20. [accessed 2024 Oct 20]. https://www.cellgs.com/blog/green-fluorescent-protein-gfp-legend-and-legacy.html
  7. Segner H. Zebrafish (Danio rerio) as a model organism for investigating endocrine disruption. Comparative Biochemistry and Physiology Part c: Toxicology & Pharmacology. 2009. doi:10.1016/j.cbpc.2008.10.099
  8. NUS’ glowing fish goes places. [accessed 2024 Oct 20] https://news.nus.edu.sg/nus-glowing-fish-goes-places/
  9. Lin S. Transgenic zebrafish, Developmental Biology Protocols: Volume II. Methods in Molecular Biology. 2000. doi:10.1385/1-59259-065-9:375
  10. Cahalan R. Fishy Business. The Alcalade: The official publication of the Texes exes. 2013. [accessed 2024 Oct 20] https://alcalde.texasexes.org/2013/01/fishy-business/
  11. Curry C. Genetically modified neon ‘GloFish’ could threaten natural species: report. ABCNews. 2012. [accessed 2024 Oct 20] https://abcnews.go.com/blogs/technology/2012/09/neon-genetically-modified-glofish-could-threaten-natural-species
  12. Starr B. Lighten up, California: why GloFish can’t glow in the Golden State. KQED NPR PBS. 2013 Feb 11. [accessed on 2024 Oct 20] https://www.kqed.org/quest/49318/lighten-up-california-why-glofish-cant-glow-in-the-golden-state
  13. [accessed 2024 Oct 20] https://www.glofish.com/glofish.aspx
  14. Hensen L. 7 genetically modified animals that glow in the dark. The Week. [accessed 2024 Oct 20] https://theweek.com/articles/464980/7-genetically-modified-animals-that-glow-dark