The prospect of genetic engineering The scientific community predicts that 2 1 century will be the century of genetic engineering. Genetic engineering is an artificial intervention in biological inheritance at the molecular level. To understand it, let's start with bioengineering: bioengineering, also known as biotechnology, is a comprehensive engineering technology that uses modern life science principles and technologies such as information and chemical engineering to process cheap raw materials to varying degrees and provide a large number of useful products by using living cells or enzymes produced by them.
The basis of bioengineering is modern life science, technology science and information science. The main products of bioengineering are to provide a large number of high-quality fermented products, such as biochemical drugs, chemical raw materials, energy, biological control agents, food and beverage, etc., and also provide social services for human beings such as environmental management, metal extraction, clinical diagnosis, gene therapy and crop variety improvement.
Bioengineering consists of five parts: genetic engineering, cell engineering, enzyme engineering, protein engineering and microbial engineering. Among them, genetic engineering is that people transform biological genes and use biology to produce special products that people want. With the secrets of the internal structure and genetic mechanism of DNA presented to people bit by bit, biologists are no longer satisfied with exploring and prompting the secrets of biological inheritance, but are eager to try and imagine interfering with the genetic characteristics of organisms at the molecular level.
Gilbert of America is the founder of base arrangement analysis. He took the lead in supporting the human genome project. If a genetic code fragment in one organism's DNA is connected to another organism's DNA chain and the DNA is recombined, can't we design new genetic material and create new biological types according to human wishes? This is completely different from the traditional practice of breeding biological offspring in the past. It is very similar to the engineering design of technical science, that is, according to human needs, this "gene" of this creature and that "gene" of that creature are reconstructed and assembled into a new gene combination to create a new creature. This kind of biological science and technology, which is carried out completely according to people's wishes, is called "genetic engineering" or "genetic engineering"
What is the main course of human genetic engineering? 1866, Austrian geneticist Father Mendel discovered the genetic law of living things. 1868, Swiss biologist Friedrich discovered that the nucleus has two parts: acidity and protein. The acidic part was later called DNA；; 1882, when German embryologist Walter Fleming was studying salamander cells, he found that the nucleus contained a large number of divided linear objects, that is, later chromosomes. 1944, American researchers proved that DNA is the genetic material of most organisms, not protein; 1953, American biochemist Watson and British physicist Crick announced the discovery of the double helix of DNA, which laid the foundation of genetic engineering. 1980, the first transgenic mouse was born; 1996, the first cloned sheep was born; 1999, American scientists cracked the sequence map of the 22nd human genome. The future plan is to prescribe drugs for related diseases according to the genetic map.
Human genome research is the basic research of life science. Some scientists regard genome map as a road map or periodic table in chemistry; Some scientists compare the genome map to a dictionary, but from any angle, in order to promote human health, prevent diseases and prolong life, the application prospect of decoding and deciphering human genetic code is extremely beautiful. After the information of 65,438+10,000 human genes and their corresponding chromosome positions was deciphered, the genetic codes of human beings, animals and plants were deciphered, which opened up broad prospects for overcoming diseases and improving crop yield. It will become the source of knowledge and technological innovation in the pharmaceutical and biopharmaceutical industries. Beckwitz of the United States is observing colonies in a vessel. He once warned about the human genome project.
Scientific research has proved that some major diseases that plague human health, such as cardiovascular and cerebrovascular diseases, diabetes, liver diseases and cancer, are all related to genes. According to the decoded gene sequence and function, we can find out these genes, screen drugs according to the corresponding pathological positions, and even design new drugs according to the existing genetic knowledge, so as to repair or replace these pathological genes and cure persistent diseases. Gene medicine will become a dazzling star in the medical field in 2 1 century. Genetic research can not only provide basic data for screening and developing new drugs, but also provide the possibility for using genes to detect, prevent and treat diseases. For example, people with the same living habits and living environment have different susceptibility to the same disease due to different gene sequences. An obvious example is that some smokers are prone to lung cancer, while others are not. Doctors will give different guidance according to different gene sequences of different people, so that they can develop scientific and reasonable living habits and prevent diseases as much as possible.
With the development of human genetic engineering, decoding all human DNA is just around the corner.
The development of information technology has changed people's life style, and the breakthrough of genetic engineering will help people prolong their life. At present, the average life expectancy in some countries has exceeded 80 years, and China has also exceeded 70 years. Some scientists predict that with the effective treatment of chronic diseases such as cancer, cardiovascular and cerebrovascular diseases, there may be countries with an average life expectancy of more than 1000 years between 2020 and 2030. By 2050, the average life expectancy of human beings will reach 90 to 95 years.
Man will challenge the limits of life science. 1953 One day in February, British scientist francis crick announced that we had discovered the secret of life. He found that DNA is a double helix molecule existing in the nucleus, which determines the inheritance of organisms. Interestingly, the scientist announced this important scientific discovery in a bar in Cambridge. Deciphering the genetic codes of humans, animals and plants has opened up broad prospects for overcoming diseases and increasing crop yield. From 65438 to 0987, American scientists put forward the "Human Genome Project", whose goal is to determine all the genetic information of human beings, determine the specific positions of human genes on 23 pairs of chromosomes, find out the nucleotide sequence of each gene, and establish a human gene bank. 1999, the genetic code of human chromosome 22 was deciphered, and the "Human Genome Project" took a successful step. It can be predicted that in the next quarter century, scientists may reveal about 5,000 pathogenic genes of human genetic diseases, so as to find gene therapy for fatal diseases such as cancer, diabetes, heart disease and hemophilia.
Following the publication of the "working frame map" of the human genome by scientists on June 26th, 2000, scientists from China, the United States, Japan, Germany, France and Britain and Celera Company of the United States jointly published the human genome map and preliminary analysis results on February 2nd, 2006. The human genome map published this time is more accurate, clear and complete on the basis of the original "working frame map" after sorting, classification and arrangement. The human genome contains most of the genetic information of human birth, aging, disease and death. Deciphering it will bring a revolution to the diagnosis of diseases, the development of new drugs and the exploration of new treatments. The publication of human genome map and preliminary analysis results will play an important role in promoting the development of life science and biotechnology. With the further development of human genome research, life science and biotechnology will enter a new era with the new century.
There are at least two strong proofs that genetic engineering has made great progress in the 20th century. One is genetically modified animals and plants, and the other is cloning technology. Transgenic animals and plants have been implanted with new genes, which makes them have brand-new characters that they did not have before, thus causing an agricultural revolution. Now transgenic technology has been widely used, such as insect-resistant tomatoes and fast-growing crucian carp. The birth of cloned sheep was the first of the top ten scientific and technological breakthroughs in the world in 1997. This ewe named Dolly is the first mammal produced by asexual reproduction, and it completely inherits the genetic genes of the ewe that gave it the nucleus. "Cloning" has become the focus of people's attention for a time. Although there are ethical and social problems, the great progress of biotechnology has given mankind a broader imagination space for the future.
Memorabilia of genetic engineering
From 1860 to 1870, Austrian scholar Mendel put forward the concept of genetic factor according to pea hybridization experiment and summarized Mendel's genetic law.
1909, Danish botanist and geneticist Johnson first put forward the word "gene" to express Mendel's concept of genetic factors.
1944, three American scientists isolated bacterial DNA (deoxyribonucleic acid) and found that DNA is a molecule carrying the genetic material of life.
1953, American Watson and Englishman Crick put forward the double helix model of DNA molecules through experiments.
1969 Scientists successfully isolated the first gene.
1980, scientists cultivated the world's first transgenic animal transgenic mouse for the first time.
1983, scientists cultivated the world's first transgenic plant transgenic tobacco for the first time.
1988 K.Mullis invented PCR technology.
1990 10 The International Human Genome Project, known as the Apollo Moon Landing Program in life science, was launched.
From 65438 to 0998, a group of scientists founded Celera Gene Company in Rockwell, USA, to compete with the International Human Genome Project.
1998 12 the complete genome sequence of a small nematode has been determined, which is the first time that scientists have drawn the genome map of a multicellular animal.
1In September 1999, China was allowed to join the Human Genome Project and was responsible for determining 1% of the total sequence of the human genome. China is the sixth country to participate in the international human genome project after the United States, Britain, Japan, Germany and France, and it is also the only developing country to participate in this project.
1 99965438+February1day, the joint research team of the International Human Genome Project announced that the genetic code of the 22nd human chromosome has been completely decoded, which is the first time that humans have successfully completed the determination of the complete gene sequence of the human chromosome.
On April 6, 2000, Celera announced that it had cracked the complete genetic code of an experimenter, but it was questioned by many scientists.
At the end of April 2000, Chinese scientists completed the working framework of 1% human genome according to the deployment of the International Human Genome Project.
On May 8, 2000, German and Japanese scientists announced that the sequencing of chromosome 2 1 had been basically completed.
On June 26th, 2000, scientists published the working draft of human genome, which marked an important step for human beings to interpret their "book of life".
In June 5438+February 65438+April 2000, scientists in the United States and Britain announced that they had drawn a complete map of Arabidopsis genome, which was the first time that human beings had completely deciphered the gene sequence of a plant.
2001February 12 Chinese, American, Japanese, German, French and British scientists jointly published the human genome map and preliminary analysis results.
For the first time, scientists published the draft of "genetic information" of the human genome.
Gene research countries are competing for the global map of the gene age.
Let's take a look at the research on genetic science in countries around the world at the arrival of the new century.
Britain: As early as the mid-1980s, Britain had its first biotechnology enterprise, which was the earliest among European countries. Today, it has 560 biotechnology companies, and Britain accounts for half of the 70 listed biotechnology companies in Europe.
Germany: Recognizing that biotechnology will be the key to maintain Germany's future economic competitiveness, the German government passed legislation in 1993 to simplify the examination and approval procedures for biotechnology enterprises, and allocated1500,000 Deutsche Mark to set up three biotechnology research centers. In addition, the government also plans to spend 654.38+0.2 billion marks on the research of the human genome project in the next five years. 1999, German researchers applied for biotechnology patents, accounting for 14% in Europe.
France: In the past 10 years, the French government's funds for biotechnology have increased by 10 times. The most typical project is the so-called "Gene Valley" Science Park established by 1998 near Paris, where the most promising emerging biotechnology companies in France gather. Another 20 French cities are also planning to set up their own biotechnology parks in imitation of the "Gene Valley".
Spain: Mar Pharmaceutical Company is the representative of this country's biotechnology enterprises, specializing in finding anticancer substances from marine life. Among them, ET-743 is the most valuable one, which is a red anticancer drug extracted from the seabed ejecta in the Caribbean and Mediterranean. ET-743 is planned to be registered and produced in Europe in 2002, and will be used to treat common cancers such as bone cancer, skin cancer, ovarian cancer and breast cancer.
India: The Indian government funds more than 50 research centers across the country to collect human genome data. Due to the unique "caste system" and the intermarriage customs of some remote tribes, the gene bank of Indian population is the most complete in the world, and it is a very valuable database for scientists to find the pathology and treatment of genetic diseases. However, private biotechnology enterprises in India are still in their infancy.
Japan: The Japanese government plans to increase the funding for biotechnology research by 23% next year. A private company has also established the Dragon Gene Center, which will be the largest genome research institution in Asia.
Singapore: Singapore announced a $60 million genetic technology research project to study how diseases have different effects on Asians and whites. The plan focuses on analyzing genetic differences and what treatment methods are effective for Asians, so as to finally gain new knowledge of identifying and treating diseases; And set up high-tech companies to manufacture drugs and medical products derived from this research.
China: Participated in the Human Genome Project and determined the sequence of 1%, which brought a bright future to the bio-industry in China in the 2nd1century. This "1% project" has enabled China to enter the international advanced ranks of bio-industry, and also enabled China to naturally share all the achievements, resources and technologies of the Human Genome Project.
Genetic Engineering and Agriculture, Animal Husbandry and Food Industry
Using genetic engineering technology, we can not only cultivate high-quality, high-yield and disease-resistant crops and new varieties of livestock and poultry, but also cultivate animals and plants with special uses.
1. Transgenic fish
Transgenic fish with fast growth, tolerance to harsh environment and good meat quality (China).
2. Transgenic cattle
Transgenic cattle with human growth hormone in milk (Argentina).
3. Transgenic sweet pepper with cucumber bacterial wilt resistance gene
4. Tomato with fish cold-resistant gene
5. Transgenic potato with cucumber bacterial wilt resistance gene
6. Genetically modified soybeans that will not cause allergies
7. Superanimals
Super sheep and super mouse with storage protein gene introduced
8. Special animals
Pigs and mice with special uses by introducing human genes.
9. Insect resistant cotton
Bacillus thuringiensis can synthesize toxic protein to kill cotton bollworm. Insect-resistant cotton can be obtained by introducing the gene into cotton cells in vitro and then conducting tissue culture.
[Edit this paragraph] Genetic engineering and environmental protection
The DNA probe made by genetic engineering can detect viruses, bacteria and other pollution in the environment very sensitively.
Indicator organisms cultivated by genetic engineering can reflect environmental pollution very sensitively, but they are not easy to die in large numbers because of environmental pollution, and can even absorb and transform pollutants.
Genetic engineering and environmental pollution control
The "super bacteria" produced by genetic engineering can devour and decompose a variety of substances that pollute the environment.
Usually, a bacterium can only decompose one hydrocarbon in oil, but the "super bacteria" successfully cultivated through genetic engineering can decompose many hydrocarbons in oil. Some can also swallow and transform heavy metals such as mercury and cadmium and decompose toxic substances such as DDT. )
Gene therapy can wait for the arrival of medical revolution.
"Gene" means the word "gene" that we often see now, which is the most basic factor that determines all life phenomena of a biological species. Scientists believe that the translation of this word is not only fluent in sound, but also appropriate in meaning, and it is a model of foreign language translation of scientific terms. As the genetic unit in the body, gene can not only determine our appearance and height, but also its abnormality will inevitably lead to various diseases. Some defective genes may be passed on to future generations, while others will not. Gene therapy was originally proposed for genetic diseases with single gene defect, aiming at replacing the defective gene with a normal gene or remedying the pathogenic factors of the defective gene.
Using genes to treat diseases is to introduce functional genes into patients for expression. The disease can be treated because the expression product-protein has played a role. The result of gene therapy is like an operation on a gene, which can cure the disease and remove the roots, so some people describe it as "molecular surgery".
We can divide gene therapy into two types: sex cell gene therapy and somatic cell gene therapy. Sex cell gene therapy is to operate in patients' sex cells so that their offspring will never get this genetic disease again. Somatic gene therapy is the mainstream of gene therapy research at present. However, its shortcomings are also obvious. It has not changed the genetic background of patients with single or multiple genetic defects, so that some people's offspring will inevitably suffer from this disease.
No matter what kind of gene therapy is in the initial stage of clinical trial, it has no stable curative effect and complete safety, which is the current research status of gene therapy.
It can be said that it is quite dangerous to carry out gene therapy before fully explaining the operating mechanism of the human genome and fully understanding the gene regulation mechanism and the molecular mechanism of diseases. It is particularly important to enhance the safety of gene therapy and improve the rigor and rationality of clinical trials. Although there are still many obstacles to overcome in gene therapy, the general trend is encouraging. According to statistics, as of the end of 1998, 373 clinical bills have been implemented in the world, and 3 134 people have accepted gene transfer experiments, which fully shows its great development potential and application prospect. As predicted by the founder of gene therapy, the emergence of gene therapy will promote the revolutionary changes in medicine in the new century.
[Edit this paragraph] Genetic engineering has brought Chinese medicine into a new era.
China expert 65438+65438, who attended the international symposium on "Traditional Chinese Medicine and Natural Medicine" on May 3rd, thinks that the research on transgenic medicinal plants or organs, the cloning of key enzyme genes of effective secondary metabolism pathway, the molecular markers of traditional Chinese medicine and the research on gene chip of traditional Chinese medicine have become the hot spots in the research of traditional Chinese medicine, which will bring traditional Chinese medicine into a brand-new era.
According to Guo De 'an, deputy director of the State Key Laboratory of Natural Medicine and Biomimetic Medicine in Peking University, the research on transgenic medicinal plants or organs and tissues is one of the more active fields in biotechnology of traditional Chinese medicine in recent years.
In the research of transgenic medicinal plants, the Institute of Medicinal Plants of China Academy of Medical Sciences used Agrobacterium rhizogenes and Agrobacterium tumefaciens to induce Salvia miltiorrhiza to form hairy roots and crown gall, and then differentiated into plants. They made a comparative study on the morphology and chemical composition between them and cultivated salvia miltiorrhiza. The results showed that the leaves of plants regenerated from hairy roots were shriveled, internodes were shortened, plants were dwarfed and fibrous roots were developed. However, the crown gall tissue regenerated plants have tall plant type, developed root system, high yield and higher tanshinone content than the control, which is of great significance for salvia miltiorrhiza breeding and improving the quality of medicinal materials.
Guo Dean said that studying the biosynthetic pathway of chemical components of traditional Chinese medicine not only contributes to the bionic synthesis of these chemical components, but also can artificially regulate the synthesis of these chemical components, which is conducive to the directional synthesis of the required chemical components. Domestic research in this field has begun.
It is understood that the application research of biotechnology in Chinese medicine research is gradually emerging. Some aspects, such as tissue and cell culture of medicinal plants, have accumulated 20 or 30 years of experience, and the theory and technology are quite mature, which has formed a certain scale in the country. Among them, the research on cell engineering of Chinese herbal medicine is in its heyday.
Guo Dean said that in the face of the problem that many wild plants are on the verge of extinction and it is difficult to introduce in some special environments, Chinese scientists have begun to explore the production of useful secondary metabolites by cultivating a large number of higher plant cells and organs. The research contents include the screening of high-yield tissues or cell lines, the optimization of culture conditions and the regulation of biosynthesis pathway of secondary metabolites in order to reduce costs and improve the yield of secondary metabolites.
In addition, the research on biotransformation of exogenous chemical components by using plant suspension cultured cells or adventitious roots and hairy roots has also quietly emerged recently, and some progress has been made.
Moreover, scientists pay more attention to the regulation of biosynthesis pathway of secondary metabolites. These studies have achieved exciting results, indicating that the cell culture of medicinal plants in China has entered a new era.
Guo Dean believes that the main research direction in the future should focus on tissue cell culture of precious and endangered medicinal plants; Regulating the production of secondary metabolites; Biotransformation of some important chemical components in traditional Chinese medicine. In addition, the biotechnology research of animal medicine should be strengthened.
[Edit this paragraph] Genetic Engineering and Medicine and Health
1. Production of genetically engineered drugs:
Many drugs are produced by biological tissues. Limited by the source of materials, the output is limited and its price is often very expensive.
Microorganisms grow rapidly and are easy to control, which is suitable for large-scale industrial production. If the genes that biosynthesize the corresponding drug components are introduced into microbial cells to produce the corresponding drugs, not only the yield problem can be solved, but also the production cost can be greatly reduced.
(1) genetically engineered insulin
Insulin is a specific drug for treating diabetes. For a long time, it can only be extracted from the pancreas of pigs, cattle and other animals. 100Kg pancreas can only extract 4-5g insulin, and its low yield and high price can be imagined.
Introducing synthetic insulin gene into E.coli can produce 100g insulin per 2000L culture medium! Large-scale industrial production not only solves the problem of drug output that is more expensive than gold, but also reduces the price by 30%-50%!
(2) genetically engineered interferon
Interferon is simply a "panacea" for treating viral infections! It used to be extracted from human blood, and it takes 300L of blood to extract 1mg! Needless to say, its "precious" degree.
Genetically engineered human interferon α-2b (Andafen) is the first domestically engineered human interferon α-2b in China, which has the functions of antivirus, inhibiting tumor cell proliferation and regulating human immune function. Widely used in the treatment of viral diseases and various tumors, it is currently recognized as the first choice drug for the treatment of viral diseases and the main drug for tumor biotherapy.
⑶ Other genetically engineered drugs.
The industrial production of artificial blood, interleukin and hepatitis B vaccine through genetic engineering has played an important role in alleviating human suffering and improving human health.
2. Gene diagnosis and gene therapy:
Using the "DNA probe" designed and manufactured by genetic engineering to detect viral infections and genetic defects such as hepatitis virus is not only accurate, but also rapid. By introducing normal genes into patients with genetic diseases through genetic engineering, the pain of patients can be relieved at one time.
◆ Gene engineering therapy of ◆SCID
Patients with severe combined immunodeficiency (SCID) lack normal human immune function. As long as it is slightly infected by bacteria or viruses, it will die. The pathogenesis of this disease is the mutation of the gene encoding adenosine deaminase (ada) on the cell autosome. It can be treated by genetic engineering.
Genetic Engineering —— Transgenic Animals Producing the Most Effective Drugs
Transgenic animals are an individual expression response system, which represents the latest achievements in drug production in the present era and is also the most complex and promising biological response system. As far as gene drugs are produced by transgenic animals and livestock, the ideal expression site is mammary gland. Because mammary gland is an exocrine organ, milk does not enter the internal circulation, which will not affect the physiological and metabolic reaction of transgenic animals themselves. The gene product obtained from transgenic animal milk is not only high in yield and easy to purify, but also the expressed protein has been fully modified and has stable biological activity, so it is also called "animal mammary gland bioreactor". Therefore, using the mammary glands of transgenic cattle, sheep and other livestock to express the protein gene needed by human beings is equivalent to building a large pharmaceutical factory, which obviously has the advantages of less investment, high efficiency and no pollution.
From the biological point of view, the utilization and conversion efficiency of energy by living organisms is beyond the reach of any mechanical device in the world today. Therefore, the production of drugs through transgenic animals is the most effective and advanced system that people can imagine so far.
Mammary gland of transgenic animals can continuously provide the production of target gene (drug protein), which not only has high yield, but also has stable biological activity after full modification and processing. As a bioreactor, transgenic movement can reproduce indefinitely, so it has the advantages of low cost, short cycle and good benefit. Some drug proteins isolated from the milk of genetically modified livestock are being used in clinical trials.
At present, China has obtained transgenic mice, rabbits, fish, pigs, sheep and cattle in the field of transgenic animal research. In 1990s, the research of transgenic goat mammary gland bioreactor was listed as a major project of the national "863" high-tech plan.
Although the drugs produced by transgenic animals (livestock)-mammary gland bioreactor or precious protein have not yet formed an industry, according to foreign economists' prediction, the drugs produced by transgenic movement will stand on the world market in about 10 years. At that time, the annual sales of drugs alone exceeded $25 billion (excluding nutritional proteins and other products), making the transgenic animal (livestock)-breast bioreactor industry the most profitable new industry.
From June 5438 to February 25, 2000, the appearance of three transgenic sheep in Beijing and various transgenic vegetables, rice and cotton before that made people pay more attention to transgenic technology. So what kind of mysterious technology is transgenic technology?
Mr. Guan Tian, chief animal husbandry officer of Beijing Xingluyuan Biotechnology Center, the third high-tech agricultural experimental demonstration zone in Shunyi District, Beijing, said that the significance of transgenic animals and transgenic sheep lies not in the sheep itself, but in the fact that the goat milk they produce can extract α antitrypsin, and each of them can be called a natural gene pharmaceutical factory with great value.
Mr. Zeng, an academician of China Academy of Engineering and director of Shanghai Institute of Medical Genetics of Shanghai Children's Hospital, believes that transgenic animals refer to a kind of animals in which genes of animals or humans that people want to study, or drug protein genes with economic value, are artificially introduced into fertilized eggs (or early embryonic cells) of animals, and integrated with the genome of the animals themselves, so that the foreign genes proliferate with cell division and are stably passed on to the next generation.
According to Mr. Tian, the preparation of transgenic sheep is to inject human α antitrypsin gene into the male nucleus of ewe fertilized egg through micro-operation, and integrate it with sheep's own gene to form an inseparable whole. This new genome can be stably passed on to the born lamb. Goats have also become a new strain created artificially, which is different from female goats, and their offspring will also carry this α-antitrypsin gene. This process includes the grafting of some similar plants.
Preparing transgenic animals is a complex task. At present, in the development of transgenic animals, the integration rate of foreign genes with the animal's own genome is low, and their expression is often not ideal, and the inherent characteristics of foreign genes can not be fully expressed or expressed. The integration rate of experimental sports such as cattle, sheep and pigs is generally around 1%. There may be many reasons for this. The first is the problem of target gene. The expression level of different foreign genes is different and varies from person to person. Secondly, whether the combination and connection of the internal parts of the foreign gene expression vector are reasonable; More importantly, whether it is reasonable for foreign genes to reach the integration position in the animal genome. Scientists don't know where the expression of integration is high and where it is low. People can't control the position of foreign gene integration, so they can only integrate randomly. Therefore, the low integration rate is inevitable.
Although there are still some technologies that need to be solved urgently, the great progress in the research of transgenic animals, especially its wide application in various fields, has had a far-reaching impact on biomedicine, animal husbandry and pharmaceutical industry.