A female scientist who loves to "find faults", she has made "eating fish without spitting out the bones" no longer a dream!

Foodies, are you ready for a new era of food without fish bones?

Fish is a popular delicacy in China, but the presence of fish bones often makes people feel nervous while enjoying the delicious food.

Can I eat a fish without bones? This dream of foodies used to be a fantasy, a pipe dream, but now, this dream is expected to become a reality.

Gao Zexia

In 2024, Professor Gao Zexia and her team from Huazhong Agricultural University brought good news: after years of scientific research, they have bred grass carp without spines. Before that, they had already bred zebrafish and Wuchang fish without spines. These achievements were made possible by Gao Zexia's "nitpicking" character.

Planting the dream of using gene editing technology to "find faults"

Gao Zexia entered Huazhong Agricultural University to study aquaculture in September 2001. After successfully transferring to a doctoral program in her second year of graduate studies in 2007, she became the first international joint doctoral student in her college and went to Ohio State University in the United States for exchange studies. She returned to the university in 2010 after completing her studies.

At the beginning, Gao Zexia's team mainly studied Wuchang fish. With her solid foundation and strong research ability, the inquisitive girl successfully overcame related problems. But she found that after these problems were solved, the price of Wuchang fish still could not be raised. Why? After some research, she found the key point - Wuchang fish has many bones and is not easy to sell!

Can I use what I have learned to solve the problem of too many fish bones in Wuchang? Curious, Gao Zexia began to look up relevant literature and found that some scholars had paid attention to this issue before, but they had not conducted in-depth research. This is an area that few people have touched upon, which is enough to show how difficult it is, but Gao Zexia, who dares to think and fight, decided to give it a try. After some research, she decided to focus on the bones between fish.

During the evolution of fish, the intermuscular spines of some fish have gone through a process of softening and degeneration. The perch of the order Perciformes and the yellow catfish of the order Siluriformes do not even have intermuscular spines. However, because the breeding cost of fish without spines is generally high, or they are "delicate and difficult to raise", the main fish species chosen by Chinese people are mainly species with a certain number of intermuscular spines, such as silver carp, grass carp, bighead carp, carp, crucian carp, and bream. If the problem of intermuscular spines of these fish can be overcome, it will undoubtedly be a good thing for the country and the people.

"Theoretically, if we can find the master gene for the formation of intermuscular spurs, we can use gene editing technology to prevent Wuchang fish from growing intermuscular spurs." Careful consideration gave Gao Zexia the courage to move forward. "In addition, our parents, elders and myself all have lumbar disc herniation problems, and the study of intermuscular spurs is also somewhat related to bone hyperplasia (commonly known as bone spurs). "With dreams comes motivation, and Gao Zexia embarked on this journey of "picking out faults" using modern gene editing technology.

It's not easy to be a detective

On the road of scientific research, ideals are always beautiful, but reality is often full of challenges.

In the process of exploring the intermuscular spines of Wuchang fish, Gao Zexia and her team encountered a seemingly impossible task - to pick out 84 to 146 intermuscular spines (the average number, with individual differences) from each sexually mature Wuchang fish and extract high-quality transcriptome RNA from them to study the relationship between the formation of intermuscular spines and gene expression.

Shaving the connective tissue of the bream bones and fish bones

This work is technically very difficult. First, it is necessary to accurately locate the position of each intermuscular thorn, and then carefully pull out these small thorns that are adhered to the connective tissue under anesthesia. Next, she and her team must quickly remove the attached muscle tissue and freeze it before the RNA degrades to ensure that high-quality RNA samples can be extracted.

After three months of unremitting efforts, Gao Zexia and her students finally mastered this "fish bone picking" technology and successfully applied for the world's first national patent on fish bone research. This technology not only improves the efficiency of RNA extraction, but also lays the foundation for subsequent gene expression research.

After an in-depth analysis of the differences in gene and protein expression between the intermuscular spines of Wuchang fish and other skeletal tissues, Gao Zexia's team gradually revealed the key genes that affect the growth and development of intermuscular spines. They screened out 3 genes from more than 60 candidate genes that regulate the occurrence of fish intermuscular spines to varying degrees. Like a patient detective, they continued to collect evidence, piece together clues, and proceed steadily step by step. In the end, they found the truth-the loss of the runx2b gene can cause the complete loss of intermuscular spines! "There really is no intermuscular spine! We couldn't believe it at the time." After the mystery was solved, Gao Zexia couldn't calm down for a long time.

In 2019, Gao Zexia's team discovered the key role of the runx2b gene in the intermuscular spines of fish. They first verified this discovery in zebrafish, and then began to explore the application of this technology to Wuchang fish and other economic fish in 2020. By 2021, they successfully implemented gene editing in Wuchang fish, and obtained Wuchang fish without intermuscular spines in 2022. In the same year, the team also applied this technology to grass carp, a fish that matures later. After two years of hard work, Professor Gao Zexia's team not only cultivated spineless F1 generation grass carp seedlings, but also screened out more than 500 grass carp individuals without small spines. These individuals were used to breed the F2 generation, and the results showed that all offspring were spineless grass carp, and this trait could be inherited. The successful breeding of spineless grass carp provides consumers with a new choice, making this widely farmed fish likely to bring a more convenient eating experience in the future.

Strive to bring "fish without small bones" into thousands of households

Is boneless fish safe? What does it taste like?

Students from the College of Fisheries of Huazhong Agricultural University shared their experience of tasting Wuchang fish without intramuscular bones: "It is more tender than normal grass carp," "It tastes similar to sea bass, with garlic meat," "The texture, taste and flavor are the same as ordinary Wuchang fish. The only difference is that there are no intramuscular bones. It is really delicious. You don't have to worry about bones when you take a big bite."

Comparison chart

After testing, the protein, trace elements, and amino acid content of the "boneless" grass carp are similar to those of ordinary grass carp. Compared with other freshwater fish, grass carp can also use lower feed costs in exchange for more high-quality protein, and their excrement components are also more friendly to the water quality environment.

At present, Gao Zexia's team has made phased progress in the research of "freshwater fish without intermuscular spines", and the team is also seeking further cooperation to explore the possibility of silver carp without intermuscular spines. In the future, this technology is expected to be extended to major freshwater fish species such as silver carp and bighead carp. The team is also committed to transforming the breeding model of boneless fish from traditional ponds to modern factory breeding, and conducting a more in-depth assessment of the nutritional quality of these fish. They firmly believe that with the implementation of relevant national policies on gene editing breeding in the future, "fish without small spines" will surely enter thousands of households.