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Behind-the-scenes stories of the Human Genome Project (3)

Text/Qiyun

Third, the significance of human genome research

In 2006, a 13-year, $3.8 billion project to sequence the human genome involving more than a thousand scientists from six countries was finally completed, a massive project comparable to the Apollo moon landing.

The Human Genome Project has revealed the framework map of the human genome, the value contained in it is far more than the gene itself, there is a huge potential in medicine, agriculture, industry, environment, energy and other fields, triggering a new scientific and technological revolution, and it is possible to fundamentally solve the world's population, food, environment, energy and other major problems affecting human survival and development.

The phenomena of life are so brilliant and colorful, and the mysteries of life are so endless. Studying all the genes in the genome makes it possible to uncover all the mysteries of life. The goal of the Human Genome Project can be likened to establish the periodic table of elements of life, the number of elements is limited, but the composition of matter is infinite; the number of genes is finite, and the phenomenon of life is infinite.

The human genome map established by the Human Genome Project can be understood as "the second anatomical map of the human body". The anatomical diagram of the human body tells us the composition of the human body, the location, structure and function of the main organs, and the understanding of the characteristics of all tissues and cells to have today's modern medicine. The second human anatomy map drawn by the Human Genome Project will become a reference for disease prediction, prevention, diagnosis, treatment and individual medicine, and will lay the foundation for the life sciences, basic medicine and biological industries in the 21st century.

The implementation of the Human Genome Project will also promote the development of pharmaceutical, agricultural, industrial and other related industries, resulting in extremely huge economic benefits and immeasurable social benefits.

For example, it can accurately assist drug development.

Before about the 1980s, most drug discoveries originated by chance. Drug molecules and their molecular targets are often unknown. Prior to 2001, the probability of knowing all of a drug's protein targets was less than 50 percent. After the Advent of the Human Genome Project, everything took a turn for the better. In recent years, almost all licensed drugs in the United States have had a clear knowledge of their protein targets. The study also found that of the approximately 20,000 protein sequences offered by the Human Genome Project that could serve as potential drug targets, only about 10 percent, or 2,149 approved drug targets, suggesting that the remaining 90 percent of the proteome is not affected by pharmacology.

The rapid pace of biomedical research is another beneficiary of the Human Genome Project. As the program continues to evolve, biologists who are proficient in the use of research tools, knowledge resources, and the health of the entire human race will be developed. Since the beginning of the Human Genome Project, it has been clear that the acquisition and use of this genetic knowledge is of great significance to individuals and society.

DNA exists in all the cells of all living things on this earth, and man is the most advanced, the most complex, the most important creature, and if you make the human genome clear, it will be much easier to make other organisms. The strategies, ideas, and technologies established by the Human Genome Project in the study of humans constitute a new discipline or genomics in the life sciences that can be used to study microorganisms, plants, and other animals. It can support and advance a range of important fundamental research in the life sciences. Such as the deciphering of genomic genetic language, the structure and functional relationship of genes, the origin and evolution of life, the molecular mechanism of cell development, production and differentiation, and the mechanism of disease occurrence.

The implementation of the Human Genome Project will also promote the combination of life sciences and information science, materials science and high-tech industries; stimulate the development of related disciplines and technology fields; and will drive a number of emerging high-tech industries. Its research results can be directly guided and translated into practical applications, with immeasurable social and economic benefits. Therefore, it can be said that the scientific value and impact of the Human Genome Project on the development of human society will far exceed the Manhattan Atomic Bomb Program and the Apollo Moon Landing Program.

In the medical field, huge breakthroughs and innovations are already foreseeable. Based on the breakthrough of core technologies such as genetic engineering, cell engineering, and biochips, the wide application of emerging biotechnology in the field of medicine has not only greatly transformed the traditional pharmaceutical industry, but also made medical technology move from terminal disease treatment to front-end genetic diagnosis and prevention, opening the door to personalized medicine and precision medicine in the future.

Undoubtedly, researchers have deciphered the human genetic code and specifically studied the genes that cause genetic characteristics such as breast cancer, diabetes, obesity, and asthma, and proposed specific solutions, which are of great benefit to human survival and human eugenics and eugenics.

The human genome project is widely believed by the academic community to be the beginning of an in-depth study of protein-coding genes. The Human Genome Project sketches published in 2001 marked the end of decades of exploration.

From the inception of the Human Genome Project in 1990 to its completion in 2003 (after the 2001 sketch was published), the number of discoveries (or "annotations") of human genes increased dramatically. In the mid-2000s, that number suddenly stabilized — about 20,000 protein-coding genes were discovered, far below the massive estimate of 100,000 that many scientists had previously proposed. While the number of discoveries of protein-coding genes entered the plateau period, interest in the function of individual genes grew rapidly after the human genome project began. Since 2001, 10,000 to 20,000 papers on protein-coding genes have been published every year.

However, the scientific community's interest is focused on a few genes. Before 1990, HBA1 was the most studied—it was a protein that encodes adult hemoglobin. Since 1990, since the CD4 protein is involved in T cell immunity and acts as a cell receptor for HIV, attention has shifted to CD4 (conclusions based on the cumulative number of published literature). However, after the 2001 Human Genome Project sequence sketch, interest in these two genes dwarfed the level of attention paid to other genes. Some of the "star" genes — such as TP53, TNF, and EGFR — are the subject of hundreds of papers each year, while most other genes receive little attention. Statistics found that in 2017, 1% of genes covered 22% of gene-related publication topics.

Of course, in-depth study of genes of profound biological significance is necessary. TP53 is a good example of this — it's critical to cell growth and death, and once it's inactivated or mutated, it causes cancer: between 1976 and 2017, 9,232 academic papers suggested that mutations in the gene were found in more than 50 percent of tumor sequences. Our intuition might be that the more we learn about the same gene, the more motivated we are to explore the rest of the genome.

There was a big debate before the Human Genome Project began: Is it worth mapping the vast non-coding regions of the genome called junk DNA, or genomic dark matter? Thanks in large part to the Human Genome Project, it is now recognized that most functional sequences in the human genome do not code for proteins.

Instead, it is elements such as long-chain noncoding RNAs, promoters, enhancers, and countless gene regulatory sequences that work together to make the genome complex but orderly guide life activity. Variation in these regions does not alter proteins, but affects the progression of life activities by disrupting the networks that control protein expression.

After the human genome project sketch was released, the discovery of non-protein coding elements mushroomed. So far, this increase has exceeded five times the amount of protein-coding gene discovery, and there are still no signs of slowing down. At the same time, the number of publications on these regulatory elements grew during the period covered by the dataset used in this study (1900 to 2017) — for example, thousands of papers on noncoding RNAs that regulate gene expression.

The mapping of the human genome has become an important milestone in the history of human exploration of its own mysteries, and is considered by many analysts to be a sign of the birth of the biotechnology century. However, who would have thought that just over a decade later, with the development and maturity of technology, the cost of completing whole genome sequencing has gradually decreased from $3 billion that year to hundreds of thousands of dollars, thousands of dollars or even less. There are also many consumer-grade genetic testing products for the general public.

Genetic testing of individuals can lead to predictions of multiple diseases and provide deeper insights into individual behavioral characteristics. In addition to the well-known applications of non-invasive prenatal genetic testing and newborn genetic disease screening, individual genetic testing can also target individual lesion genes to achieve early prevention and treatment.

The Human Genome Project requires the cooperation of mathematics, physics, chemistry and other disciplines, which has led to the development of related disciplines. In the development of new technologies, it is necessary to develop high yields, automated DNA sequencing new technologies and data analysis technologies, genome databases and analysis software, gene chip technology, etc., all of which provide great development opportunities.

(The 3rd issue of the series ends here!) To be continued, the next issue is more exciting! Stay tuned! ）

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