Genetically modified fish (GM fish) are organisms from the taxonomic clade which includes the classes Agnatha (jawless fish), Chondrichthyes (cartilaginous fish) and Osteichthyes (bony fish) whose genetic material (DNA) has been altered using genetic engineering techniques. In most cases, the aim is to introduce a new trait to the fish which does not occur naturally in the species, i.e. transgenesis.
GM fish are used in scientific research and kept as pets. They are being developed as environmental pollutant sentinels and for use in aquaculture food production. In 2015, the AquAdvantage salmon was approved by the US Food and Drug Administration (FDA) for commercial production, sale and consumption, making it the first genetically modified animal to be approved for human consumption. Some GM fish that have been created have promoters driving an over-production of "all fish" growth hormone. This results in dramatic growth enhancement in several species, including salmonids, carps and tilapias.
Critics have objected to GM fish on several grounds, including ecological concerns, animal welfare concerns and with respect to whether using them as food is safe and whether GM fish are needed to help address the world's food needs.
History and process.
The first transgenic fish were produced in China in 1985. As of 2013, approximately 50 species of fish have been subject to genetic modification. This has resulted in more than 400 fish/trait combinations. Most of the modifications have been conducted on food species, such as Atlantic salmon ("Salmo salar"), tilapia (genus) and common carp ("Cyprinus carpio").
Generally, genetic modification entails manipulation of DNA. The process is known as cisgenesis when a gene is transferred between organisms that could be conventionally bred, or transgenesis when a gene from one species is added to a different species. Gene transfer into the genome of the desired organism, as for fish in this case, requires a vector like a lentivirus or mechanical/physical insertion of the altered genes into the nucleus of the host by means of a micro syringe or a gene gun.
Uses.
Research.
Transgenic fish are used in research covering five broad areas
Most GM fish are used in basic research in genetics and development. Two species of fish, zebrafish ("Danio rerio") and medaka (Japanese rice fish, "Oryzias latipes"), are most commonly modified because they have optically clear chorions (shells), develop rapidly, the 1-cell embryo is easy to see and micro-inject with transgenic DNA, and zebrafish have the capability of regenerating their organ tissues. They are also used in drug discovery. GM zebrafish are being explored for benefits of unlocking human organ tissue diseases and failure mysteries. For instance, zebrafish are used to understand heart tissue repair and regeneration in efforts to study and discover cures for cardiovascular diseases.
Transgenic rainbow trout ("Oncorhynchus mykiss") have been developed to study muscle development. The introduced transgene causes green fluorescence to appear in fast twitch muscle fibres early in development which persist throughout life. It has been suggested the fish might be used as indicators of aquatic pollutants or other factors which influence development.
In intensive fish farming, the fish are kept at high stocking densities. This means they suffer from frequent transmission of contagious diseases, a problem which is being addressed by GM research. Grass carp ("Ctenopharyngodon idella") have been modified with a transgene coding for human lactoferrin, which doubles their survival rate relative to control fish after exposure to "Aeromonas" bacteria and Grass carp hemorrhage virus. Cecropin has been used in channel catfish to enhance their protection against several pathogenic bacteria by 2–4 times.
Recreation.
Pets.
GloFish is a patented technology which allows GM fish (tetra, barb, zebrafish) to express jellyfish and sea coral proteins giving the fish bright red, green or orange fluorescent colors when viewed in ultraviolet light. Although the fish were originally created and patented for scientific research at the National University of Singapore, a Texas company, Yorktown Technologies, obtained the rights to market the fish as pets. They became the first genetically modified animal to become publicly available as a pet when introduced for commercial in 2003. They were quickly banned for sale in California; however, they are now on shelves once again in this state. As of 2013, Glofish are only sold in the US.
Other transgenic lines of pet fish include Medaka which remain transparent throughout their lives and pink body color transgenic angelfish ("Pterophyllum scalare") and lionhead fish expressing the Acropora coral ("Acroporo millepora") red fluorescent protein.
The ocean pout type III antifreeze protein transgene has been successfully micro-injected and expressed in goldfish. The transgenic goldfish showed higher cold tolerance compared with controls.
Food.
One area of intensive research with GM fish has aimed to increase food production by modifying the expression of growth hormone (GH). The relative increases in growth differ between species.(Figure 1) They range from a doubling in weight, to some fish that are almost 100 times heavier than the wild-type at a comparable age. This research area has resulted in dramatic growth enhancement in several species, including salmon, trout and tilapia. Other sources indicate an 11-fold and 30-fold increase in growth of salmon and mud loach, respectively, compared to wild-type fish. Transgenic fish development has reached the stage where several species are ready to be marketed in different countries, for example, GM tilapia in Cuba, GM carp in the People's Republic of China, and GM salmon in the US and Canada. In 2014, it was reported that applications for the approval of transgenic fish as food had been made in Canada, China, Cuba and the United States.
Over-production of GH from the pituitary gland increases growth rate mainly by an increase in food consumption by the fish, but also by a 10 to 15% increase in feed conversion efficiency.
Another approach to increasing meat production in GM fish is "double muscling". This results in a phenotype similar to that of Belgian Blue cattle in rainbow trout. It is achieved by using transgenes expressing follistatin, which inhibits myostatin, and the development of two muscle layers.
AquAdvantage salmon.
In November 2015, the FDA of the USA approved the AquAdvantage salmon created by AquaBounty for commercial production, sale and consumption. It is the first genetically modified animal to be approved for human consumption. The fish is essentially an Atlantic salmon with a single gene complex inserted: a growth hormone regulating gene from a Chinook salmon with a promoter sequence from an ocean pout. This permits the GM salmon to produce GH year round rather than pausing for part of the year as do wild-type Atlantic salmon. The wild-type salmon takes 24 to 30 months to reach market size (4–6 kg) whereas the GM salmon require 18 months for the GM fish to achieve this. AquaBounty argue that their GM salmon can be grown nearer to end-markets with greater efficiency (they require 25% less feed to achieve market weight) than the Atlantic salmon which are currently reared in remote coastal fish farms, thereby making it better for the environment, with recycled waste and lower transport costs.
To prevent the genetically modified fish inadvertently breeding with wild salmon, all the fish raised for food are females, triploid, and 99% are reproductively sterile. The fish are raised in a facility in Panama with physical barriers and geographical containment such as river and ocean temperatures too high to support salmon survival to prevent escape. The FDA has determined AquAdvantage would not have a significant effect on the environment in the United States. A fish farm is also being readied in Indiana where the FDA has approved importation of salmon eggs. As of August 2017, GMO salmon is being sold in Canada. Sales in the US began in May 2021.
Detecting aquatic pollution (potential).
Several research groups have been developing GM zebrafish to detect aquatic pollution. The laboratory that developed the GloFish originally intended them to change color in the presence of pollutants, as environmental sentinels. Teams at the University of Cincinnati and Tulane University have been developing GM fish for the same purpose.
Several transgenic methods have been used to introduce target DNA into zebrafish for environmental monitoring, including micro-injection, electroporation, particle gun bombardment, liposome-mediated gene transfer, and sperm-mediated gene transfer. Micro-injection is the most commonly used method to produce transgenic zebrafish as this produces the highest survival rate.
Regulation.
The regulation of genetic engineering concerns the approaches taken by governments to assess and manage the risks associated with the development and release of genetically modified crops. There are differences in the regulation of GMOs between countries, with some of the most marked differences occurring between the US and Europe. Regulation varies in a given country depending on the intended use of the products of the genetic engineering. For example, a fish not intended for food use is generally not reviewed by authorities responsible for food safety.
The US FDA guidelines for evaluating transgenic animals define transgenic constructs as "drugs" regulated under the animal drug provisions of the Federal Food and Cosmetic Act. This classification is important for several reasons, including that it places all GM food animal permits under the jurisdiction of the FDA's Center for Veterinary Medicine (CVM) and imposes limits on what information the FDA can release to the public, and furthermore, it avoids a more open food safety review process.
The US states of Washington and Maine have imposed permanent bans on the production of transgenic fish.
Controversy.
Critics have objected to use of genetic engineering per se on several grounds, including ethical concerns, ecological concerns (especially about gene flow), and economic concerns raised by the fact GM techniques and GM organisms are subject to intellectual property law. GMOs also are involved in controversies over GM food with respect to whether using GM fish as food is safe, whether it would exacerbate or cause fish allergies, whether it should be labeled, and whether GM fish and crops are needed to address the world's food needs. These controversies have led to litigation, international trade disputes, and protests, and to restrictive regulation of commercial products in most countries.
There is much doubt among the public about genetically modified animals in general. It is believed that the acceptance of GM fish by the general public is the lowest of all GM animals used for food and pharmaceuticals.
Ethical concerns.
In transgenic fast-growing fish genetically modified for growth hormone, the mosaic founder fish vary greatly in their growth rate, reflecting the highly variable proportion and distribution of transgenic cells in their bodies. Fish with these high growth rates (and their progeny) sometimes develop a morphological abnormality similar to acromegaly in humans, exhibiting an enlarged head relative to the body and a bulging operculum. This becomes progressively worse as the fish ages. It can interfere with feeding and may ultimately cause death. According to a study commissioned by Compassion in World Farming, the abnormalities are probably a direct consequence of growth hormone over-expression and have been reported in GM coho salmon, rainbow trout, common carp, channel catfish and loach, but to a lesser extent in Nile tilapia.
In GM coho salmon ("Oncorhynchus kisutch") there are morphological changes and changed allometry that lead to reduced swimming abilities. They also exhibit abnormal behaviour such as increased levels of activity with respect to feed-intake and swimming. Several other transgenic fish show decreased swimming ability, likely due to body shape and muscle structure.
Genetically modified triploid fish are more susceptible to temperature stress, have a higher incidence of deformities
(e.g. abnormalities in the eye and lower jaw), and are less aggressive than diploids. Other welfare concerns of GM fish include increased stress under oxygen-deprived conditions caused by increased need for oxygen. It has been shown that deaths due to low levels of oxygen (hypoxia) in coho salmon are most pronounced in transgenics. It has been suggested the increased sensitivity to hypoxia is caused by the insertion of the extra set of chromosomes requiring a larger nucleus which thereby causes a larger cell overall and a reduction in the surface area to volume ratio of the cell.
Ecological concerns.
Transgenic fish are usually developed in strains of near-wild origin. These have an excellent capacity for interbreeding with themselves or wild relatives and therefore possess a significant possibility for establishing themselves in nature should they escape biotic or abiotic containment measures.
A wide range of concerns about the consequences of genetically modified fish escaping have been expressed. For polyploids, these include the degree of sterility, interference with spawning, competing with resources without contributing to subsequent generations. For transgenics, the concerns include characteristics of the genotype, the function of the gene, the type of