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When Kisenosato Yutaka became the first Japanese-born sumo wrestler in two decades to win a grand champion title, he proudly posed for photographers at a press conference. Like any victorious athlete displaying a trophy, the ruddy cheeked, 178-kilogram wrestler took a moment to hoist aloft a prized symbol of his hard-won status—a huge reddish-hued fish.
In Japan, the red seabream has a celebrity status. Its importance stems in part from its name, madai, which sounds similar to the Japanese term omedetai, meaning “congratulatory” or “auspicious,” says Merry White, an anthropologist at Boston University who studies Japanese food and culture. The fish’s particular hue is also associated with luck in Japanese and other Asian cultures. That helps explain why the fish continues to appear in the grip of triumphant sumo wrestlers and the occasional Japanese politician.
Recently, that prized fish has benefited from a bodybuilding boost befitting its sumo association. In 2018, Japanese scientists published research showing how genome editing technology can create a more muscular variety of red seabream. The development is one of the latest examples of how genome editing is transforming the aquaculture industry.
“In my house, we eat this fish on New Year’s Day every year,” says Masato Kinoshita, an assistant professor of applied biosciences at Kyoto University in Japan and a leader of the red seabream project. “We hope our fish will be popular for many people for daily meals,” he adds.
Kinoshita heads the Kyoto University lab that collaborated on the project with researchers from Kindai University in Osaka. Together they modified the red seabream’s genome to make a meatier fish, one with up to 16 percent more flesh. The project only took two years—far faster than what could have been achieved with traditional breeding.
Raising fish with more meat on their bones could boost commercial farming operations for red seabream, which struggle with narrow profit margins because of the high costs of supplying feed and restocking waters with young fish. In Japan, red seabream alone accounts for about 10 percent of the country’s aquaculture industry.
More broadly, genome editing offers many possibilities for boosting the efficiency of fish farming operations—valued at more than US $176-billion in 2017—that currently supply more than half the fish eaten worldwide.
Yet the commercial success of Kinoshita’s supersized seabream, or any other genetically altered fish, hinges on public acceptance. If a modified fish fails to please people’s taste buds, any business plans will be dead in the water. But the red seabream, with its exalted place in Japanese culture, could prove to be a benchmark case: if Japanese consumers will accept this modified fish, more gene-edited seafood may find its way onto dinner plates.
Kinoshita’s red seabream experiment is part of a wave of studies using a popular genome editing tool known as CRISPR-Cas9 to selectively modify the genes of animals by snipping out or adding in new segments of DNA.
The original discovery of CRISPR stems from the work of Japanese researchers conducted at Osaka University more than 30 years ago. In 1987, that team found a curious cluster of repeating genetic sequences while investigating the genome of Escherichia coli bacteria. At the time, they could not figure out the significance of the patterning. Other researchers eventually found the same repeating sequences in many other microbial species.
Years later, in 2002, Dutch scientists dubbed the repeating sequence of genes CRISPR. They also identified nearby cas genes (an acronym for “CRISPR-associated”), which are responsible for producing the Cas9 protein. Cas9 acts like molecular scissors, which bacteria use to snip apart the DNA of invading viruses.
CRISPR’s natural purpose is to store DNA snippets captured from invading viruses, and to help bacteria identify the viruses should they attack again. In the hands of scientists, however, CRISPR and the related Cas9 scissors act together as a natural genome editing tool. Researchers have since harnessed CRISPR-Cas9’s power to snip many organisms’ genomes at specific points, harnessing the cell’s DNA repair mechanisms to surgically add or remove specific sequences of DNA, or even swap out a specific segment in exchange for a custom-made DNA sequence.
If an organism’s genome is successfully modified during its early development, all of the organism’s cells will carry the modified genome. An organism modified in this way can even pass on the changes to its offspring.
Scientists have already used CRISPR-Cas9 to make farmed fish and other marine species more resistant to disease. They’ve also used the technique to make modified fish sterile, minimizing the risk of escapees mingling with their wild brethren. Past Chinese and American studies on yellow catfish, carp, and channel catfish have removed or disabled (“knocking out”) the myostatin gene, which is responsible for regulating muscle development, in an effort to unlock unrestricted muscle growth. (This line of research is, perhaps unsurprisingly, a popular talking point among human bodybuilders.)
Kinoshita and his colleagues followed a similar approach to produce their oversized red seabream, using CRISPR-Cas9 to knock out the myostatin gene in a generation of red seabream. They did this by manipulating fertilized fish eggs that were in the single-cell stage of development. As with many CRISPR-Cas9 experiments, however, the team encountered a common complication: some of their experimental egg cells began to divide before they had fully incorporated the gene editing changes. That led to a first generation of fish born with a mosaic mix of both edited and unedited cells in their bodies.
To overcome that complication, the Japanese team bred their fish together to create a second generation of “pure knockout” fish that only have edited cells. This step ensures Kinoshita and his colleagues can continue breeding the modified red seabream, producing more and more modified fish without the painstaking process of genetically modifying each individual.
“This study adds another solid example that CRISPR-Cas9 is powerful and will likely transform genetic improvement of aquaculture species,” says Ximing Guo, a professor of molluscan genetics and aquaculture at Rutgers University in New Brunswick, New Jersey, who was not involved with the Japanese team’s work. Guo’s team is currently targeting the myostatin gene in molluscan shellfish, such as oysters and clams.
To prevent their edited fish from escaping to the wild, the Japanese team kept their new breed of red seabream in contained tanks on land, and used layered nets to catch any fish or eggs that might flow downstream in water drained from the tanks. They even deployed ultraviolet light irradiation to sterilize their sperm.
There are side effects to the scientists’ genetic tinkering, however. Beyond the added muscle, the new red seabream displays some changes to its bone structure, such as a shorter spine and shorter overall body length. It may also be more sensitive to certain environmental conditions, such as low water temperature, Kinoshita says. The next research steps involve studying those issues and seeing how efficiently the muscular fish converts food into flesh—major factors in determining whether the fish can prove commercially viable.
To reach supermarket shelves, the meatier CRISPR-enhanced fish must first win over two groups: government regulators and the public. But the red seabream’s special status in the Japanese culinary arts and cultural traditions could muddy the waters for public acceptance of a genetically modified version.
The fish prominently features as a dish in Japanese celebrations for the New Year, weddings, and other festivities. Red seabream is also sometimes offered at Shinto shrines, where priests carry out rituals related to ancestor worship and reverence for spirits inhabiting both animate and inanimate objects. Outside of its official duties, one can find red seabream on plates served raw as sashimi, grilled whole, or cooked in rice gruel as part of a tai-meshi.
When anthropologist Merry White and her family lived in Japan, neighborhood kids in Tokyo treated her newborn son to a traditional okuizome ceremony: a meal of rice gruel and red seabream to celebrate his first 100 days of life. Initially, White says her son “twisted up his nose and set his mouth against it,” before a persuasive girl convinced him to try mushing some around in his mouth.
When Japan’s Ministry of the Environment recommended deregulating some genome edited organisms in late 2018, it too faced pushback of a different sort from concerned consumer groups. In Japan, public distaste for genetically modified foods is nothing new: an international survey in 2016 found that Japanese consumers resist the idea of genetically modified foods even more than people in the United States and the United Kingdom.
An international regulatory battle has already taken place over genetically modified organisms that used older genetic engineering techniques to insert genes from other species into organisms. This transgenic class of organisms includes soybean and corn varieties that are widely grown around the world. While much of the world has accepted these modified crops, many countries have discouraged or banned similar efforts to develop genetically engineered animals. One exception is the US Food and Drug Administration’s approval of a fast-growing transgenic salmon developed by AquaBounty Technologies. Sales of that fish in the United States, however, were blocked by Congress in 2016, a ban that was only lifted March 8, 2019.
Unlike the technique that creates transgenic organisms, CRISPR-Cas9 can alter the genome without necessarily introducing foreign genes. Instead, the technique allows the precise editing of genes to induce changes that could otherwise be achieved through traditional breeding, only faster. For instance, traditional breeders have created more muscular varieties of cows, such as the Belgian Blue, and other livestock just by mating animals that had a natural disruption of their myostatin gene. And long before Kinoshita started snipping DNA, aquaculturists created bigger seabream through selective breeding—but that effort took more than 20 years and five generations of fish.
Many researchers using CRISPR-Cas9 to modify fish are conscious of their responsibility to minimize harm. Guo at Rutgers University says it’s important to “be mindful of potential impacts on the environment and human health.” He supports labeling genome-edited fish and shellfish so that consumers can make their own choices.
In March, a Japanese government advisory panel issued a report concluding that gene-edited crop and animal food products would not need special safety evaluations as long as no foreign genes were added. But Japan’s Ministry of Health, Labour and Welfare still needs to officially adopt the recommendations to open the regulatory door for CRISPR-enabled foods in Japan.
That means no members of the public can even get a taste test of the new muscular red seabream just yet. But when the initial research wrapped up in 2017, the Japanese researchers cooked and tasted samples of their fish for the first time. The only difference, they say, was a softer texture.
The Japanese researchers are mindful of the challenges that remain, even if the government does give the regulatory green light—they have already begun preliminary talks with government officials and fisheries that see potential for more productive aquaculture. Kinoshita has also begun his own form of public outreach, holding seminars and attending science cafés to explain how the genome editing technology works. If early reactions are any indication, some of the younger generation may be open to modifying even the oldest culinary traditions.
Correction: A previous version of this article misstated the US policy on transgenic fish and AquaBounty Technologies. While the company’s AquAdvantage salmon eggs and processed salmon were placed on an automatic detention list—essentially blocking importation—in January 2016, the FDA lifted the restriction on March 8, 2019.