Cronologia della biotecnologia 8000 B.C. Humans domesticate crops and livestock. Potatoes first cultivated for food. 4000 — 2000 B.C. Biotechnology first used to leaven bread and ferment beer, using yeast (Egypt). Production of cheese and fermentation of wine (Sumeria, China and Egypt). Babylonians control date palm breeding by selectively pollinating female trees with pollen from certain male trees. 500 B.C. First antibiotic: moldy soybean curds used to treat boils (China). A.D. 100 First insecticide: powdered chrysanthemums (China). 1322 An Arab chieftain first uses artificial insemination to produce superior horses. 1590 Janssen invents the microscope. 1663 Hooke discovers existence of the cell. 1675 Leeuwenhoek discovers bacteria. 1761 Koelreuter reports successful crossbreeding of crop plants in different species. 1797 Jenner inoculates a child with a viral vaccine to protect him from smallpox. 1830 – 1833 1830 — Proteins discovered. 1833 — First enzyme discovered and isolated. 1835 – 1855 Schleiden and Schwann propose that all organisms are composed of cells, and Virchow declares, "Every cell arises from a cell." 1857 Pasteur proposes microbes cause fermentation. 1859 Charles Darwin publishes the theory of evolution by natural selection. The concept of carefully selecting parents and culling the variable progeny greatly influences plant and animal breeders in the late 1800s despite their ignorance of genetics. 1865 Science of genetics begins: Austrian monk Gregor Mendel studies garden peas and discovers that genetic traits are passed from parents to offspring in a predictable way — the laws of heredity. 1870 – 1890 Using Darwin's theory, plant breeders crossbreed cotton, developing hundreds of varieties with superior qualities. Farmers first inoculate fields with nitrogen-fixing bacteria to improve yields. William James Beal produces first experimental corn hybrid in the laboratory. 1877 — A technique for staining and identifying bacteria is developed by Koch. 1878 — The first centrifuge is developed by Laval. 1879 — Fleming discovers chromatin, the rod-like structures inside the cell nucleus that later came to be called chromosomes. 1900 Drosophila (fruit flies) used in early studies of genes. 1902 The term immunology first appears. 1906 The term genetics is introduced. 1911 The first cancer-causing virus is discovered by Rous. 1914 Bacteria are used to treat sewage for the first time in Manchester, England. 1915 Phages, or bacterial viruses, are discovered. 1919 First use of the word biotechnology in print. 1920 The human growth hormone is discovered by Evans and Long. 1928 Penicillin discovered as an antibiotic: Alexander Fleming. A small-scale test of formulated Bacillus thuringiensis (Bt) for corn borer control begins in Europe. Commercial production of this biopesticide begins in France in 1938. Karpechenko crosses radishes and cabbages, creating fertile offspring between plants in different genera. Laibach first uses embryo rescue to obtain hybrids from wide crosses in crop plants — known today as hybridization. 1930 U.S. Congress passes the Plant Patent Act, enabling the products of plant breeding to be patented. 1933 Hybrid corn, developed by Henry Wallace in the 1920s, is commercialized. Growing hybrid corn eliminates the option of saving seeds. The remarkable yields outweigh the increased costs of annual seed purchases, and by 1945, hybrid corn accounts for 78 percent of U.S.-grown corn. 1938 The term molecular biology is coined. 1941 The term genetic engineering is first used by Danish microbiologist A. Jost in a lecture on reproduction in yeast at the technical institute in Lwow, Poland. 1942 The electron microscope is used to identify and characterize a bacteriophage — a virus that infects bacteria. Penicillin mass-produced in microbes. 1944 DNA is proven to carry genetic information — Avery et al. Waksman isolates streptomycin, an effective antibiotic for tuberculosis. 1946 Discovery that genetic material from different viruses can be combined to form a new type of virus, an example of genetic recombination. Recognizing the threat posed by loss of genetic diversity, the U.S. Congress provides funds for systematic and extensive plant collection, preservation and introduction. 1947 McClintock discovers transposable elements, or "jumping genes," in corn. 1949 Pauling shows that sickle cell anemia is a "molecular disease" resulting from a mutation in the protein molecule hemoglobin. 1951 Artificial insemination of livestock using frozen semen is successfully accomplished. 1953 The scientific journal Nature publishes James Watson and Francis Crick's manuscript describing the double helical structure of DNA, which marks the beginning of the modern era of genetics. 1955 An enzyme involved in the synthesis of a nucleic acid is isolated for the first time. 1956 Kornberg discovers the enzyme DNA polymerase I, leading to an understanding of how DNA is replicated. 1958 Sickle cell anemia is shown to occur due to a change of a single amino acid. DNA is made in a test tube for the first time. 1959 Systemic fungicides are developed. The steps in protein biosynthesis are delineated. Also in the 1950s Discovery of interferons. First synthetic antibiotic. 1960 Exploiting base pairing, hybrid DNA-RNA molecules are created. Messenger RNA is discovered. 1961 USDA registers first biopesticide: Bacillus thuringiensis, or Bt. 1963 New wheat varieties developed by Norman Borlaug increase yields by 70 percent. 1964 The International Rice Research Institute in the Philippines starts the Green Revolution with new strains of rice that double the yield of previous strains if given sufficient fertilizer. 1965 Harris and Watkins successfully fuse mouse and human cells. 1966 The genetic code is cracked, demonstrating that a sequence of three nucleotide bases (a codon) determines each of 20 amino acids. (Two more amino acids have since been discovered.) 1967 The first automatic protein sequencer is perfected. 1969 An enzyme is synthesized in vitro for the first time. 1970 Norman Borlaug receives the Nobel Peace Prize (see 1963). Discovery of restriction enzymes that cut and splice genetic material, opening the way for gene cloning. 1971 First complete synthesis of a gene. 1972 The DNA composition of humans is discovered to be 99 percent similar to that of chimpanzees and gorillas. Initial work with embryo transfer. 1973 Stanley Cohen and Herbert Boyer perfect techniques to cut and paste DNA (using restriction enzymes and ligases) and reproduce the new DNA in bacteria. 1974 The National Institutes of Health forms a Recombinant DNA Advisory Committee to oversee recombinant genetic research. 1975 Government first urged to develop guidelines for regulating experiments in recombinant DNA: Asilomar Conference, California. The first monoclonal antibodies are produced. 1976 The tools of recombinant DNA are first applied to a human inherited disorder. Molecular hybridization is used for the prenatal diagnosis of alpha thalassemia. Yeast genes are expressed in E. coli bacteria. The sequence of base pairs for a specific gene is determined (A, C, T, G). First guidelines for recombinant DNA experiments released: National Institutes of Health-Recombinant DNA Advisory Committee. 1977 First expression of human gene in bacteria. Procedures developed for rapidly sequencing long sections of DNA using electrophoresis. 1978 High-level structure of virus first identified. Recombinant human insulin first produced. North Carolina scientists show it is possible to introduce specific mutations at specific sites in a DNA molecule. 1979 Human growth hormone first synthesized. Also in the 1970s First commercial company founded to develop genetically engineered products. Discovery of polymerases. Techniques for rapid sequencing of nucleotides perfected. Gene targeting. RNA splicing. 1980 The U.S. Supreme Court, in the landmark case Diamond v. Chakrabarty, approves the principle of patenting recombinant life forms, which allows the Exxon oil company to patent an oil-eating microorganism. The U.S. patent for gene cloning is awarded to Cohen and Boyer. The first gene-synthesizing machines are developed. Researchers successfully introduce a human gene — one that codes for the protein interferon — into a bacterium. Nobel Prize in Chemistry awarded for creation of the first recombinant molecule: Berg, Gilbert, Sanger. 1981 Scientists at Ohio University produce the first transgenic animals by transferring genes from other animals into mice. Chinese scientist becomes the first to clone a fish — a golden carp. 1982 Applied Biosystems, Inc., introduces the first commercial gas phase protein sequencer, dramatically reducing the amount of protein sample needed for sequencing. First recombinant DNA vaccine for livestock developed. First biotech drug approved by FDA: human insulin produced in genetically modified bacteria. First genetic transformation of a plant cell: petunia. 1983 The polymerase chain reaction (PCR) technique is conceived. PCR, which uses heat and enzymes to make unlimited copies of genes and gene fragments, later becomes a major tool in biotech research and product development worldwide. The first genetic transformation of plant cells by TI plasmids is performed. The first artificial chromosome is synthesized. The first genetic markers for specific inherited diseases are found. First whole plant grown from biotechnology: petunia. First proof that modified plants pass their new traits to offspring: petunia. 1984 The DNA fingerprinting technique is developed. The entire genome of the human immunodeficiency virus is cloned and sequenced. 1985 Genetic markers found for kidney disease and cystic fibrosis. Genetic fingerprinting entered as evidence in a courtroom. Transgenic plants resistant to insects, viruses and bacteria are field-tested for the first time. The NIH approves guidelines for performing gene-therapy experiments in humans. 1986 First recombinant vaccine for humans: hepatitis B. First anti-cancer drug produced through biotech: interferon. The U.S. government publishes the Coordinated Framework for Regulation of Biotechnology, establishing more stringent regulations for rDNA organisms than for those produced with traditional genetic modification techniques. A University of California Berkeley chemist describes how to combine antibodies and enzymes (abzymes) to create pharmaceuticals. The first field tests of transgenic plants (tobacco) are conducted. The Environmental Protection Agency approves the release of the first transgenic crop — gene-altered tobacco plants. The Organization of Economic Cooperation and Development (OECD) Group of National Experts on Safety in Biotechnology states: "Genetic changes from rDNA techniques will often have inherently greater predictability compared to traditional techniques" and "risks associated with rDNA organisms may be assessed in generally the same way as those associated with non-rDNA organisms." 1987 First approval for field test of modified food plants: virus-resistant tomatoes. Frostban, a genetically altered bacterium that inhibits frost formation on crop plants, is field-tested on strawberry and potato plants in California, the first authorized outdoor tests of a recombinant bacterium. 1988 Harvard molecular geneticists are awarded the first U.S. patent for a genetically altered animal — a transgenic mouse. A patent for a process to make bleach-resistant protease enzymes to use in detergents is awarded. Congress funds the Human Genome Project, a massive effort to map and sequence the human genetic code as well as the genomes of other species. 1989 First approval for field test of modified cotton: insect-protected (Bt) cotton. Plant Genome Project begins. Also in the 1980s Studies of DNA used to determine evolutionary history. Recombinant DNA animal vaccine approved for use in Europe. Use of microbes in oil spill cleanup: bioremediation technology. Ribozymes and retinoblastomas identified. 1990 Chy-Max™, an artificially produced form of the chymosin enzyme for cheese-making, is introduced. It is the first product of recombinant DNA technology in the U.S. food supply. The Human Genome Project — an international effort to map all the genes in the human body — is launched. The first experimental gene therapy treatment is performed successfully on a 4-year-old girl suffering from an immune disorder. The first transgenic dairy cow — used to produce human milk proteins for infant formula — is created. First insect-protected corn: Bt corn. First food product of biotechnology approved in U.K.: modified yeast. First field test of a genetically modified vertebrate: trout. 1992 American and British scientists unveil a technique for testing embryos in vitro for genetic abnormalities such as cystic fibrosis and hemophilia. The FDA declares that transgenic foods are "not inherently dangerous" and do not require special regulation. 1993 Merging two smaller trade associations creates the Biotechnology Industry Organization (BIO). FDA approves bovine somatotropin (BST) for increased milk production in dairy cows. 1994 First FDA approval for a whole food produced through biotechnology: FLAVRSAVR™ tomato. The first breast cancer gene is discovered. Approval of recombinant version of human DNase, which breaks down protein accumulation in the lungs of CF patients. BST commercialized as POSILAC bovine somatotropin. 1995 The first baboon-to-human bone marrow transplant is performed on an AIDS patient. The first full gene sequence of a living organism other than a virus is completed, for the bacterium Hemophilus influenzae. Gene therapy, immune system modulation and recombinantly produced antibodies enter the clinic in the war against cancer. 1996 The discovery of a gene associated with Parkinson's disease provides an important new avenue of research into the cause and potential treatment of the debilitating neurological ailment. 1997 First animal cloned from an adult cell: a sheep named Dolly in Scotland. First weed- and insect-resistant biotech crops commercialized: Roundup Ready® soybeans and Bollgard® insect-protected cotton. Biotech crops grown commercially on nearly 5 million acres worldwide: Argentina, Australia, Canada, China, Mexico and the United States. A group of Oregon researchers claims to have cloned two Rhesus monkeys. 1998 University of Hawaii scientists clone three generations of mice from nuclei of adult ovarian cumulus cells. Human embryonic stem cell lines are established. Scientists at Japan's Kinki University clone eight identical calves using cells taken from a single adult cow. The first complete animal genome, for the C. elegans worm, is sequenced. A rough draft of the human genome map is produced, showing the locations of more than 30,000 genes. Five Southeast Asian countries form a consortium to develop disease-resistant papayas. Also in the 1990s First conviction using genetic fingerprinting in the U.K. Discovery that hereditary colon cancer is caused by defective DNA repair gene. Recombinant rabies vaccine tested in raccoons. Biotechnology-based biopesticide approved for sale in the United States. Patents issued for mice with specific transplanted genes. First European patent on a transgenic animal issued for transgenic mouse sensitive to carcinogens. 2000 First complete map of a plant genome developed: Arabidopsis thaliana. Biotech crops grown on 108.9 million acres in 13 countries. "Golden Rice" announcement allows the technology to be available to developing countries in hopes of improving the health of undernourished people and preventing some forms of blindness. First biotech crop field-tested in Kenya: virus-resistant sweet potato. Rough draft of the human genome sequence is announced. 2001 First complete map of the genome of a food plant completed: rice. Chinese National Hybrid researchers report developing a "super rice" that could produce double the yield of normal rice. Complete DNA sequencing of the agriculturally important bacteria, Sinorhizobium meliloti, a nitrogen-fixing species, and Agrobacterium tumefaciens, a plant pest. A single gene from Arabidopsis inserted into tomato plants to create the first crop able to grow in salty water and soil. 2002 The first draft of a functional map of the yeast proteome, an entire network of protein complexes and their interactions, is completed. A map of the yeast genome was published in 1996. International consortia sequence the genomes of the parasite that causes malaria and the species of mosquito that transmits the parasite. The draft version of the complete map of the human genome is published, and the first part of the Human Genome Project comes to an end ahead of schedule and under budget. Scientists make great progress in elucidating the factors that control the differentiation of stem cells, identifying over 200 genes that are involved in the process. Biotech crops grown on 145 million acres in 16 countries, a 12 percent increase in acreage grown in 2001. More than one-quarter (27 percent) of the global acreage was grown in nine developing countries. Researchers announce successful results for a vaccine against cervical cancer, the first demonstration of a preventative vaccine for a type of cancer. Scientists complete the draft sequence of the most important pathogen of rice, a fungus that destroys enough rice to feed 60 million people annually. By combining an understanding of the genomes of the fungus and rice, scientists will elucidate the molecular basis of the interactions between the plant and pathogen. Scientists are forced to rethink their view of RNA when they discover how important small pieces of RNA are in controlling many cell functions.