Every reporter: Ke Yang Every editor: Zhang Haini
Increasing agricultural income, sterilizing mosquitoes, and transplanting pig heart organs...... Together, these seemingly disparate scenarios point to a highly disruptive and controversial technology: gene editing.
Wei Wensheng, director of the Genome Editing Research Center at Peking University, likened gene editing technology to the code of life science, "In fact, all our living cells are encoded, and its lowest genetic information is actually composed of four letters, which is ATCG." What are we making up? It's its permutations. ”
ATCG – Adenine (A), Thymine (T), Cytosine (C), Guanine (G), the genetic information of all life on Earth is stored in four key chemicals.
Search, Position, Cut, Knockout, Copy, Write, Overwrite, ...... It sounds like a tool used to operate a computer, but it also exists in gene editing. Gao Caixia, director of the Center for Genome Editing at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, explained that gene editing involves two main modules: the first module is like our GPS or search function, which can quickly locate a specific gene locus in a long gene sequence. Once the positioning is accurate, a second module, the Edit Module, is launched to make precise modifications. This process is similar to using an eraser to make modifications and then using a pencil to write.
How does gene editing subvert agriculture and save lives? How to guide it to good? At the recording site of the "Dialogue" column of CCTV's financial channel, the reporter of "Daily Economic News" noticed that Gao Caixia, director of the genome editing center of the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, and director of the genome editing research center of Peking University. Wei Wensheng, the leading scientist of Changping Laboratory, Cai Daqing, the founding managing partner of Sherpa Investment, Zhang Hui, the general manager of Shandong Shunfeng Bioscience and Technology Co., Ltd., Zheng Biao, the CEO of Shanghai BRL Biotechnology Co., Ltd., and Mao Changqing, vice president of the Crop Science Society of China and president of Xiangtian Technology Co., Ltd., gathered together to find a consensus on the future development of gene editing from the dining table to life and health.
Image source: Courtesy of CCTV's "Dialogue" column
Before subverting the logic of agricultural production, when will gene-edited food be on the table?
On April 28, the Ministry of Agriculture and Rural Affairs issued the "2023 Approved List of Biosafety Certificates for Agricultural Gene Editing (Production and Application)". This is the country's first plant gene editing safety certificate, which contains many crops that are often on the table. This is a landmark event of mainland gene editing in the field of agriculture.
At the show, Zhang Hui showed a "high oleic soybean", which is one of the products that obtained the gene editing biosafety certificate in April this year. In appearance, this soybean is no different from ordinary soybeans, but its oleic acid content is significantly higher than that of ordinary soybeans. Through gene editing technology, the oleic acid content of this soybean has been increased from 20% to 80% of ordinary soybeans. Another tomato variety he showed was the "High GABA Tomato". GABA, which stands for γ-aminobutyric acid, is a nutrient that has antihypertensive and anxiety-relieving effects.
The use of gene editing technology can significantly increase the nutrient content of some foods, but does this mean that such substances can be welcomed by consumers?
Previously, Canadian scientists have succeeded in creating a new species called "eco-pig" through gene editing technology, which has reduced the phosphorus content in its feces by 75%, which has played a huge role in protecting the environment. However, consumers were reluctant to let such pork be served on the table, and eventually, the world's last eco-friendly pig was euthanized.
In the face of the products of new technologies, people often have more worries and doubts than support and recognition. Will domestic consumers be willing to accept such gene-editing products?
Gao Caixia is not worried about this problem, she uses some common foods as examples: "Rape has a natural mutant, it is high oleic acid rape, in fact, the principle is the same as this (gene editing technology), the same gene is knocked out, (but rapeseed) is a naturally obtained mutant, this (gene editing) is artificially obtained." The movements are exactly the same, and the quality (is) not changing. ”
Gao Caixia Image source: Courtesy of CCTV's "Dialogue" column
In the future, gene editing will subvert, or subvert, the traditional logic of human agricultural production. This disruptive prospect has sparked a possible imagination that in the future humans may expand into more edible species.
Lupin, which is usually called Lu Binghua, Gao Caixia used it as an example. Lupins are extremely high in protein and dietary fiber, but they contain harmful alkaloids. Through gene editing technology, the genes related to the alkaloid synthesis pathway can be modified to remove harmful alkaloid components. In this way, lupins can be turned into a source of high-quality protein. Given the high demand for protein in the mainland, the application of lupine can also be a supplement to protein.
Will these genetically edited foods have side effects on the body after they enter the human body?
Wei Wensheng believes that it is normal for the public to have concerns or doubts about the safety of any new product. But he wanted to emphasize that the biggest concern was about concepts and terms. "For example, people think that as long as it's natural, it's good. Snake venom is natural, but it can poison people, right? For example, after our new products and new crops come out, they still need to go through safety assessments. ”
Gao Caixia pointed out that the Ministry of Agriculture and Rural Affairs has a very standardized regulatory system for gene-edited products, and all aspects such as growing conditions, field release, and nutrients have been strictly monitored. A safety certificate will only be issued after confirmation by the state or the Ministry of Agriculture and Rural Affairs that there is no problem.
Crack the underlying code of the disease
"What we often call 'unsolved medical problems' is (some are) problems with the underlying password, and if you don't change it from the password level, you can't solve the problem. Wei Wensheng mentioned in the show.
In the wide range of application scenarios of gene editing technology, in addition to the plant field, another concern is undoubtedly medical treatment.
Zheng Biao introduced that gene editing, as an emerging biomedical method, has a very prominent revolutionary breakthrough. The advent of this technology has made it possible to cure diseases that doctors were unable to do.
In China, there are 300,000 patients with moderate to severe thalassemia, and 30 million are gene carriers.
Zheng Biao revealed that in the past, the traditional treatment for thalassemia was blood transfusion. In general, transfusion-dependent patients with thalassemia major require blood transfusions approximately every 4 weeks. A patient weighing 40 kg needs 8,000 ml of blood a year, but even if the patient receives a standardized blood transfusion, only half of the patients will survive past the age of 35.
How can this disease be cured?" Zheng Biao introduced that thalassemia is because of the mutation of genes, which makes the patient have problems producing normal hemoglobin, so the red blood cells produced are very few, and they return to normal after modification.
Currently, the study is in phase 1 clinical trials.
Just as it is possible for a careless programmer to type the wrong code and cause downtime, is it possible for the gene editing technology that writes the code of life to make a mistake and accidentally type the wrong genetic code?
Gao Caixia said: "Isn't it enough to do gene editing, there are so many tools in the toolbox? ”
Zheng Biao mentioned that the big problem of gene editing is off-target. "Nothing can be perfect. We must now exhaust all our means, and we must not let perfection stifle superiority. ”
Wei Wensheng's view is that any technology has risks, and gene editing will also face various risks. The upper limit of researchers is actually basic research, "it (basic research) is our 'ceiling', which (determines) how deep and in place our understanding of disease mechanisms is."
With the emergence and iteration of some new technologies, scientists' "ultimate pursuit" of gene editing technology will also receive more assistance.
For example, artificial intelligence.
Gao Caixia used Progeria as an example, and only need to change the T letter in the gene to the C letter to successfully treat the disease. Since the development of this technology in 2016, no more than 10 deaminases have been used by scientists worldwide. However, with the help of artificial intelligence and AlphaFold (note: technology based on artificial intelligence to predict protein structure) to accurately predict proteins, scientists quickly discovered 5 new families with a total of 58 new functional deaminases.
As gene editing technology continues to advance and improve, can it bring hope to overcome thorny diseases such as cancer?
Wei Wensheng believes that gene editing has a very broad application prospect in the treatment of cancer, but he also stressed that gene editing should not be considered or expected to dominate the world.
Wei Wensheng further said that the pathogenesis of tumors or cancers as a typical case presents a high degree of complexity, and there are significant differences between various cancers and tumors, and the treatment methods are different. For now, gene editing technology is more about complementing and accelerating the innovation of existing treatment modalities. For example, to facilitate the discovery of new drug targets. Based on CRISPR technology, high-throughput functional genomics research is carried out to establish causal relationships by mutating genes, and then quickly identify the cause of the disease. "When you know what's wrong and when it comes time to solve the problem, gene editing may be your choice. But it may not be your choice – a small molecule compound or a drug with this large molecule antibody, or even a cellular therapy can be (as an option). ”
Wei Wensheng Image source: Courtesy of CCTV's "Dialogue" column
Standing on the wind again: the wind rises at the end of Qingping
The research progress in the field of scientific research is in full swing, what kind of challenges are still facing in the implementation of the industry?
In the field of agriculture, Mao Changqing said frankly that from a business point of view, at present, there are many technologies whose business models may not be mature, especially in the face of new products of gene editing, social cognitive changes also need a process, so this market may not be fully mature.
Gao Caixia added that until the real disruption of the agricultural sector is realized, basic research is actually the more difficult part. Gene editing may be a disruptive technology, but the extent to which it can be disruptive depends on breakthroughs in basic scientific research. "Because you have to know which gene to change first, if scientists or scientists doing basic research don't do a good job of studying this piece, I don't think it can be subverted. ”
And in the medical field, in fact, gene editing therapies are nothing new.
As early as the end of the last century, gene therapy to treat genetic diseases by modifying patients' genes has become a "trend". In 1990, the world's first gene therapy was successful, and a 4-year-old girl with an immunodeficiency disease improved significantly after treatment, starting a decade-long search for gene therapy. In 1999, a patient suffered an adverse reaction to treatment and eventually died of liver failure, bringing research into gene therapy to a low point. People are beginning to rethink and rethink the safety and effectiveness of gene therapy.
In November 2023, the world's first CRISPR gene editing therapy was approved for marketing in the UK, marking a milestone in the application of gene editing industry. Now, gene editing therapies are starting to make their way back into the spotlight.
How long will the tuyere last this time?
Wei Wensheng felt that the wind would pass, but the wind would basically not stop. Earlier technologies, especially in the field of biotechnology, such as recombinant DNA, are still being used more and more widely.
Cai Daqing said that when any biotechnology first appears, it will show strong vitality, just as CRISPR gene editing technology has attracted widespread attention. Subsequently, the influx of a large number of talents and capital will lead to a certain bubble in this field, similar to the development process of the Internet industry. But looking back, it's still gratifying to see the social progress that the Internet has promoted.
In the field of biopharmaceutical technology, Cai Daqing believes that monoclonal technology won the Nobel Prize in 1984, and then developed into a huge industry with a scale of more than one trillion yuan, and the industry has also experienced ups and downs. Gene editing technology has gone through three stages: reading, revising, and writing: reading, which refers to gene sequencing, has given birth to a huge industry; renovation, which refers to gene editing and gene therapy, is in the ascendant; and gene synthesis technologies such as synthetic biology are the representatives of this stage of "writing", which also has huge prospects for industrial development. Take CRISPR technology as an example, it is in the early stages of its rise, indicating that the future is full of vitality and vitality.
"Now I think that a technology like CRISPR, it is just 'the wind rises at the end of the green ping', and it is very vital to move forward. Cai Daqing finally said.
The Risks of Evil?Controversy About Gene Editing Technology
Science fiction writers tend to have a richer imagination. Genes can be edited or created, and in a science fiction story, someone has developed a precision weapon for a specific genetic population that is enough to wipe it out, is this a potential hidden danger?
Wei Wensheng said that this has actually been realized in terms of experiments. Gene drive technology is able to transform small populations in a short period of time. For example, changing the gender composition of mosquito populations. He believes that this technology or tool cannot simply be stigmatized, and that all evil deeds actually come from the people who use it. Therefore, people should not only discuss in the technical field, but also need to regulate and regulate human behavior from the perspective of society, law and government supervision.
With the development of gene editing technology, people have also begun to worry about whether gene editing technology will lead to the recurrence of "eugenics" in the future.
Gao Caixia does not deny the technical feasibility. "It's not impossible, it's doable. But whether or not we can do that now, I think there is a specification for this. ”
Wei Wensheng emphasized that there are limitations to people's cognition of any one gene or trait. Among the 3 billion base pairs in the human body, the functions of a large number of sequences are still being studied and explored. The limitations of this perception dictate that the use of technology to perform related operations is bound to be controversial.
Again, in the case of thalassemia, the main cause of the disease is a mutation in the β globin gene, which leads to a decrease in the oxygen capacity of the blood. Why do large numbers of people still carry this defective gene over a long period of evolution?
Wei Wensheng introduced that the Mediterranean region is a high-incidence area of malaria, and malaria parasites are transmitted through hemoglobin. After the mutation of the hemoglobin gene, although the oxygen capacity of the blood is reduced, it also reduces the ability to carry the malaria parasite, which is beneficial to people. This suggests that good and bad can be translatable in some cases. "That's why we need to be cautious about this very serious issue. ”
"There is no good or evil in gene editing. But from the perspective of the pharmaceutical industry, if it is used to treat diseases, it is good. But if you're using it to edit germ cells and create 'superhumans', you're probably going to have to put a big question mark. Zheng Biao thinks.
Gao Caixia said that more importantly, in terms of ethical norms, how the state should regulate. She believes that such technologies should be strictly regulated. Gene editing technology is actually the direct writing and modification of the genome.
Gao Caixia believes that gene editing technology is a fascinating technology. She again cited agriculture as an example, where powdery mildew is a common disease of crops, affecting wheat, barley, tomatoes, strawberries, cucumbers, etc. Sixty years ago, barley breeders successfully developed powdery mildew resistant varieties using traditional breeding methods. After analysis, the cause of the resistance to powdery mildew was that one gene in the mutant was eliminated, and based on this discovery, the same gene of wheat can be knocked out by gene editing technology, and this work can only be done by gene editing technology.
"Why is it that only gene editing can do this work, but God can't do it? Because wheat is a hexaploid and it has three sets of genomes, and this gene is three copies. What is the probability that you want to knock out three copies at the same time? This probability is almost zero. "But through gene editing technology, we can accurately locate and modify genes, knock out three genes at the same time, and quickly breed wheat varieties resistant to powdery mildew.
"Powdery mildew is one of the three major diseases of wheat, and it can be made through gene editing, which is the charm of gene editing. Gao Caixia finally said.
National Business Daily