By 2023, how far has the genomics revolution progressed?

Original title: 70th anniversary of the discovery of the DNA double helix structure and 20th anniversary of the completion of the Human Genome Project

By 2023, how far has the genomics revolution progressed?

April 25, 2023 marks the 70th anniversary of the discovery of the double helix structure of DNA. This discovery by scientists 70 years ago brought biological research into the molecular age. DNA, which carries the genetic information of life, conveys the mysteries of the ever-changing and endless life of the biological world in such a beautiful posture in the nanoscale space.

For the history of life sciences, 2023 is also of special significance. 80 years ago, Nobel Prize winner in Physics Erwin Schrödinger delivered a speech entitled "What is Life?", which attracted a large number of physicists to devote themselves to life sciences. 20 years ago, scientists from six countries, including the United States, Britain, Japan, France, Germany and China, worked together after years of hard work to complete the human genome sequence map, which also "drew" a milestone in the history of life sciences.

80, 70, 20 years have passed. How far has the genomics revolution progressed? What is the position of China's related fields in the world? What is the significance of "decoding life" and what industrial opportunities will it bring? Xinhua Daily Telegraph reporters have dialogues with many authoritative experts and scholars on many hot topics.

“The mysteries of life are more complicated than we thought, but we have found a way.”

Without the development of genetic research and mature gene analysis technology, humans would not have imagined that elephants and moles are one family, whales and hippos are close relatives, rabbits are much more closely related to humans than to mice, and the genetic difference between humans and chimpanzees is only 1.6%.

Life blooms everywhere in the sky, oceans, deserts, and forests of this planet, but human beings’ understanding of its mysteries is still like a child who has just opened his eyes to see the world.

Reporter: What is the significance of the discovery of the DNA double helix structure and the completion of the Human Genome Project?

He Lin (Academician of the Chinese Academy of Sciences): The impact and value of these events on humanity and the scientific community can be said to be epoch-making.

Take the proposal of the double helix structure of DNA 70 years ago as an example. It essentially launched the era of molecular biology and enabled genetic research to go deep into the molecular level to "decode life". Since then, people have clearly understood the composition and transmission pathways of genetic information. In the following 70 years, various disciplines, led by molecular genetics, have sprung up like mushrooms after rain. One by one, the mysteries of life have been clearly explained from a molecular perspective, and DNA recombinant technology has been greatly promoted, opening up research and applications in the field of bioengineering.

Yang Huanming (Academician of the Chinese Academy of Sciences): About 20 years ago, I was really happy when I got the draft of the human genome, because it was a historic progress. It revealed many mysteries of mankind and is the common heritage and common wealth of all mankind.

At the same time, in front of the sketch, I also understand more clearly how superficial our understanding of biology is. We stand on the shoulders of our predecessors and at a new starting point, and see a wider world and more crossroads ahead. The mysteries of life are more complicated than we imagined, but we have found a way.

Yin Ye (CEO of BGI Group): The Human Genome Project, the Manhattan Atomic Bomb Project, and the Apollo Moon Landing Project are collectively known as the three major scientific projects of the 20th century. These three major scientific projects have promoted a paradigm shift in the development of physical and life sciences, from the original small science operation model guided by personal interests and hypotheses to a large science project model guided by big data and platforms.

The success of the Human Genome Project enabled humans to obtain complete information about the structure and sequence of their own genome for the first time, providing a "navigator" for a large number of genetic studies.

"The cost of sequencing a human genome has dropped from more than $3 billion 20 years ago to $100 today."

The Human Genome Project was proposed in 1985 and officially launched in 1990. At the beginning, five developed countries, namely the United States, Britain, France, Germany and Japan, participated in the project. In November 1997, young and middle-aged geneticists including Wang Jian, Yu Jun, Gu Jun, He Fuchu, He Lin, Zeng Yixin, Gu Dongfeng and Yang Huanming, who attended the Young Genetics Workers' Symposium of the Chinese Society of Genetics, gathered in Zhangjiajie, Hunan. During the several-day meeting, they determined their ambition: to strive to get 1% of the sequencing tasks and catch up with the last train of the Human Genome Project.

The three thousand peaks of Zhangjiajie stand tall and the eight hundred beautiful rivers flow as usual, but the dream that was conceived during this period and the subsequent efforts of all parties have made China the only representative of developing countries in this grand plan concerning mankind. Scientists from six countries worked together to complete the feat and built the human genome spirit of "sharing, contributing and sharing", laying the core foundation for the subsequent development of genetic science.

The unique peaks and beautiful waters of Zhangjiajie are a treasure trove of biological genes, and China is one of the countries with the richest biodiversity. Driven by the "1%" project, the sequencing of the genomes of poultry, livestock, crops, fungi, bacteria, viruses, parasites, and other resource organisms is in full swing in China.

Reporter: What secrets are hidden in DNA? How has the research on genomics in China changed to this day?

He Lin: DNA can accurately replicate itself, maintaining genetic continuity between parents and offspring; it can guide protein synthesis, control metabolic processes and trait development; and under certain conditions, it can produce heritable mutations. It is the beginning of decoding life.

Compared with 20 years ago, China's international status in the field of genomics research has been significantly improved, and its ability to compete with its peers in the world has been greatly enhanced. However, this is a field where everyone is catching up, and any "leading" is not absolutely guaranteed. In addition, the gene industry in my country is developing rapidly, and the economic benefits it generates are also considerable.

He Fuchu (Academician of the Chinese Academy of Sciences): The greatest contribution of the Human Genome Project is to promote the "super Moore's Law" growth of nucleic acid sequencing capabilities, which in turn gave rise to a paradigm shift in biomedical research driven by genomics. Today, genomics has entered its "maturity stage."

In other aspects of life-omics, proteomics still has "growing pains" and metabolomics is "in the ascendant". Therefore, although we have entered the genomic era, we still call for the arrival of the multi-omics or life-omics era.

Xu Xun (President of Shenzhen BGI Life Sciences Institute): The cost of sequencing a human genome has dropped from more than 3 billion US dollars 20 years ago to 100 US dollars today, a decrease of 7 orders of magnitude. In terms of time, it has gone from several years to one day. The development of technology has made genome sequencing easier and easier.

Looking at China's development in the field of genomics over the past 20 years from a global perspective, it can be said that China has gone from participation to synchronization. In some areas, my country has achieved independent control, such as sequencers, and my country's sequencers are world-leading in terms of throughput, accuracy, and cost-effectiveness, and have been recognized worldwide. However, single-molecule long-fragment sequencers and other technologies still need to catch up.

At the same time, we should also note that at present, my country still relies on imports for high-end mass spectrometry for proteome detection, cryo-electron microscopy for protein structure analysis, and most key test kits for life sciences. We urgently need to further lay a solid foundation for life sciences, promote the further independent control of high-end scientific research equipment and source core tools, promote the continuous iteration of domestic equipment, and continuously conquer key core technologies.

Three major trends in the genomics industry

The industry has reached a consensus that the genomics industry has three major trends: precision medicine, future agriculture, and biomanufacturing.

With current medical technology, we can detect more than 7,000 genetic diseases, but we can diagnose less than 300 of them. There is still a huge room for development in precision medicine. By improving the genes of microorganisms in the soil, rice can be grown in the desert. Biomanufacturing has broad application prospects in medicine, drugs, agriculture, materials, environment and energy.

Reporter: What changes have the implementation of a series of genomics projects and the development of proteomes, transcriptomes, etc. brought to various fields such as medicine, agriculture, and energy?

He Fuchu: The success of the Human Genome Project and subsequent genome research gave rise to the concept of "precision medicine" and opened up the clinical practice of personalized medicine. However, it is difficult to truly popularize "precision medicine" based on genomics alone. To address this problem, Chinese scientists have taken a different approach and developed proteomics-driven precision medicine.

For example, my laboratory can further divide tumors of the same pathological type into three molecular subtypes through big data analysis of the proteome of hepatocellular carcinoma patient samples. The classification of subtypes is closely related to prognosis. Subsequent translational research is currently being carried out in the hope that more hepatocellular carcinoma patients will benefit.

Xu Xun: Precision medicine is essentially the use of multi-omics technology with genome as the core to analyze, identify, verify and apply biomarkers of large sample populations and diseases, so as to accurately find the cause of the disease and the target of treatment, achieve personalized precision treatment, and improve the effectiveness of disease diagnosis, treatment and prevention.

In future agriculture, customized precision breeding through genome sequencing can adapt to the needs of different planting environments and different agricultural products.

In terms of biomanufacturing, through genome reading and writing technologies such as synthetic biology, the production and manufacturing of materials, key drug ingredients, energy, etc. can be achieved through methods such as biological fermentation.

Wu Liwen (Doctor and Head of the Department of Neurology at Hunan Children's Hospital): As a clinician, I feel that genomics is developing very rapidly. Many difficult diseases that can be diagnosed now could not be diagnosed or were even misdiagnosed a dozen years ago.

I treated an 8-year-old girl who had delayed motor development and was weak in walking, running and climbing stairs. Later, she had to be carried on someone's back to go to school. Her condition was better in the morning or in the afternoon, and it was fluctuating. We considered that she had congenital myasthenia syndrome rather than myasthenia gravis, so we did a targeted genetic test for her. The result showed that it was fluctuating myasthenia caused by gene mutation. With the current medical level, there are very good treatment options for this disease. She can now walk, run and jump, and has lived a normal life.

The rapid development of genomics in recent years is also inseparable from the overall progress of instrument machinery and material science. Basic scientific research must be ahead of clinical research, and clinical practice will feed back to technological iteration. As long as there is a breakthrough in precision medicine, it can solve many major problems in families.

Yin Ye: It is estimated that the input-output ratio of the Human Genome Project is huge, with an investment of US$3.8 billion bringing a return of hundreds of billions of dollars. In addition, the rapid development of this technology has brought about the rapid coordinated development of physics, chemistry, mathematics and information technology, and has brought about comprehensive breakthroughs in precision medicine, public health, modern agriculture, energy and environmental protection, and biodiversity.

In medicine, the most iconic application is non-invasive prenatal genetic testing, which can detect abnormalities in the chromosomal structure of the fetus through the peripheral blood of the pregnant woman, thereby avoiding the occurrence of a large number of birth defects including Down syndrome, allowing countless families to say goodbye to "genetic tragedy."

In agriculture, after the draft of the Human Genome Project was completed, the genomes of a large number of important crops began to be deciphered. The most representative one for China is rice. We were the first in the world to complete the framework map and detailed map of the rice genome, which established our position in Asian genomics. In 2018, after active efforts by Chinese scientific research teams, Nature magazine agreed that the names of the two major rice cultivars should not be "japanica" and "indica", but "geng (粳)" and "xian (籼)". (Reporters Wang Ruochen and Zhang Ge)