The relationship between the birth of genetic engineering and related disciplines[3]
Genetic engineering（geneticEngineering)geneSplicing technology andDNA recombination technology。The so-called genetic engineering is a complex technology to operate genes at the molecular level, which is to introduce foreign genes after recombination in vitroReceptor cellThe operation that enables this gene to replicate, transcribe, translate and express in receptor cells.
Genetic engineering isbioengineeringAn important branch ofcell engineering、Enzyme engineering、Protein Engineeringandmicrobial engineeringTogether, it forms bioengineering.The so-called genetic engineering is a complex technology that operates genes at the molecular level.It is the genetic material of a donor organism that is needed by artificial means——DNAMacromolecules are extracted, and appropriatetool enzymeAfter cutting, connect it with theDNA moleculeConnect, and thencarrierIt is a new technology to introduce foreign substances into a receptor cell that is easier to grow and reproduce, so that foreign substances can "settle down" in it, replicate and express normally, and obtain new species.It overcameDistant hybridizationThe incompatibility barrier of.
Recombinant DNA technologyIt refers to the DNA in vitro operation procedure that splices and recombines the genes and vectors of one organism (donor) in vitro, and then transfers them into another organism (receptor), so that they can stably inherit and express new products or new traits according to people's wishes. It is also calledmolecular cloningTechnology.Therefore,donor、recipient. The carrier is recombinationDNAThe three basic elements of technology.
Basic definition of genetic engineering
In a narrow sense, it only refers to genetic engineering.
It refers to an organism（donor）In vitroSplicingRecombination, and then transfer into another organism (receptor), so that it can stably inherit according to people's wishes, and express new products or new traits.
recombinationDNA moleculeIt needs to be replicated and expanded in receptor cells, so genetic engineering can also be characterized asmolecular cloning(Molecular Cloning) orGene cloning（Gene Cloning）。
MeansDNA recombination technologyThe industrial design and application of, including upstream technology and downstream technology two major components.
Upstream technology:Gene recombination、cloneAnd expression design and construction (i.eDNA recombination technology）；
Downstream technology: large-scale cultivation of genetically engineered bacteria (cells), exogenousgene expressionThe separation and purification process of the product.
The broad concept of genetic engineering is more inclined to the category of engineering.
Genetics engineering in a broad sense is a highly unified entity:
The design of upstream recombinant DNA must be guided by simplifying the downstream operation process and equipment;
The downstream process is the embodiment and guarantee of the upstream restructuring blueprint---The basic principles of genetic engineering industrialization.
Genetic engineering refers toRecombinant DNA technologyThe industrial design and application of, including upstream technology and downstream technology two major components.Upstream technology refers to the design and construction of gene recombination, cloning and expression (i.e. recombinant DNA technology);The downstream technology involvesGenetically engineered bacteriaOr large-scale culture of cells or genetically engineered organisms, andGene productThe separation and purification process of.
Genetic modification
Genetic engineering is the use of recombination technology, in vitro through artificial "cutting" and "splicing" and other methodsBiologyThe nucleic acid (gene) ofEukaryotic cellThe recombinant gene can be expressed in cells to produce theGene productOr to transform and create new biological types.
Essentially, the definition of genetic engineering emphasizes exogenousDNANew combinations of molecules are introduced into a new host organism for reproduction.This new combination of DNA molecules is designed and operated according to engineering methods, which endows genetic engineering with the ability to cross the natural species barrier and overcome the inherentBiological speciesThe greatest feature of genetic engineering is the restriction between (specifications), which expands and brings the possibility of directional transformation of organisms.
Genetic engineering includes manually connecting genes from different organisms with carrier DNA with the ability of self replication in vitro to form new recombinant DNA, which is then sent to the recipient organism for expression, thus generating the transfer and recombination of genetic material.
A complete genetic engineering technology program for production purposes includes the following basic contents: (1) Isolation and cloning of foreign target genes, as well as structure and function research of target genes.This part of the work is the basis of the whole genetic engineering, so it is also called the upstream part of genetic engineering.(2) It is suitable for transfer, construction of expression vector or recombination of expression regulation structure of target gene.（3）foreign geneImport of.(4) Exogenous gene inhostgenomeThe integration, expression and detection of DNA and the screening of transgenic organisms.(5) Verification of physiological function of foreign gene expression products.(6) Breeding and establishment of new transgenic lines, and benefit analysis of new transgenic lines.(7) The establishment of ecological and evolutionary security mechanism.(8) Consumer safety evaluation.
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1) Transspecies
foreign geneTo reproduce in a different biological cell.
The most prominent advantage of genetic engineering is that it breaks the boundaries between species that are difficult to break through by conventional breeding, and can makeprokaryoteAndEukaryoteBetweenanimalAndBotanyBetween humans and other creaturesgenetic informationRestructuring and transfer.Human genes can be transferred toEscherichia coliMedium expression,BacteriaThis gene can be transferred to plants for expression.[1]
Genetic engineering ismolecular biologyIt is a new biotechnology science born in the 1970s based on the comprehensive development of molecular genetics.This definition shows that genetic engineering has the following important characteristics: first, exogenousnucleic acidMolecules in differenthostThe ability to reproduce in organisms can cross the barrier of natural species and put genes from any kind of organism into new organisms, which can have no kinship with the original organism. This ability is the first important feature of genetic engineering.The second feature is that a certain small segment of DNA is amplified in a new host cell, so that a small number of DNA samples can "copy" a large amount of DNA, and a large number of absolutely pure DNA molecular groups that do not pollute any other DNA sequence.Scientists call the technology of changing the DNA of human germ cells "germline therapy", and the commonly said "genetic engineering" is aimed at changing the germ cells of animals and plants.No matter what the name is, changing the DNA of an individual's germ cell will probably cause the same changes to its offspring.
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At the beginning of the 20th century, genetic engineering has not yet been applied to human body, but it has been applied tolivestockAlmost all non-human life objects have done experiments and achieved success.In fact, all are used for treatmentdiabetesOfinsulinThey all come from a bacteriumDNAThe gene that can produce insulin in human being is inserted into, and bacteria can reproduce insulin by themselves.Genetic engineering technology enables many plants to have the ability of resistance to pests and herbicides;In the United States, about half of soybeans and a quarter of corn are genetically modified.Whether genetically modified animals and plants should be used in agriculture has become the focus of debate: supporters believe that genetically modified agricultural products are easier to grow and contain more nutrients (even drugs), which will help alleviate famine and disease worldwide;Opponents believe that the introduction of new genes into agricultural products will cause side effects, especially environmental damage.
Admittedly, the function of many genes and the way in which they work together are still unknown to human beings. However, many people hope that the use of genetic engineering can make tomatoes have anti-cancer effects, make salmon grow several times larger than in nature, and make pets no longer cause allergies.After all, embryosGenetic disease screening, gene repair and genetic engineering can not only be used to treat diseases, but also to change the color of eyesintelligenceAnd other human characteristics.We are far from designing and customizing our offspring, but there have been examples of cultivating the physical characteristics people need with the help of embryonic genetic disease screening technology.For example, using this technology, the parents of the child can have a child that matches the bone marrow of the child, and then cure the child through bone marrow transplantation.
As the secrets of the internal structure and genetic mechanism of DNA are presented to people little by little, especially when people understand that the genetic code is composed ofRNAAfter transcriptional expression,biologistNo longer satisfied with exploring and revealing the secrets of biological heredity, but began to be eager to try to interfere with biological genetic characteristics at the molecular level.If a genetic code segment in the DNA of one organism is connected to the DNA chain of another organism and the DNA is reorganized, new genetic materials can be designed and new biological types can be created according to human wishes, which is completely different from the traditional practice of cultivating the offspring of biological reproduction in the past.This is likeTechnical scienceAccording to human needs, this "gene" of this creature and that "gene" of that creature are reconstructed,Biological Science and TechnologyIs called "genetic engineering", or“genetic engineering”。The basic operation steps are in vitroRecombinant DNAProcess.First selectTarget geneSuitable means of delivery, such asplasmid、VirusesWait, then use the sameRestriction enzymeCut the carrier and target gene respectively to make them produce the same sticky end, and then add an appropriate amount ofDNA ligase, combine the DNA of the target gene and the DNA of the carrier outside the organism to formRecombinant DNA(or recombinant plasmid) Transfer the recombinant DNA hybrid molecules to the selected biological cells by the way of bacterial or viral infection, so that the recombinant DNA can be copied, transcribed and translated in the receptor cells.In the process of loading the target gene on the carrier and transporting the target gene to the receptor cell through the carrier, in general, the success rate of transformation is only 1%.HereditaryengineerThey created the method of treating receptor cells with calcium chloride under low temperature and increasing the concentration of recombinant DNA to improve the transformation rate.The chloride calcification treatment can increase the cell wall permeability of receptor cells, thus making hybrid DNA molecules easier to enter.Also availablegene gun Laser microbeam perforation methodMicroinjectionAnd other methods to directly transfer the target gene into receptor cells (such asZygoteCells).
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UK: As early as the mid-1980s, the UK had its first biotechnology enterprise, which was the earliest developed country in Europe.Now it has 560 biotechnology companies, and the UK accounts for half of the 70 listed biotechnology companies in Europe.
Germany: Recognizing that biotechnology will be the key to maintaining Germany's future economic competitiveness, the German government passed legislation in 1993 to simplify the approval procedures for biotechnology enterprises, and allocated 150 million marks to establish three biotechnology research centers.In addition, the government plans to spend 1.2 billion marks in the next five years for the research of the Human Genome Project.In 1999, the biotechnology patents applied by German researchers accounted for 14% of Europe's patents.
France: In the past 10 years, the French government has increased its funds for biotechnology by 10 times. The most typical project is the science and technology park called "Gene Valley" established near Paris in 1998, where the most potential emerging biotechnology companies in France are gathered.Another 20 French cities are also preparing to build their own biotechnology parks following the example of "Gene Valley".
Spain: Mal Pharmaceutical Company is the representative of biotechnology enterprises in the country. The company specializes in finding anti-cancer substances from marine organisms.One of the most valuable is ET-743, which is a red anti-cancer drug extracted from the submarine ejecta of the Caribbean Sea and the Mediterranean Sea.ET-743 is planned to be registered and produced in Europe in 2002, and will be used to treat bone cancer, skin cancer, ovarian cancer, breast cancer and other common cancers.
India: The Indian government funded more than 50 research centers nationwide to collect human genome data.Due to the unique "caste system" and the internal intermarriage customs of some remote tribes, the gene bank of the Indian population is the most complete in the world, which 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.
JapanThe Japanese government has planned to increase the funds for biotechnology research by 23%.A private enterprise has also set up the "Dragon Gene Center", which will be the largest genome research institution in Asia.
SingaporeSingapore has announced a 60 million dollar genetic technology research project to study how diseases affect Asians and Caucasians differently.The plan focuses on the analysis of genetic differences and what treatment methods work for Asians, so as to finally obtain new knowledge for identifying and treating diseases;And set up high-tech companies to manufacture the drugs and medical products derived from this research institute.
China: Participated in the Human Genome Project and sequenced 1%, which has brought light to China's biological industry in the 21st century.This "1% project" has brought China into the international advanced ranks in the biological industry, and also made China naturally share all the achievements, resources and technologies of the Human Genome Project.
Obtaining the target gene is the first step of implementing genetic engineering.For example, plant disease resistance (anti-virus and anti-bacterial) genes, seed storage protein genes, and human insulin genesinterferonGenes are all target genes.
It is very difficult to obtain specific target genes from the vast "gene ocean".After unremitting exploration, scientists have come up with many methods, including two main ways: one is to directly separate genes from the DNA of donor cells;The other isSynthetic gene。
The most commonly used method for direct gene isolation is "shotgun method", also known as "shotgun method".Shotgun methodThe specific method is: cut the DNA in the donor cell into many segments with restriction enzyme, load these segments into the carrier respectively, and then transfer them into different recipient cells through the carrier, so that all segments of the DNA provided by the donor cell (i.e. foreign DNA) can be copied in large quantities in each recipient cell (ingeneticsIt is called amplification, such as using PCR technology). Find out the cells containing the target gene, and then use certain methods to separate the DNA fragments with the target gene.For example, many insect and virus resistant genes can be obtained by the above methods.
The advantage of obtaining the target gene by shotgun method is simple operation, but the disadvantage is heavy workload and blindness.Because the genes of eukaryotic cells contain DNA fragments that are not expressed, the method of artificial synthesis is generally used.
There are two main ways to synthesize genes.One way is to transcribe the target geneMessenger RNAIs a template,reverse transcriptionTo form complementary single stranded DNA, and then to synthesize double stranded DNA under the action of enzymes, so as to obtain the required genes.Another way is based on the known proteinamino acidSequence, infer the correspondingMessenger RNASequence, then followcomplementary base pairing The principle ofnucleotide sequence, and then through chemical methodsMononucleotideSynthesize target genes for raw materials.HumanoidhemoglobinGene insulin gene and so on can be obtained by the method of synthetic gene.
2. Combination of target gene and carrier
Gene expression vectorThe construction of the target gene (that is, the combination of the target gene and the carrier) is the second step of the implementation of genetic engineering, and is also the core of genetic engineering.
genetic engineering
The process of combining the target gene with the carrier is actually the process of recombination of DNA from different sources.If you useplasmidAs a carrier, first of all, the plasmid must be cut with a certain restriction enzyme to make a gap appear in the plasmid, exposing the sticky end.Then use the same restriction enzyme to cut off the target gene to produce the same sticky end (partRestriction endonucleaseThe flat end can be cut, with the same effect).Insert the cut segment of the target gene into the cut of the plasmid. First, the bases are complementary, paired and combined. The two sticky ends are anastomosed together to form a hydrogen bond between the bases. Then add an appropriate amountDNA ligase, catalyzing the formation between two DNA strandsPhosphodiester bondTo connect adjacent DNA to form a recombinant DNA molecule.For example, human insulin gene combines with plasmid DNA molecules in Escherichia coli in this way to form recombinant DNA molecules (also called recombinant plasmids).
threeTransfer the target gene into the receptor cell
The third step of genetic engineering is to introduce the target gene into the receptor cells.The next step is to introduce the recombinant DNA molecules into the receptor cells for amplification after the fragments of the target gene and the carrier are connected outside the body to form recombinant DNA molecules.
The receptor cells commonly used in genetic engineering are Escherichia coli,Bacillus subtilis, Agrobacterium tumefaciens,YeastHedongplant cellEtc.
Using artificial methods to transfer recombinant DNA molecules in vitro to recipient cells is mainly to learn from the way bacteria or viruses infect cells.For example, if the carrier is plasmid and the receptor cell is bacteria, the bacteria are generally treated with calcium chloride to increaseBacterial cell wallThe permeability of the recombinant plasmid containing the target gene into the receptor cell.After the target gene is introduced into the receptor cell, it can replicate with the reproduction of the receptor cell. Because of the rapid reproduction of bacteria, a large number of target genes can be obtained in a very short time.
4. Detection and expression of target gene
Whether the target gene can stably maintain and express its genetic characteristics after being introduced into receptor cells can only be known through detection and identification.This is the fourth step of genetic engineering.
After the above steps are completed, there are few receptor cells that can really take in recombinant DNA molecules.Therefore, it is necessary to detect whether the target gene is introduced into the receptor cells by certain means.There are many detection methods, for example, a certain plasmid of Escherichia coli haspenicillinResistance gene: when this plasmid is combined with foreign DNA to form a recombinant plasmid and transferred to the receptor cell, whether the receptor cell has obtained the target gene can be judged according to whether the receptor cell has penicillin resistance.After the recombinant DNA molecule enters the receptor cell, the receptor cell must show specificcharacterOnly in this way can the target gene complete the expression process.
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cloned sheep
The scientific community predicts that the 21st century will be a century of genetic engineering.Genetic engineering is an artificial intervention in biological genetics at the molecular level. To understand it, let's start with bioengineering: bioengineering, also known as biotechnology, is an applied modern sciencelife sciencesPrinciple and information and chemical technologyLiving cellOr its enzymes to process cheap raw materials to varying degrees, providing a large number of useful products of comprehensive engineering technology.
The foundation of bioengineering isModern life science, technical science and information science.The main product of bioengineering is to provide society with a large number of high-quality fermentation products, such as biochemical drugsChemical raw materials, energyBiological controlAs well as food and beverage, it can also provide human with environment treatment, metal extractionclinical diagnosis、gene therapyAnd improving crop varieties.
Biological engineering mainly includes five parts: genetic engineering, cell engineering, enzyme engineering, protein engineering and microbial engineering.Among them, genetic engineering is that people transform biological genesBiological productionSpecial products that people want.
Transgene chain
AmericanGilbertyesBaseThe founder of permutation analysis method, he took the lead in supporting the Human Genome Project. If a genetic code segment in the DNA of one organism is connected to the DNA chain of another organism, and the DNA is reorganized, wouldn't it be possible to design new genetic materials and create new biological types according to human wishes?This is totally different from the traditional practice of breeding biological offspring in the past. It is very similar to the engineering design of technology science, that is, according to the needs of human beings, this "gene" of this kind of organism and that "gene" of that kind of organism are re "constructed", "assembled" into a new gene combination, to create new organisms.This kind of biological science and technology, which is generated by reassembling genes to new organisms according to human wishes, is called "genetic engineering", or "genetic engineering".Human genome research is a basic research of life science.Some scientistsgenome map Seen as a road map, or in chemistryperiodic table of ele ments；Some scientists also compare the genome map to a dictionary, but no matter from which perspective to interpret, decipher the human gene code, so as to promote human health, prevent disease, and extend life, its application prospects are extremely bright.After the information of 100000 human genes and the corresponding chromosome positions have been deciphered, the genetic codes of humans, animals and plants have been deciphered, opening up a broad prospect for tackling diseases and improving crop yields.It will become the source of knowledge and technological innovation in the medical and biopharmaceutical industries.Beckowitz in the United States is observing thecolony of bacteriaHe once warned the Human Genome Project.
scientific researchIt is proved that some major diseases, such asCardiovascular and cerebrovascular diseases, diabetes, liver diseasecancerAll are related to genes.According to the deciphered gene sequence and function, these genes can be found and drugs can be screened for the corresponding lesion location, or even new drugs can be designed based on the existing gene knowledge, so that the genes of these lesions can be "targeted" to repair or replace, thus curing persistent diseases.gene drugsWill become the highlight of medicine in the 21st centuryStar。Gene research can not only provide basic data for screening and developing new drugs, but also make it possible to use genes to detect, prevent and treat diseases.For example, people with the same lifestyle and living environment have different susceptibility to the same disease due to different gene sequences.The obvious examples are that some people who are smokers are prone to lung cancer, while others are not.Doctors will give guidance to different people according to their different gene sequences, so that they can develop scientific and reasonable living habits and prevent diseases as much as possible.
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information technologyThe development of genetic engineering has changed the way of life of human beings, and the breakthrough of genetic engineering will help human beings prolong their lives.The average life expectancy of some countries has exceeded 80 years, and that of China has also exceeded 70 years.Some scientists predict that with thecancer、Cardiovascular and cerebrovascular diseasesWith the effective tackling of persistent diseases, countries with an average life expectancy of more than 100 years may emerge between 2020 and 2030.By 2050, human life expectancy will reach 90 to 95 years.
Found green fluorescent protein
Human beings will challenge the limits of life science.One day in February 1953, a British scientistFrancis Crick Announce: We have discovered the secret of life.He found that DNA is a kind ofdouble helixMolecules determine the heredity of living things.Interestingly, the scientistCambridgeThe important scientific discovery was announced in a bar of.Decipher human, animal and plantGene codeIt opens up a broad prospect for tackling diseases and improving crop yields.In 1987, American scientists proposed“human genome project”, the goal is to identify all human beingsgenetic information, determine the specific location of human genes on 23 pairs of chromosomes, and find out each genenucleotideTo establish human gene bank.In 1999, the genetic code of human chromosome 22 was deciphered“human genome project”A successful step has been taken.It can be predicted that in the next quarter century, scientists will probably reveal the pathogenic genes of about 5000 kinds of genetic diseases in human beings, so that cancerdiabetes、heart disease、hemophiliaWait for the fatal disease to be foundgene therapy 。
Following the announcement of the human genome by scientists on June 26, 2000“Work frame diagram"Later, scientists from six countries, including China, the United States, Japan, Germany, France and the United Kingdom, and Celera, the United States, jointly announced on February 12, 2001Human Genome MapAnd preliminary analysis results.The human genome map released this time is based on the original "work framework map", which has been collated, classified and arranged. It is more accurate, clear and complete.The human genome contains most of the genetic information of human life, aging, disease and death. Decoding it will bring a revolution to the diagnosis of diseases, the development of new drugs and the exploration of new therapies.The publication of the human genome map and preliminary analysis results willLife science and biotechnologyThe development of has played an important role in promoting.With the further development of human genome research,Life science and biotechnologyIt will enter a new era with the new century.
Genetic engineering has made great progress in the 20th century, which has at least two strong proofs.everythingTransgenic animals and plantsOne isCloning technology。Because transgenic animals and plants have implanted new genes, animals and plants have new traits that they did not have before, which caused aAgricultural revolution。Today,transgenic technologyIt has been widely used, such as insect resistant tomatoes, fast-growingCrucian carpEtc.The first of the world's top ten scientific and technological breakthroughs in 1997 was the birth of cloned sheep.This is called“Dolly”The ewe was the first to passAsexual reproductionThe resulting mammal completely inherits the genetic gene of the ewe that gave it the nucleus.“clone”It became the focus of attention for a while.Despite ethical and social concerns, the tremendous progress of biotechnology has given mankind a broader space to imagine the future.
In 1882, German embryologist WalterFlemingWhen studying salamander cells, we found that the nucleus contains a large number of mitotic linear objects, that is, later chromosomes;
1909DenmarkBotanists and geneticistsJohnsonThe term "gene" was first proposed to express Mendel's concept of genetic factor.
In 1944, three American scientists isolated bacterial DNA（Deoxyribonucleic acid）And discovered that DNA is a molecule that carries the genetic material of life.
In 1953, American biochemist Watson and British physicistCrickAnnounces that they have discovered the double helix structure of DNA, laying the foundation for genetic engineering;
In 1969, scientists successfully isolated the first gene.
In 1980, scientists first cultivated the world's firstTransgenic animaltransgenic mice。
In 1983, scientists first cultivated the world's firstTransgenic planttransgenic tobacco。
In 1985, the first batch of transgenic livestock (rabbits, pigs and sheep) was born.[3]
In October 1990, it was honored as life science“Apollo moon landing plan”OfInternational Human GenomePlan to start.
1994 Chinese Academy of SciencesZeng BangzhePut forward the plan of genetically modified poultry golden eggs and“Oviduct bioreactor(oviduct bioreactor) "and“Systematic genetics(system genetics) ".
In 1998, a group of scientists in the United StatesRockWill established Celera Genetics to compete with the International Human Genome Project.
December 1998NematodeThe determination of the complete genome sequence has been announced, which is the first time that scientists have mappedmulticellular The genome map of animals.
In September 1999, China was approved to join the Human Genome Project, 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, the United Kingdom, Japan, Germany and France, and the only developing country to participate in this project.
December 1, 1999Joint Research Group of the International Human Genome ProjectIt is announced that the genetic code of the 22nd pair of human chromosomes has been completely deciphered, which is the first time that humans have successfully completed the determination of the complete gene sequence of human chromosomes.
April 6, 2000CeleraAnnounce to decipher the integrity of an experimenterGenetic codeHowever, it was questioned by many scientists.
At the end of April 2000, according to the deployment of the International Human Genome Project, Chinese scientists completed 1%human genomeWork frame diagram of.
On May 8, 2000, scientists from Germany, Japan and other countries announced that they had basically completed the 21st pair of human bodieschromosomeThe sequencing work of.
On June 26, 2000, scientists released the working sketch of human genome, marking that human beings are interpreting themselves“Book of Life”An important step has been taken on our way.
On December 14, 2000, scientists from the United States, Britain and other countries announced thatArabidopsis thalianaA complete map of the genome, which is the first time that humans have fully decoded a plantGene sequence。
On February 12, 2001, scientists from China, the United States, Japan, Germany, France and the United Kingdom and Celera jointly released the human genome map and preliminary analysis results.
Scientists publish the first draft of the human genome“Genetic information”。
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Agriculture, animal husbandry and food industry
The application of genetic engineering technology can not only cultivate high-quality, high-yield, resistant crops and new varieties of livestock and poultry, but also cultivate animals and plants with special purposes.
1. Genetically modified fish
Genetically modified fish (China) with fast growth, tolerance to adverse environment and good meat quality.
Made of genetic engineeringDNA probeIt is very sensitive to detectViruses, bacteria, etc.
Indicator organisms cultivated by genetic engineering can reflect environmental pollution very sensitively, but they are not easy to die due to environmental pollution, and even can absorb and transform pollutants.
Made of genetic engineering“Superbacterium”It can ingest and decompose a variety of substances that pollute the environment (usually one bacterium can only decompose one hydrocarbon in the oil, and successfully cultivated by genetic engineering“Superbacterium”But can decompose various hydrocarbons in petroleumchemical compound。Some can swallow and transformmercury、cadmiumetc.heavy metal, decompositionDDTAnd other toxic substances.)
Genes asGenetic unitIt can not only determine our appearance and height, but also its abnormality will inevitably lead to the emergence of various diseases.someDefective geneIt may be passed on to offspring, while some cannot.Gene therapy was originally proposed for genetic diseases with single gene defects, aiming to have a normal gene to replace the defective gene or remedy the pathogenic factors of the defective gene.
Gene therapy is to introduce functional genes into the patient's body to make them express, and because the expression product - protein has played a role in making the disease treatable.The result of gene therapy is like an operation on genes to cure diseases and root causes, so some people describe it as“Molecular surgery”。
We can divide gene therapy into sex cell gene andSomatic gene therapyTwo types.Sex cell gene therapy is to operate in the sex cells of patients, so that their offspring will neverNoThis genetic disease.Somatic gene therapy is the mainstream of current gene therapy research.However, its shortcomings are also very obvious. It does not change the patients who have single or multiple gene defectsgenetic backgroundSo that some of his descendants will inevitably suffer from this disease.
No matter which kind of gene therapy is in the initial stage of clinical trials, it has no stable efficacy and complete safety, which is the current research status of gene therapy.
It can be said that without fully explaining the operating mechanism of the human genomegene regulation Mechanism and molecular mechanism of disease before gene therapy is quite dangerous.Enhance the safety of gene therapyClinical trialsThe strictness and rationality of are particularly important.Although there are still many obstacles to overcome in gene therapy, the general trend is encouraging.According to statistics, by the end of 1998, 373 clinical bills had been implemented worldwide and 3134 people had accepted themGene transferThe test fully shows its great development potential and application prospect.As the founders of gene therapy predicted at the beginning, the emergence of gene therapy will promote revolutionary changes in medicine in the new century.
Many drugs are produced frombiological tissue Extracted from.Due to the limitation of material sources, the output is limited, and the price is often very expensive.
microorganismRapid growth, easy to control, suitable for large-scale industrial production.If thebiosynthesisThe genes of corresponding drug ingredients are introduced into microbial cells to produce corresponding drugs, which can not only solve the production problem, but also greatly reduce the production cost.
⑴ Genetically engineered insulin
insulinIt's therapydiabetesFor a long time, we can only rely onpancreasThe 100Kg pancreas can only extract 4-5g insulin, and its low yield and high price can be imagined.
Introduction of synthetic insulin geneEscherichia coliEvery 2000L of culture medium can produce 100g insulin!Large scale industrial production not only solved the problem of drug production that is more expensive than gold, but also reduced its price by 30% - 50%!
⑵ Genetic engineering interferon
Interferon treatment of viral infection is“A panacea”！In the past, only 1mg of 300L blood was extracted from human blood!Its "precious" degree is needless to say.
Genetically engineered human interferonα-2b（Andafin）It is the first national production and chemical genetic engineering human interferon in Chinaα-2b, anti-virus, inhibitingtumourThe role of cell proliferation in regulating human immune function is widely used in the treatment of viral diseases and a variety of tumors. It is currently internationally recognized as the first choice for the treatment of viral diseasesTumor biotherapyThe main drug of.
Artificial bloodInterleukin、hepatitis B vaccineIndustrial production through genetic engineering has played an important role in relieving human suffering and improving human health.
2. Gene diagnosis and gene therapy:
Gene therapy is to introduce the normal gene into the patient's body, so that the expression product of the gene can play a role, so as to achieve the purpose of treating diseases, which is the most effective means of treating genetic diseases.The methods are: gene replacement, gene repair, gene addition and gene inactivation.
Designed and manufactured by genetic engineering“DNA probe”Detection of viral infection such as hepatitis virus andGenetic defect, not only accurate but also fast.Through genetic engineering, normal genes can be introduced into the human body suffering from genetic diseases to relieve the patients' suffering at one time.
However, the technology of gene therapy is not yet mature, and the key issues of the immature technology are: ① how to select effective therapeutic genes; ②How to construct a safe vector? The virus vector is highly efficient, but it has potential dangers; ③How to directionally introduce target cells and obtain high expression.
◆ SCID gene engineering treatment
Severe combined immunodeficiency(SCID) patients lack normal human immune function, as long as they are slightly infected by bacteria or viruses, they will get sick and die.The mechanism of this disease is an autosomalcodeAdenylate deaminase(ADA) gene (ada) has been mutated.It can be treated by genetic engineering.
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Since the mid-1980s, China's biotechnology has developed vigorously and achieved gratifying results.As the national high-tech research plan (i.e. the "863" plan), the key research plan and the National Natural Science Foundation all give priority support to biotechnology as a priority development field, the overall research level of biotechnology in China has rapidly improved, and a number of high-level research achievements have been achievedBiotechnology industryThe establishment and development of provides a technological source.ChinaGenetically engineered pharmaceuticalsThe industry has entered a period of rapid development.
Industry status
In 1989, China approved the first genetically engineered drug produced in China——Recombinant human interferonαLb, marking a breakthrough of zero for genetically engineered drugs produced in China.Recombinant human interferonαLb is the first Chinese in the worldGene cloningAnd expressed genetic engineering drugs, which is also the only independently developed and successfully owned by China so farIndependent intellectual property rightsA class of new drugs for genetic engineering.Since then, China's genetic engineering pharmaceutical industry has grown from scratch and continued to grow.In 1998, the sales volume of China's genetic engineering pharmaceutical industry reached 720 million yuan.By the end of 1998, the genetically engineered drugs andvaccineThere are 15 kinds of products in total.More than 30 domestic biopharmaceutical enterprises have obtained trial production or formal production of genetically engineered drugs or vaccinesApproval No。
According to the research results of 452 national biotechnology research, development and production units in 1997communicationAccording to the survey, by the end of 1996, eight kinds of genetically engineered drugs and vaccines had been commercialized (including trial production) in China. In 1996, the sales volume of genetically engineered drugs and vaccines was about 220 million yuan, accounting for only the same period in ChinaPharmaceutical BiologyThe annual sales volume of technical products is 2.116 billion yuan, 10.4% of the people.However, what is gratifying is that China's genetic engineering pharmaceutical industry has developed rapidly, with annual sales increasing from 220 million yuan in 1996 to 720 million yuan in 1998,Annual average growth rateUp to 80%.It is estimated that the sales volume of genetic engineering drugs in China will reach 2.28 billion yuan in 2000.
Genetic engineering has a broad development prospect in the pharmaceutical industry. China's genetic pharmaceutical industry has begun to take shape, but there is a gap with the developed countries in the world, which is mainly reflected in the small number of products with independent intellectual property rights, small industrial scale and low economic benefits.The gene pharmaceutical industry is facing historic opportunities, which are mainly manifested in government support, rich resources, and geneInformation disclosure, increased international exchanges, etc.It is urgent to improve the ability of independent development and protect genetic resources. At the same time, we should strengthen the research and preparation of technical barriers in the field of genetic medicine.
Comparison at home and abroad
The scale of China's biotechnology industry, especially the biopharmaceutical industry, lags far behind that of the United States.In 1996, the sales volume of biotechnology in China was 11.4 billion yuan, compared with 10 billion dollars in the United States, a difference of seven times.In 1996, the sales volume of genetic engineering and vaccines in China was 230 million yuan, compared with US $7.5 billion in the same period.In 1998, the sales volume of genetic engineering drugs and vaccines in China was 720 million yuan, less than 100 million dollars. In 1996, the two main products of American Amgen, Neupgen (G-CSF) and Epogen（Erythropoietin）Sales reached US $1 billion.
In 1998, 15 kinds of genetically engineered drugs and vaccines were approved for marketing in China and those in the United StatesBiopharmaceuticalsThere are 53 kinds of drugs (mainly genetic engineering drugs).The market time of Chinese base engineering drugs is 5 to 10 years later than that of the same varieties in the United States.
Main problems
1. There are too many manufacturers of the same kind of products, causing vicious competition in the market and seriously affecting the healthy development of the industry:
The vast majority of genetically engineered drugs and vaccines approved for marketing in China are produced by multiple manufacturers.For example: interferonα2a There are 5 manufacturers of interferonα2b There are 5,Interleukin-2There are 10, 7 for G-CSF and 6 for GM-CSF.The clinical dosage of genetic engineering drugs is generally very small (microgram level), and usually 2-3 manufacturers can meet the needs of the national market with full capacity.Therefore, too many manufacturers producing the same kind of genetically engineered drugs will inevitably lead to excessive market competition, which will reduce the profits of each production enterprise. At the same time, it will also lead to insufficient starting of existing production capacity and increased costs, which will make enterprises unable to obtain reasonable profits and enter the track of healthy development, and even force some enterprises to suffer serious losses and bankruptcy.
This phenomenon of repeated production has something to do with the guiding ideology of new drug research and development in China.In the past, the research and development of new drugs in China was mainly based on the introduction and development. Most of the new drugs developed, listed and under development in China were copied from abroad, and there were few innovative drugs.Among the 15 approved genetic engineering drugs and vaccines, only interferonαLb owns my own intellectual property rights.Among the new biological drugs studied, the vast majority were tracked and developed in China after foreign countries entered Phase II and Phase III clinical trials.It is easy to see that the lack of innovation and low-level duplication in China's new drug research and development is the source of repeated production in the pharmaceutical industry.Strengthening the research of innovative drugs is the fundamental way to solve the problem of repeated production of genetic engineering drugs from the source.At the same time, China must further improve the new drug approval system and patent system, encourage innovation from the system, effectively protect the intellectual property rights of innovators, and avoid repeated production.
2. Single financing channel and insufficient funds for industrial development:
Genetically engineered pharmaceutical industry is a typical technology industry with the characteristics of high investment, high risk and high income.Most Chinese genetic engineering pharmaceutical enterprises invest 20 million yuan to 100 million yuan.In addition to the equity capital invested by shareholders, the source of funds is mainly bank loans, and the financing channel is narrow.As banks pay great attention to the security and liquidity of funds, the risks of high-tech investment make banks cautious about lending.At the same time, China's genetic engineering medicine makes theseEnterprise financing capacityObviously insufficient, it is difficult to obtain funds needed for enterprise development from general financing channels.The serious shortage of development funds has become a huge obstacle to the development of genetic engineering pharmaceutical industry.Therefore, China should learn from the successful experience of foreign countries in using venture capital to develop high-tech industries, formulate relevant laws and policies, and actively and steadily start venture capital.
3. The competition in the pharmaceutical market is out of order, and the unhealthy tendencies in the industry are prevalent:
With China's transition from a planned economy to a market economy, new changes have taken place in the pharmaceutical market, and the profit distribution in all aspects of drug purchase and sale is extremely unreasonable.According to the current national price regulations, the wholesale price of drugs is 115% of the factory price and the retail price is 120% of the wholesale price.However, in the actual marketing of genetic engineering drugs, hospitals generally purchase drugs at 70% - 85% of the national wholesale price, thus obtaining a profit of 30% - 50% of the retail price, while the profit of manufacturers is only 5% - 15%.This unreasonable distribution of profits has led to losses in many pharmaceutical enterprises.More importantly, the same genetic engineering drugs are produced by multiple manufacturers, forcing manufacturers to adopt high pricing and high margin promotion methods, which further worsens the competition in the drug market.Under the pressure of the market, enterprises are mainly focused on market competition, unable to take into account technological innovation.Too much market investment and profit concession make normal production and operation very difficult, let alone how to develop.The vicious competition in the pharmaceutical market has not only failed toconsumerBenefited, but the interests of the country, pharmaceutical enterprises and consumers have been greatly damaged.
In addition, according to the survey, the sales prices of most imported genetic engineering drugs are much higher than those of domestic drugs of the same kind. What's more unreasonable is that more than half of the imported genetic engineering drugs are sold at higher prices in China than in the country of origin.
4. Enterprise management is relatively backward, and there is a shortage of technical and operational talents:
China's genetic engineering pharmaceutical industry started late, but the starting point is relatively high.The key production equipment of many enterprises is imported from abroad.However, there is still a big gap between China and foreign countries in terms of operation and management.modern enterprise system One of its characteristics is the separation of ownership and management. The owners of enterprises supervise the operators, and the operators make theValue maintenance and appreciation of assets。Most genetic engineering pharmaceutical enterprises in China are limited liability companies or joint-stock companies in form, but all operators of the enterprises are generally assumed or appointed by the enterprises.The fact that the ownership and management of an enterprise are indistinguishable is not conducive to the long-term development of the enterprise, nor is it conducive to the formation of the enterprise management class, that is, the entrepreneur class.
Genetic engineering pharmaceutical enterprises are typical technology intensive high-tech enterprises. In order to survive and develop in the fierce competition, enterprises must have a group of high-quality compound talents.How to train and bring up a group of such talents has become an urgent problem for China's biopharmaceutics.
Countermeasures and policy suggestions
According to the current situation and development trend of engineering pharmaceutical industry at home and abroad, in order to promote the rapid and healthy development of China's genetic engineering pharmaceutical industry, we propose the following suggestions:
The blindness and serious duplication of China's genetic engineering pharmaceutical industry are related to the lack of clear industrial development strategies and plans.Therefore, China should formulate and issue the development strategy and guiding development plan of biotechnology industry as soon as possible, concentrate its limited financial and material resources on the introduction, digestion, absorption, innovation and transformation of traditional industries, and focus on supporting a number of enterprises with independent intellectual property rights and international competitive advantages,Key genetic engineering industrialization projects that have a significant impact on national economic development and people's life.Only in this way can China's genetic engineering pharmaceutical industry avoid blindness and anarchy and embark on the road of sound development.
Like other high-tech industries, genetic engineering pharmaceutical industry has the characteristics of high input, high risk and high output. At the initial stage, it must rely on the support of national preferential policies to continue to grow.Although the Chinese governments at all levels have formulated many preferential policies to support the development of high-tech industries, the intensity of preferential policies is not enough, and there are many departments involved in the specific implementation process, which often fail to implement.Therefore, it is recommended that the state further strengthen and standardize the financialPreferential tax policies。
2. Vigorously strengthen the development and production of genetically engineered innovative drugs
Since the vast majority of genetic engineering drugs on the market and under research in China are copied from abroad, it is difficult for Chinese genetic engineering drugs to enter the international market.Especially after China's accession to the WTO, some genetic engineering pharmaceutical enterprises will be in a very passive position and may face patent disputes.In order to fundamentally change the situation of repeated production and lack of international competitiveness of China's genetic engineering pharmaceutical industry, China's new drug development and development ideas must be strategically adjusted from focusing on imitation to combining innovation and imitation.To this end, China must vigorously strengthen the research of innovative drugs, further improve the intellectual property protection system and the new drug approval system, in particular, strengthen the fight against intellectual property infringement, and effectively protect the rights and interests of innovators.At the same time, new drug development units and individuals should pay attention to learning to use patents to protect their own interests.The strategy of "patent plus publication" adopted by some foreign companies is instructive.In order to patent their own technology and prevent others from applying for the same patent, American companies quickly publish the patent content after applying for a patent.This practice not only established its own leading position, but also effectively prevented others from applying for the same patent.
At the same time of strengthening the research of innovative drugs, we can selectively legally imitate some patents that are about to expire, with clear curative effects and broad application prospects.The patents related to generic drugs should be carefully studied, and effective patent avoidance strategies should be adopted to avoid simple and blind generic drugs.We should innovate on the basis of imitation.Create different production processes and methods of patented methods to avoid patent disputes.
3. Actively guide and cultivate the venture capital market
Financing difficulties and insufficient funds have seriously restricted the rapid development of China's genetic engineering pharmaceutical industry.The successful experience of European and American developed countries shows that venture capital is an effective way to solve the financial difficulties in the process of high-tech commercialization and industrialization.Therefore, the Chinese government should actively and steadily guide and foster venture capital, make laws and policies for the operation of venture capital, create a relaxed environment and conditions for venture capital, and allow investment banksTrust and Investment Company, insurance companies and other institutionsVenture capital fund。Actively attract the inflow of foreign venture capital funds.At the same time, high-tech enterprises should also be relaxedConditions for issuance of sharesAnd provide more opportunities for high-tech enterprises to go public.Actively prepare to open up the second stock market for high-tech enterprises, creating conditions for venture capital to enter and exit the capital market.
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aboutTransgenic organismThere is no scientific consensus on the safety of.Nevertheless, genetically engineered crops have been launched on a large scale,biomedical scienceApplications are also increasing.Genetically modified organisms are also used in industry andEnvironmental recoveryHowever, the public knows little about it.In recent years, more and more evidence has proved that there are ecological and health hazards and risks, which also have adverse effects on farmers.
Genetically engineered bacteria affect soil organisms and cause plant death.
The research materials published in 1999 exemplify how the release of genetically engineered microorganisms into the environment will lead to widespread ecological destruction.
When the genetically engineered strains of Klebsiella, sand and wheat crops are added into the microcosm, the bacteria andfungusThe number increased significantly, leading to plant death.When parental non genetic engineering strains were added, only the number of bacteria feeding nematode organisms increased, and plants would not die.The introduction of any strain into soil without plants would not change nematode communities.
Klebsiella is a common bacteria that can ferment lactoseSoil bacterium。Genetically engineered bacteria are manufactured to produce enhanced ethanol concentrates in fermentation drums that convert agricultural waste into ethanol.Fermentation residues, including genetically engineered bacteria, can also beSoil improvement。
Research proves that someSoil ecosystemThe genetically engineered bacteria in can survive for a long time under certain conditions, and the time is long enough to stimulateSoil organismChanges will occur, affecting plant growth and nutrient cycle process.Although the extent of such in-situ observation is still unclear, the discovery of plant death caused by genetically engineered bacteria also shows that it is possible to kill crops if such soil improvement is used.
Australian researchers accidentally created a killer virus that can completely destroy mice when developing genetic engineering for relatively harmless mouse pox virus.
The researchers willwhite blood cellThe gene of interleukin 4 (naturally produced in the body) is inserted into a mouse pox virus to promote the production of antibodies and create a mouse pregnancy avoidance vaccine for controlling mouse damage.Surprisingly, the inserted gene completely inhibited theimmune system。The mouse pox virus usually causes only mild symptoms, but after adding the IL-4 gene, the virus will kill all animals within 9 days.To make matters worse, this genetically engineered virus has extraordinary resistance to vaccination.
Although the improved mouse pox virus has no impact on humans, it is closely related to smallpox, which makes people worry that genetic engineering will be used in biological warfare.A researcher once said when talking about the reasons why they decided to publish the research results: "We want to warn the ordinary people that there is such potentially dangerous technology now", "We also want to let the scientific community understand that we must act carefully, and it is not too difficult to create high-risk and deadly organisms."
InsecticideThe increase in use is largely due to the increased use of pesticides in HT crops, especially HT soybeans, which can be traced back to the heavy dependence on HT crops and the use of a single herbicide (glyphosate) for weed management.This has led to the transfer to more difficult to control weeds, and genetic resistance has also emerged in some weeds, forcing many farmers to spray more herbicides on genetically engineered crops to properly control weeds.The glyphosate resistant marine algae in HT soybeans first appeared in the United States in 2000, and it has also been identified in HT cotton [27].
Other studies have shown that genetically engineered crops themselves will also be resistant to the herbicides they use, causing serious self growing crop problems (plants sprouting from crop seeds planted earlier in the same field later become weeds) and forcing further use of herbicides.CanadaScientists have confirmed the rapid evolution of genetically engineered rape resistant to multiple herbicidespollenLong distance transmission combines the characteristics of monovalent herbicide resistance developed by different companies.
In addition, scientists also confirmed in 2002 that transgenic plants can move from Bt sunflowers to nearby wild sunflowers, making hybrids stronger and more resistant to chemicals, because compared with the situation without gene control, hybrids have 50% more seeds, and the seeds are healthy, even under drought conditions.
The research of North Carolina State University shows that the cross between Bt rape and related weeds, bird feeding grass can produce insect resistant hybrids, making weed control more difficult.
All these events make the prevention method and strictBio-SafetyManagement becomes prominent.The precautionary principle has been reaffirmed in the Cartagena Biosafety Agreement, the international law governing genetically modified microorganisms.In particular, Article 10 (6) states that, in the absence of scientific conclusions, Parties may restrict or prohibit the import of genetically modified organisms to avoid or minimize adverse effects on biodiversity and human health.
