A Portal on Biotechnology

Timetable: The Development of Genetic Engineering

31.01.1999 · Research Group on the Global Future

1724	Cross fertilization in corn was discovered
1856	Karl Ludwig discovered a technique for keeping animal organs alive outside the body, by pumping blood through them.
1859	Charles Darwin hypothesized that animal populations adapt their forms over time to best exploit the environment, a process based on "natural selection". He reasoned that only the creatures best suited to their environment survive to reproduce.
1863	Anton de Bary proved that fungus causes potato blight. A Challenge for scientists during this period was to discern whether a microbe was the cause or the result of a disease.
1864	Louis Pasteur argued that decayed organisms are found as small-organized "corpuscles" or "germs" in the air.
1866	Gregor Mendel was the first person to trace the characteristics of successive generations of living beings. He found that the plants' respective offspring retained the essential traits of the parents, and therefore were not influenced by the environment. This simple test gave birth to the idea of heredity.
1869	Johann Miescher discovered DNA, although he just tried to identify the chemicals in cells.
1870	Walter Flemming discovered mitosis.
1871	DNA was isolated from the sperm of trout in the Rhine River.
1873-76	Robert Koch investigated anthrax and developed techniques to view, grow and stain organisms.
1875	Charles Darwin proposed the idea of "gemmules" as a mechanism of inheritance.
1882	Walter Flemming reported his discovery of chromosomes and mitosis.
1883	August Weismann coined the term "germ-plasma." He asserted that male and female parents contribute equally to the heredity of the offspring and that chromosomes must be the bearers of heredity.
1887	Edouard van Beneden discovered that each species has a fixed number of chromosomes; he also discovered the formation of haploid cells during cell division of sperm and ova.
1902	Walter Sutton stated that chromosomes are paired and may be the carriers of heredity. Archibald Garrod made the connection between Mendelian heredity and the biochemical pathways of reproduction in the individual organism.
1903	Walter Sutton and Theodor Boveri proposed that each egg or sperm cell contain only one of each chromosome pairs.
1904	William Bateson demonstrated that some characteristics are not independently inherited. This introduced the concept now called "gene linkage" and led to the need for "genetic maps" that describe the order of the linked genes.
1905	Edmund Wilson proposed the idea that separate X and Y chromosomes determine sex. He showed that a single Y chromosome determines maleness and the two X chromosomes determine femaleness.
1905-08	William Bateson and Reginald Punnett demonstrated that some genes modify the action of other genes.
1907	Thomas Morgan proved that chromosomes have a definite function in heredity. He established mutation theory and lead the way to a fundamental understanding of the mechanism of heredity.
1908	Archibald Garrod described "inborn errors of metabolism" based on his analysis of family medical history. This was the first recognition of a role for genetics in biochemistry.
1913	Alfred Sturtevant constructed the first gene map by analyzing mating results for fruit flies with six different mutant factors each known to be recessive and X-linked. He traced each mutation and its normal alternate in relation to each of the other mutants, and calculated the exact percentage of crossing-over between the genes.
1917	Thomas Morgan demonstrated the rearrangement of chromosomes known as "crossing over".
1918	Henry Evans found that human cells contain 48 chromosomes.
1926	Thomas Morgan published "The theory of the gene"; the culmination of work on the physical basis for Mendelian genetics based on breeding studies and optical microscopy.
1933	Thomas Painter announced that he had charted perceptible differences among chromosomes under the microscope - differences detailed enough to correlate crossing-over of genes.
1934	Hermann Schlesinger purified bacteriophage and found about equal amounts of protein and DNA
1935	Anton Belozersky isolated DNA in the pure state for the first time.
1938	Proteins and DNA were studied in various labs with X-ray crystallography. The term "molecular biology" was coined.
1943	Salvador Luria and Max Delbrück performed the "fluctuation test", the first study of mutation in bacteria. This was the beginning of bacterial genetics as a distinct discipline.
1944	DNA was determined to be the hereditary material involved in the transformation of pneumococcus bacteria.
1945	The UN Food and Agriculture Organization (FAO) was formed in Quebec, Canada.
1950	Erwin Chargaff found that the amounts of adenine and thymine are about the same in DNA, as are the amounts of guanine and cytosine. These relationships have later been known as "Chargaff´s Rules."
1953	James D. Watson and Francis Crick proposed the double-stranded, helial, complementary, anti-parallel model of the DNA-Structure. In 1962 they were rewarded with the Nobel Prize for Physiology and Medicine.
1955	Francis Crick and George Gamov worked out the "central dogma", explaining how DNA functions to make protein. They also suggested that genetic information flows only in one direction, from DNA messenger RNA to protein, the central concept of the central dogma.
1957	Mathew Meselon and Franklin Stahl demonstrated the replication mechanism of DNA.
1959	Francois Jacob and Jaques Monod established the existence of genetic regulation, which they named the repressor and operon. They also demonstrated the existence of proteins that have dual specificity.
1965	Scientists noticed that genes conveying antibiotic resistance in bacteria are often carried on small, supernumerary chromosomes called plasmids. This observation led to the classification of the plasmids.
1966	The genetic code was cracked. Marshall Warren Nirenberg and Severo Ochoa demonstrated that a sequence of three nucleotide bases (a codon) determines each of 20 amino acids.
1967	Arthur Kornberg conducted a study using one strand of natural viral DNA to assemble 53000 nucleotide building blocks.
1970	Howard Temin and David Baltimore isolated "reverse transcriptase" a restriction enzyme that cuts DNA molecules at specific sites. This discovery allowed scientists to create clones and observe their function.
1972	Paul Berg isolated and employed a restriction enzyme to cut DNA. He used ligase to paste two DNA strands together to form a hybrid circular molecule. This was the first recombinant DNA molecule. The first successful DNA cloning experiments were performed in California.
1973	Stanley Cohen and Paul Boyer "spliced" sections of viral DNA and bacterial DNA with the same restriction enzyme, creating a plasmid with dual antibiotic resistance, thereby producing the first recombinant DN" organism.
1975	Conference of Asilomar (CA) Scientists urged the government to adopt guidelines regulating recombinant DNA experimentation, because of the potential risk of Gentechnology. César Milstein and Georges Köhler fused cells together to produce monoclonal antibodies.
1976	Foundation of Genentech Inc, one of the largest US biotechnological companies.
1977	The US National Institute of Health (NIH) released the first guidelines for recombinant DNA experimentation. Since then all projects concerning the NIH have to be registered and published.
1978	Harvard researchers used genetic engineering techniques to produce rat insulin.
1979	James Baxter reported cloning the gene for the human growth hormone.
1980	The Supreme Court of the US ruled that genetically altered life forms can be patented. This ruling opened up enormous possibilities for the commercial exploitation of genetic engineering. Kary Mullis (UCB) invented a technique for multiplying DNA sequences in vitro through the polymerase chain reaction (PCR).
1981	Scientists at Ohio University produced the first transgenic animals by transferring genes from other animals into mice.
1982	The US Food and Drug Administration approves the first genetically engineered drug, a form of human insulin produced by bacteria. Joseph Goldstein, a later Nobel Prize Winner for Physiology and Medicine in 1985, called for the prohibition of the use of RNA technologies in the development of biological weapons.
1983	US patents were granted to companies genetically engineering plants.
1984	Alec Jeffreys introduced techniques for DNA fingerprinting to identify individuals.
1985	Genetic fingerprinting enters the court room. Cal Bio cloned the gene that encodes human lung surfactant protein, a major step toward reducing a premature birth complication.
1986	Development of the so-called Polymerase Chain-Reaction, a technique used to make numerous copies of a specific segment of DNA quickly and accurately. The polymerase chain reaction enables investigators to obtain large quantities of DNA which are required for various experiments and procedures in molecular biology.
1987	Researchers at the Washington University invented "yeast artificial chromosomes" (YACs) expression vectors for large proteins.
1988	Harvard molecular geneticists were awarded the first patent of a genetically altered animal, a mouse which is highly susceptible to breast cancer.
1989	The European Patent Office refuse a genetically altered mouse.
1990	The first gene therapy takes place on a four-year old girl with an immune system disorder called ADA (Adenosin Desaminase) deficiency, a lack of leukocytes. The therapy appeared to work, but set off a fury of discussion of ethics both in academia and in the media.
1991	Scientist from the University of California, Berkeley, analyzed chromosomes from women in cancer-prone families, and found out that a gene on chromosome 17 causes the inherited form of breast cancer and also increases the risk of ovarian cancer.
1992	The European Patent Office starts a new procedure about the use of genetically altered beings.
1993	The US Food and Drug administration (FDA) declares that genetically engineered foods are "not inherently dangerous" and do not require special regulations. However, they have to be labeled. July, Convention on Biological Diversity 165 countries signed the Convention and 31 nations ratified the Convention, which is based on a broad ecosystem approach and contains three national-level obligations: to conserve and sustainably use biological diversity, and to share its benefits. Today there are 172 member states.
1994	The first genetically engineered food product for commercial use, the Flavr Savr tomato, gained FDA approval in the USA. Genetic researchers successfully transferred the CFTR (cystic fibrosis transmembrane conductance regulator) gene into the intestines of mice. This appears to be a major step towards gene therapy for patients with cystic fibrosis. Researchers reported early success with a liposomal method for delivering the CFTR gene in humans.
1995	Researchers at Duke Medical University transplanted hearts from genetically altered pigs into baboons, proving that cross-species operations are possible. A new mapping technique, STS gene mapping, greatly accelerated the work of geneticists involved in the international Human Genome Project. Gene therapy, immune system modulation and genetically engineered antibodies enter the clinic in the war against cancer.
1996	In the EU it is allowed to cultivate genetically modified corn (Novartis) and soybeans (Monsanto).
1997	Researchers at Scotland´s Roslin Institute report that they have cloned a sheep - named Dolly - from the cell of an adult ewe. Thereafter Polly, the first sheep cloned by nuclear transfer technology bearing a human gene, appears. The European Union (EU) adopted its Novel Foods Regulation (258/97/EC) on January 27th . The Regulation has been under consideration for the past several years. It establishes a process for the evaluation of novel foods and novel food ingredients (e.g., fat substitutes). These are foods and food ingredients that have not previously been used for human consumption to a significant degree in the EU, or foods and food ingredients obtained by a new production process which changes their properties. A new DNA technique combining PCR, DNA chips and computer programming provides a new tool in the search for disease-causing genes. The new patent guideline of the EU passed.
1998	A rough draft of the human genome map has been produced, showing the locations of more than 30 000 genes. In the EU, genetically modified corn (Novartis) and soybeans (Monsanto) have to be labeled since June. (Regulation on the release of genetically modified organisms). In four countries of the EU (France, Great Britain, Switzerland and the Netherlands) genetically modified food has to be labeled since September.
1999	Greenpeace reports in January that more and more Companies start to label their genetically modified food. A new technique based on unique individual antibody allow quick identification of BSE/CJD, a rare but devastating form of neurologic disease transmitted from cattle to humans. EU Moratorium on new releases of genetic modified plants. The EU ministers of the environment decided in July to implement a new regulation on the release of GMOs. The new regulation is going to be expected in 2002. Until then, a factual ban on any new approvals for commercial release of GMO goes on. At December 14th the European Patent Office gives the University of Edinburgh the patent No. EP 695 351 erroneously. It also includes the manipulation of human germ-cells
2000	Celera Genomics announced on January 10th that the company has DNA sequence in the Celera database that covers 90 percent of the human genome. Celera is now on target to complete the sequencing phase of the human genome by summer 2000. According to the new regulation on the release of GMOs, modified corn and soybeans have to be labeled at a threshold value of 1% in the EU. Genetically modified additives and flavors also have to be labeled from 10th April 2000. The new law is going to be enacted in April. Global treaty on GMOs: After five years of talks, ministers and senior officials from over 130 governments have finalized the Biosafety Protocol (see: www.biodiv.org) on January 29th . This is a legally binding agreement for protecting the environment from risks posed by the transboundary transport of living modified organisms (LMOs) created by modern biotechnology. Minimal Genome project TIGR: The focus of this project is a bacterium called Mycoplasma genitalium. A research team found out that this organism is able to get by with a mere 470 genes. By contrast, humans are reckoned to have 80,000 to 100,000 genes. Human Genome Project: President Clinton and Prime Minister Blair announced on March 14th that the human genome and DNA sequence data should be made available to the public. It will promote discoveries that will reduce the burden of diseases. Intellectual Property Protection for gene-based inventions will also play an important role for the development of important new health care products. Celera Genomics´s chief scientist Craig Venter announced on April 6th that they completed the gene sequence plan of one human being, A breakthrough that opens the door to precise understanding of what causes diseases of all kinds.