1. The accurate map of the human genome will become the leading discipline in the field of life sciences in the 21st century. This has been recognized internationally. Today we stand on the threshold of the new century. Looking back at the beginning of the 20th century, physics It occupies an absolute leadership position in the field of natural science. The prosperity of physics at that time was due to its major breakthroughs in theory, such as Newtonian mechanics, the second law of thermodynamics, quantum mechanics and the subsequent theory of relativity, etc., which gave physics It laid the foundation for the development of physics and the emergence of physics. These theories were unprecedented in the past and were innovative theories for mankind. This is the most fundamental reason why physics became the leading discipline of natural science at the beginning of the 20th century. Since then, physical science has been ambitious to merge other disciplines in natural science. For example, quantum mechanics merged chemistry and chemistry became a part of physics. After the birth of the theory of relativity, astronomy became a part of physics. Almost all disciplines were included in physics. Learn about mergers. Physics also has an ambition to merge with life sciences. As we all know, the famous physicist Schr?dinger wrote the book "What is Life", which has a long-lasting influence. He intended to use the theories and techniques of physics
, merged the life sciences, but in the end it was unsuccessful because there are three gaps in the essential issues between physics and life sciences: The first is that life phenomena are hereditable and dynamic, while physical phenomena are not, and the outcome of physics is Balance and stillness, when an object is thrown out and given kinetic energy, it can roll, but the ending will inevitably stop; secondly, a life phenomenon has a purpose, and its result determines the life process. For example, a person will inevitably die at a certain time. Human beings must embody some physiological characteristics in the life process, and animals also have their own laws. This is the purpose of life phenomena, but physics is not. Physics is where initial conditions determine its results; third, the most important thing about life phenomena is One of the characteristics is that it is holistic and comprehensive. Life phenomena are the result of overall synthesis, while physics is a simple superposition of various parts and events. Therefore, these basic life phenomena determine that physical science cannot merge with life science. Therefore, in the middle of this century, a situation emerged in which physical science and life science coexisted. In the second half of this century, life science began to form a climate. As we all know, the DNA double helix structure in the 1950s ushered in a new era of molecular biology, followed by genetic engineering in the 1970s, research on disease mechanisms in the 1980s (such as research on tumor mechanisms, and the application of monoclonal antibodies in medicine), and in the 1990s The research on the genome of the 1990s has pushed life science to a new peak at a deeper level. The human genome is a subject or a topic in life science that embodies the most fundamental mechanism or the most fundamental foundation of life phenomena. , is the forefront of life sciences. Human genome research will bring about a new leap in biology and will have a greater impact than physics, because physical science elucidates the laws of material activities, while human genome research in life sciences will elucidate the most complex aspects of human beings. The rules for the use of life information are completely different. The impact of human genome research on us in all aspects far exceeds the impact of physics at the beginning of this century. 2. What does the accurate map of the human genome bring to us? Human genome research will bring us new concepts, new methods, and new ways to understand life phenomena. This is crucial for those who engage in scientific research and provides philosophical guidance. Natural science research is equally important.
The new concept that human genome research has given us is to look at the structure, phenomenon and function of the genome as a whole. As we all know, after geneticists proposed genes, we did not know what genes were for a long time. Since geneticists proposed the concept of genes in the last century, we knew the chemical nature of genes in the 1940s, and the structure of genes in the 1950s. In the 1990s, everyone knew When studying genes, what medicine is most interested in is which disease is related to which gene. For a long time, such a linear thinking model has been formed in the medical community. For example, oncologists are committed to finding the oncogenes of certain tumors and researching Such research on the relationship between the two and the high and low levels of gene expression continued for twenty or thirty years. Later, everyone discovered that it was never possible to draw correct conclusions because the disease is complex and is the result of an overall synthesis, not just a simple one. a one-to-one, linear relationship. This cannot help but cause us to reflect. At present, in the scientific community, Western reductionism is still used, and reductionism dominates epistemology. However, diseases are comprehensive and must be understood using comprehensive methods.
Famous oncologist and Nobel Prize winner Du Bok believes that it is not feasible to study tumors in this way. It must be studied at the overall level of the genome. The one-to-one linear thinking research model will not work. One of the biggest characteristics of the linear thinking method in methodology is Workshop-style research involves working in one laboratory after another, and each person is doing experiments one by one, in a piecemeal manner. Therefore, Du Bok proposed that the human genome should be clarified first, and other problems can be solved easily. In 1986, he officially published an article, now called the first bid document of the Human Genome Project (HGP), which mainly solved two problems: (1) Methodology, that is, solving quantitative and qualitative problems in an overall comprehensive manner. In the past, The reductionism is not in line with the current holistic research, and there must be a fundamental change in methodology. The quantity is no longer the quantity produced by the workshop-style research method, but mass production, turning the laboratory into a workshop, into industrialization and automation. Now, in developed countries such as Europe and the United States, the genome laboratory is a workshop where data is mass-produced and fully automated. One technician can manage hundreds of machines and analyze life processes from a comprehensive perspective. Qualitatively, fundamentally change the way of going it alone in the past. It is no longer about the relationship between a certain disease and a certain gene or a certain gene and a certain life phenomenon, but about studying the network of these related genes. Function, function is function, this is the essence. Therefore, human genome research pays more attention to the study of network effects in terms of methodology. Human genome research has transformed from single linear thinking in the past to comprehensive analytical thinking. In terms of methodology, the professional term is high-throughput, that is, batch production, large-scale , networked, therefore, the change in methodology caused the industrial revolution and scientific research revolution, and brought about a series of chain reactions. Data came out in batches, but manual analysis was impossible, and everything had to be solved on computers. The data produced in batches is biological information. The processing of this biological information cannot be solved by manual methods. Computer informatics methods can help us analyze the problem. Bioinformatics will trigger an explosion of information and knowledge in the next century. The biggest inspiration that human genome research has given us is to think about problems from a philosophical perspective, which has given us a conceptual impact and promoted new scientific research methods. (2) Epistemology. In the past few years, other disciplines in the life sciences such as physiology, pathology, pathophysiology and other disciplines complained that there seemed to be an unwritten "rule" that applications for national funds must include genetic work and molecular biology. Work, otherwise it will be difficult to apply for funds. As we all know, there are certain laws in the development of disciplines. The natural sciences, from taxonomy to morphology to genetics, are inevitable laws of historical development. In terms of research methods, they are anatomy, cytology, and molecules. Combining the methods of genetics and molecular science is molecular genetics, and molecular genetics is molecular biology. The current frontier of the discipline is here. If you cling to traditional and classic disciplines, there will be only a dead end. In the 21st century, if your research is not multidisciplinary at the gene level, cell level, overall level, structure and function relationship level, genotype and phenotype level, signal transmission and effect level, it will be difficult to carry out your work. The current trend is obvious. All countries regard HGP as the top priority of their science and technology development strategies in the early 21st century.
When we held a symposium on China-US 21st Century Biomedical Development Strategies in the United States last year, the then NIH director Vamos (who won the Nobel Prize for discovering oncogenes) proposed the 21 There are four key areas for the development of NIH at the beginning of this century, namely: (1) functional genomics; (2) bioinformatics; (3) research on the mechanisms and prevention of major diseases. For the United States, infectious diseases (AIDS) are the The focus; (4) Ethics research in medicine.
3. Will an accurate map of the human genome really bring us more benefits or harms?
According to my experience, HGP research will bring us many benefits: (1) unlimited business opportunities and unlimited bright prospects for scientific development, which will bring good news to human health and health care; (2) HGP research is the same as any other scientific research Likewise, it is a double-edged sword, a Pandora’s box, with advantages and disadvantages, but the advantages far outweigh the disadvantages. The advantages are as follows: We can compare HGP to infrastructure. In a modern city, infrastructure is very important. If the city's infrastructure is not good, the city will be paralyzed and the city's functions will not be able to perform well. HGP research is the infrastructure of life sciences. In scientific language, it is genetic background. Genetic background includes two meanings. One is genetics. Hardware, the other is genetic software, hardware is infrastructure, just like streets, buildings, etc. in a city. Without hardware, software cannot be applied. With hardware and without software, functions cannot be performed. Software is to convert facilities into functions. HGP’s hardware It is a draft, a frame diagram and a full sequence diagram of the sequence. It is the draft and framework diagram of the full sequence of the human genome that the six HGPs jointly announced on June 26. Such a framework diagram is a "heavenly book" that we cannot understand. The current job is to turn it into a function that is understandable and tangible.
So, the first thing that can be seen from HGP research is the benefit. The benefit includes two aspects. One is the scientific benefit, which helps us understand the mechanism of disease. HGP research allows us to have a better understanding of the concept of disease. A brand new change is that all human diseases are genetic diseases. This view once again pushes genetics one step further. Classic genetics only notices that something is inherited, and cannot explain its mechanism at the molecular level. Now genome research has pushed genetics to a new level, which is called genetics. In other words, we can regard all human diseases as genetic diseases. Genetic diseases are divided into single-gene diseases, polygenic diseases, and acquired diseases. Genetic disease. There are more than 6,000 types of single-gene diseases, which are genetic diseases. Relatively speaking, more is known about them, and it is easier to understand their mechanisms. Polygenic diseases include tumors, cardiovascular and cerebrovascular diseases, hypertension, diabetes, rheumatism, mental and neurological diseases and other diseases that humans cannot currently solve. Acquired genetic diseases include diseases caused by pathogenic microbial infections such as AIDS and hepatitis B. Currently, most international competition is at the level of polygenic diseases. Understanding the susceptibility genes (or disease-causing genes) of any disease can not only help understand the mechanism of the disease, but also provide reference for studying other disease-related genes. The mechanism of disease mainly includes genetic mechanism and post-genetic mechanism. That is to say, the occurrence of any disease first directly or indirectly passes through the genetic link, and then passes through the extra-gene link, that is, the pathophysiological or pathological process, until the morphological and phenotypic changes. Therefore, Understanding the genetic mechanisms of disease is crucial. Understand the pathogenesis through genes and contribute to the understanding of diseases. Second, it can immediately turn into economic and social benefits. This is why HGP has attracted special attention and is also a point of contention among people. Because the ultimate goal of HGP is to improve human health and improve the quality of life. In other words, as long as a gene is beneficial to health, it is useful. A gene is a treatment and prevention plan. A gene is a target, which can be turned into a treatment. program, doctors can design treatment and prevention programs based on the function of genes. In addition, target genes can be turned into drugs, drugs can be designed, and drugs can be screened. Pharmacogenomics is now very promising. On the one hand, pharmacogenomics can produce drugs based on the function of a certain gene. On the other hand, it can design personalized treatments based on the polymorphisms of such a gene in different individuals. For example, there is a type of mixed-function oxidase called p450 in the human body. After any external drugs or chemicals enter the body, the first step is activated by p450 into active substances, and then the next step is carried out. Because p450 is polymorphic, It works differently in different individuals, so each individual's response to drugs or chemicals is also different. This is an important reason why the same drug is effective in one person but not in another. HGP research can provide a lot of such information, based on which individualized treatments can be designed and implemented. The human genome itself is a technology platform. Its main forms of expression are genetic information and biological information. This information can be turned into light, electricity, color, and various visible and tangible signals, so that industrialization can proceed. Materials The industry can develop nanotechnology, biomaterials, biochips, and combinatorial chemistry based on genomic information. These are industries that are widely used in medicine and clinical applications. With the progress of HGP in the 21st century, it can be said that one gene can become a sunrise industry.
There is already such a precedent. In foreign countries, if a gene is related to signal transduction, then a series of its products will follow. There are many targets involved in the signal transmission process, and drugs can be designed for each target. Therefore, genetic research has great potential. Unlike color TV, once it is saturated, there is no room for development. A lot of biological information we provide provides a basis for the development of new energy sources. The integration of electronic information has a certain limit, but the integration of biological information is even greater. Biological computers will inevitably replace electronic computers in the 21st century. Biological information can be digitized and can affect all areas of society. In the future, genomic information can be converted into numbers. Medicine in the 21st century is genomic medicine. Everyone has a disk that records his or her genetic information. The doctor can give him a hint or a prediction based on the local situation at that time and his genetic background. Doctors must change the current classic model of treating patients. . If clinicians have little or no knowledge about genomes, it will be detrimental to the development of future medicine.
Since the human genome map is so closely related to human survival, life, and health, with human intelligence, it is possible to transform the information of the genome map into resources beneficial to human survival, life, and health, so that It is inexhaustible and can benefit mankind continuously. Therefore, today, when we have seen that the genome map has illuminated the dawn of hope for mankind, we have reason to believe that the 21st century will be a century of life sciences dominated by genomics. Genomics research can be roughly divided into two major stages: structural genomics research and functional genomics research. The "Human Genome Project", an international large-scale scientific project carried out in the 1990s, is a structural genomics research. After entering the 21st century, functional genomics research will become the focus of research and competition. This is because once the genome expression profile and gene expression profile are known, functional genomics research will become the focus of research and competition. function, we can quickly transition to development and application research based on gene profiles and functions, until we can solve various difficult clinical problems and people's survival, life and health care problems, such as environmental problems, nutritional problems, and disease prevention problems. etc. Since the above research and application involve a wide range of theoretical, technical and resource issues, they can also drive the development of mathematics, physics, chemistry, heaven, earth, biology, information, materials, environment, agriculture, medicine and other disciplines. Because of this, we can almost say that the 21st century will be a century of grabbing genes and a century of brilliant prospects for applying genes to benefit mankind. For this reason, not only developed countries, but also some developing countries, when formulating science and technology development strategies for the 21st century, all regard human genome research as a priority area to invest and support in order to occupy a commanding heights of science and technology in the 21st century. , should at least share a piece of the "cake" of the results created by functional genomics research. You may not have noticed that the United States, the largest technological country in the world, is leading the way and is ambitious to continue to dominate the field of genome mapping in the 21st century. This can be seen from President Clinton’s science and technology development report to Congress in the 21st century science and technology development plan for the United States. This development strategy report titled “Shaping Science and Technology in the 21st Century” determines the direction of scientific research in the United States in the 21st century. There are five main areas of research, one of which is "Advancing Medicine through Genetic Mapping Research". The goal of this main area of ??research is to "help scientists understand disease, health (such as growth and development) processes from a genetic perspective, and how the immune system recognizes foreign invaders." "Once the genetic basis of a disease is discovered, scientists may be able to defeat it." Therefore, genome mapping will directly bring benefits to humans in terms of determining genetic risk, genetic diagnosis, treatment and prevention. Some people estimate that genomics is bound to form a "sunrise industry" in the 21st century and directly participate in market economic activities.
Since genome map research has shown such a bright prospect, why are we still hesitating?
4. The human genome (map) and genes are natural and objective existences, whether you like them or not. Like it, no matter how you look at it. What does the genome give you? What does it give me? What does it give him? The answer is now available: the genome gives us all a genetic background. What is the use of genetic background? It’s a long story. Briefly speaking, from a large perspective, it serves as a carrier of genetic information and uses an information control mechanism to stipulate that we humans can only be humans and nothing else. Animals or plants or microorganisms. The so-called "you will reap melons if you sow melons, and you will reap beans if you sow beans" or "dragons will give birth to dragons, phoenixes will give birth to phoenixes, and mice will give birth to burrows in the ground" are the functions of their respective genomes.
From a small perspective, a person's birth, growth, old age, illness, and death are closely related to the genome expression profile. Can we say that it is not important?
However, for people, the genetic background seems to be "immediately obvious." Dark", "near and far". "It is clear and recent": It is now known that genetic heterogeneity exists in the population. When it is broken down to each individual, the genetic background is more or less different. This difference makes each individual's response to environmental factors (chemical (physical, biological) and psychological factors vary widely. For example, you are prone to catching colds, but he is not; taking medicine is effective for you, but not for him taking the same medicine, etc., examples a lot of. It can be seen that genome mapping research is closely related to human survival, quality of life and health, and in some cases plays a key role. However, at present, the genetic background of the genome map is still mysterious and foggy in a large area, and little is known about it. It will take a long time to reveal its true face. This is "dark and far away". Therefore, for the sake of mankind, studying the genome map is indeed a prosperous, long-term and wise move.
There are many problems. The biggest question is: Where does the naturally occurring human genome come from? Is it evolution? Or is it the work of God, the Creator? How should medical philosophers and experts in the dialectics of nature think about it? What kind of arguments should biomedical scientists make?
5 Although genome maps play a key role in expressing life phenomena, they are not the only role. Any life phenomenon is ultimately the result of the interaction between heredity and environment. The interpretation process of life is a "drama" process with complex plots performed by various complex factors on the screen of genetic background. It is very exciting. Heredity is the internal cause, environmental factors are the external factors, and the external factors work through the internal factors. The two are interdependent. Please see, the genome map analyzes the difficult dialectics so clearly and makes science so clear.
So when talking about genome maps and the role of genes, be careful not to go to extremes. Excessively exaggerating the role of genes, or even making unlimited speculations and extensions, can easily fall into the quagmire of "genetic determinism." On the contrary, if we deny the important role (key role) of genes, we will easily fall into the trap of "gene uselessness" and natural nihilism.
It must also be pointed out that the twin sister of "genetic determinism" is "genetic discrimination." This pair of erroneous twin genetic theories has been criticized by history because it provided the "theoretical basis" for Hitler's genocidal policy and caused a historical catastrophe. However, geneticists should hold high the banner of science and speak with science at a higher level - it can be said with confidence that based on the knowledge currently available, at the genome level, humans have only one unique genome. There is complete equality between people. Among the 100,000 genes contained in each person's genome, there will always be some or a few genes that are "fragile" or "abnormal" genes, no matter who they are. Of course, due to the influence of some unpredictable and complex factors, the "fragile" and "abnormal" genes of a small number of people are unfortunately expressed, resulting in illness, disability, and defects. This is not a fault of their genes, but their bad luck, and various bad factors have played a role in them. True dialectics does not deny the fact that in the biosphere of the earth, in order to maintain the overall ecological balance, human beings must not and cannot be overwhelmingly powerful in one direction. The sick, disabled, and deficient people actually bear the "load" that humans should bear in nature. They suffer from the disease on behalf of all mankind, and they should receive the sympathy, understanding, and care of all people without the disease. Just imagine, if they don't get the disease, maybe your and my "fragile" and "abnormal" genes will have their turn to express themselves. Therefore, at the genetic level, people's "heart to heart" is the most powerful weapon to criticize genetic discrimination.
Relatively speaking, the market for "genes are useless" is much smaller, because the advancement of science and technology has repeatedly proved how important genes are. The theory that genes are useless is no longer tenable.
6 With the in-depth development of human genome mapping research and the encouragement of maximum public participation, related ethical, legal and social issues are attracting people's attention. The ultimate goal of genomic research is to maximize human benefits, especially health-related benefits.
Due to the constant emergence of new information, new technologies, new treatments, new drugs, new concepts and other new things in genomic research, it will be difficult to determine their pros and cons within a certain period of time. When using them or studying them, ethics will inevitably be involved. , legal and social issues, such as: privacy issues of genomic genetic information, safety issues in genetic diagnosis, treatment and prevention, issues regarding the right to know and informed consent involving the genome, and the insurance rights arising from these issues, Issues such as the right to work, inheritance rights, reproductive rights, etc. How to ensure that genome mapping research does not harm people's interests or reduces the degree of damage to a minimum? Two approaches can usually be taken: one is ethics and public opinion supervision, and the other is laws and regulations.
Conscience is the most effective ethical norm. Conscience needs to be continuously cultivated, purified and sublimated. For a genetic scientist who is extremely ambitious and curious, he may sometimes go too far and do unethical things. Therefore, he needs to be supervised by public opinion and regulated by laws and regulations.
There is another type of genomic research that clearly goes beyond the ethical scope, and that is the production of genetic weapons. Based on the polymorphic characteristics of the genome of a certain ethnic group, it is possible to create genetic weapons specifically designed to exterminate that ethnic group. This is theoretically and technically established. We oppose this attempt. However, the world is so big that there are always madmen and crazy people. Maybe someone is already developing this new type of weapon. However, in my opinion, whether it is nuclear weapons or genetic weapons, in today's highly developed and developed science and technology, as well as the increasingly rapid exchange of international scientific and technological information, these powerful new weapons mainly only serve as a deterrent force. . Just imagine, if you have genetic weapons, I also have the ability to make them, but the result is that no one dares to use them first. Once any war madman dares to use them, his own fate may not be better.
Genetic weapons involve national security and are closely related to everyone’s safety. This issue should be considered from a strategic perspective. In genomic research, although there are many ethical, legal and social issues, these cannot be a shackles on genomic research. We should firmly believe that out of instinct and rationality for survival and living, human beings will follow certain procedures and often adjust their behavior in any scientific and technological activities without causing trouble. This is the mainstream.