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Detailed History of Discoveries & Advancements Related to Plant Improvement 1838 Schwann and Schleiden outlined the theory of totipotency: the capacity of a single cell regenerate a complete organism. 1865 Gregor Medel establishes laws of heredity: (1) segregation and (2) independent assortment (although not deduced until 1900 and 1913) 1869 Johann Friedrich Miescher identifies a weakly acidic substance of unknown function in the nuclei of human white blood cells. This substance will later be called deoxyribonucleic acid, or DNA. 1900 Rediscovery of Mendel’s work by Tschermark, deVries and Correns (independently), which deduced Mendel’s 1st Law of Heredity: Units of inheritance must separate (segregation). 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 – 1908 William Bateson and Reginald Crudell Punnett, along with others, demonstrated that some genes modify the action of other genes. 1907 Thomas Hunt Morgan began his work with fruit flies that will prove that chromosomes have a definite function in heredity, establish mutation theory, and lead to a fundamental understanding of the mechanisms of heredity, including independent assortment in 1913 (Mendels Law 2). 1909 British physician Archibald Garrod first proposes the relationship between genes and proteins. He hypothesizes that genes might be involved in creating the proteins that carry out the chemical reactions of metabolism. 1909 Phoebus Levene discovered that the sugar ribose is found in some nucleic acids, those we now call RNA 1910 Thomas Hunt Morgan proved that genes are carried on chromosomes, establishing the basis of modern genetics. With his co-workers, he pinpointed the location of various fruit fly genes on chromosomes, establishing the use of Drosophila fruit flies to study heredity. Morgan's group also demonstrated the existence of sexlinked genes, and over the next ten years expanded the idea to other trait linkages, using "crossing-over" to help determine the location of genes, establishing a methodology for creating the first genetic map and deduction of Mendel’s second law: Independent Assortment. 1912 Physicist Sir William Henry Bragg, and his son, Sir William Lawrence Bragg, discover that they can deduce the atomic structure of crystals from their X-ray diffraction patterns. This scientific tool will be key in helping Watson and Crick determine DNA's structure. 1913 Alfred H. Sturtevant, a student of Morgan's, 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 thus calculated the exact percentage of crossing-over between the genes 1917 Plough demonstrated the rearrangement of chromosomes known as crossing over 1917 F. D'Herelle described "an invisible microbe" that antagonizes the bacillus that causes dysentery and coined the term "bacteriophage" for the antagonist. Phage caused plaques on bacterial lawns, analogous to colonies on agar plates. Later plaques will prove useful in preparing pure cultures and characterizing different strains of the bacteriophages or bacterial viruses 1920s Plant hybridization became widespread in the United States, greatly improving the productivity of agriculture 1924 Microscope studies using stains for DNA and protein show that both substances are present in chromosomes. 1925 Nikolai Vavilov led Russian plant hunters on the first attempt to "cover the globe" in search of wild plants and primitive cultivators. For his scientific curiosity, he was later thrown in prison, dying there of malnutrition in 1943 1926 Thomas Hunt 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 1926 Hermann Muller discovered that X-rays induce genetic mutations in fruit flies 1,500 times more quickly than under normal circumstances. This discovery provided researchers with a way to induce mutations, an important tool for discovering what genes do on their own 1926 Henry Agard Wallace, US Secretary of Agriculture during the Franklin Roosevelt's first two terms, and Vice-president during his third, founded the Hi-Bred Company - a hybrid corn seed producer and marketer known today as Pioneer Hi-Bred International, Inc. 1928 Fredrick Griffiths noticed that a rough type of bacterium changed to a smooth type when an unknown "transforming principle" from the smooth type was present. Sixteen years later, Oswald Avery identified that "transforming principle" as DNA. 1928 Lewis Stadler showed that ultraviolet radiation can also cause mutations 1929 Phoebus Levene discovered a previously unknown sugar, deoxyribose, in nucleic acids that do not contain ribose; those nucleic acids are now known as deoxyribonucleic acids, or DNA. 1933 T.S. Painter announced in a brief article in Science that he had charted perceptible differences among chromosomes under the microscope - differences detailed enough to correlate crossing-over of genes as shown in the statistical tables with physical interchanges in the material of the chromosomes 1934 Martin Schlesinger purified bacteriophage and found about equal amounts of protein and DNA. Which of these was the informational molecule remained unclear 1935 Andrei Nikolaevitch Belozersky isolated DNA in the pure state for the first time 1936 Wendell M. Stanley isolated nucleic acids from the tobacco mosaic virus, which later (1955) will be found to cause the viral activity 1937 Frederick Charles Bawden discovered that tobacco mosaic virus contains RNA 1938 The term "molecular biology" was coined 1939 Gauteret cultivated carrot callus cultures 1941 George Beadle and Edward Tatum experimented with Neurospora, a mold that grows on bread in the tropics, developing the "one-gene-one-enzyme" hypothesis: each gene is translated into an enzyme to perform tasks within an organism. They examined X-ray-damaged mold specimens that would not grow on the sample medium, but would grow if they added a certain vitamin. They hypothesized that the X-rays had damaged the genes that synthesized the proteins. 1943 The Rockefeller Foundation, collaborating with the Mexican government, initiated the Mexican Agricultural Program. This was the first use of plant breeding as foreign aid. 1944 Oswald Theodore Avery, Colin MacLeod and Maclyn McCarty determined that DNA is the hereditary material involved in transformation in pneumococcus bacteria. At first this theory gained little attention because scientists believed that DNA was too simple a molecule to contain all of the genetic information for an organism. Most scientists believed that only proteins were complex enough to express all of the genetic combinations. 1946 Edward Tatum and Joshua Lederberg showed that bacteria sometimes exchange genetic material directly, in a process they called conjugation. 1946 D.C. Salmon, a U.S. military adviser stationed in Japan, sent home Norin 10 - the source of the dwarfing gene that later helped produce the Green Revolution wheat varieties. 1946 Max Delbruck and Alfred Day Hershey independently discovered that the genetic material from different viruses can be combined to form a new type of virus. This process was another example of genetic recombination. 1947 Barbara McClintock first reported on "transposable elements" - known today as "jumping genes." The scientific community failed to appreciate the significance of her discovery at the time. 1950 Erwin Chargaff found that in DNA the amounts of adenine and thymine are about the same, as are the amounts of guanine and cytosine. These relationships are later known as "Chargaff's Rules" and serve as a key principle for Watson and Crick in assessing various models for the structure of DNA. 1953 James Watson and Francis Crick discover the molecular structure of DNA. 1953 William Hayes discovered that plasmids can be used to transfer introduced genetic markers from one bacterium to another. 1957 During a dysentery epidemic in Japan, biologists discover that some strains of bacterium are resistant to antibiotics. Later scientists will find that this resistance is transferred by plasmids. 1957 Francis Crick and George Gamov worked out the "central dogma," explaining how DNA functions to make protein. Their "sequence hypothesis" posited that the DNA sequence specifies the amino acid sequence in a protein. They also suggested that genetic information flows only in one direction, from DNA to messenger RNA to protein, the central concept of the central dogma 1957 Mexico became self-sufficient in wheat production for the first time as a result of plant breeding efforts that began in 1943 1957 Matthew Meselson and Frank Stahl demonstrated the replication mechanism of DNA 1958 Coenberg discovered and isolated DNA polymerase, which became the first enzyme used to make DNA in a test tube 1958 The National Seed Storage Laboratory (NSSI) was opened in Fort Collins, Colorado, becoming the first long-term seed storage facility in the world 1959 Reinart regenerated plants from carrot callus culture 1959 Francois Jacob and Jacques Monod established the existence of genetic regulation mappable control functions located on the chromosome in the DNA sequence which they named the repressor and operon. They also demonstrated the existence of proteins that have dual specificities 1959 Nikita Krushchev introduced hybrid corn to the Soviet Union after visiting an Iowa corn farm belonging to Roswell Garst 1961 Sidney Brenner and Francis Crick establish that groups of three nucleotide bases, or codons, are used to specify individual amino acids. 1962 Francis Crick, James Watson, and Maurice Wilkins receive the Nobel Prize for determining the molecular structure of DNA. 1962 The planting of high-yield wheat varieties (later known as Green Revolution grains) began in Mexico. The seeds were released by the Mexican Agricultural Program to other countries 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 is deciphered when biochemical analysis reveals which codons determine which amino acids. 1967 The enzyme DNA ligase was isolated. DNA ligase binds together strands of DNA. Its discovery, with the isolation of the first restriction enzyme 1970, paved the way for the first recombinant DNA molecules to be created by Paul Berg in 1972. In the recombinant DNA process, ligase bonds the "sticky" ends of complimentary DNA strands previously cut by a restriction enzyme. 1969 James Shapiero of Harvard University, working with Johnathan Beckwith announce that they had isolated the first gene. The gene directed the digestion of sugar in a certain type of bacteria. Shapiero and Beckwith's discovery part of a wave of molecular biology discoveries directly following the 1966 cracking of the genetic code. The announcement also increased the public's concern about the growing power of molecular biologists. 1970 The first restriction enzyme is isolated (Reverse Transcriptase). Credit is given to Howard Temin, David Baltimore and/or Hamilton Smith (depending on source) as being the first to accomplish this task. 1972 Paul Berg of Stanford University created the first recombinant DNA molecules by combining the DNA of two different organisms. 1972 The first successful DNA cloning experiments were performed in California 1973 Stanley Cohen and Herbert Boyer created the first recombinant DNA organism using recombinant DNA techniques pioneered a year earlier by Paul Berg. Recombinant DNA, also called gene splicing, is a technique that allows scientists to manipulate the DNA of an organism. This technology will be the beginning of the biotechnology industry. 1973 Bruce Ames, a biochemist at UC Berkeley, developed a test to identify chemicals that damage DNA. The Ames Test becomes a widely used method to identify carcinogenic substances 1974 Cohen and Boyer showed that DNA can be cut with restriction enzymes and reproduced by inserting the recombinant DNA into Escherichia coli 1975 The Asilomar Conference. A moratorium on recombinant DNA experiments was called for at an international meeting at Asilomar, California, where scientists urged the government to adopt guidelines regulating recombinant DNA experimentation. The scientists insisted on the development of "safe" bacteria and plasmids that could not escape from the laboratory 1976 Herbert Boyer cofounds Genentech, the first firm founded in the United States to apply recombinant DNA technology 1976 The NIH released the first guidelines for recombinant DNA experimentation. The guidelines restricted many categories of experiments 1978 Somatostatin, which regulates human growth hormones, is the first human protein made using recombinant technology. 1978 RFLPs are discovered by David Botstein and others. When a restrictive enzyme is applied to DNA from different individuals, the resulting sets of fragments sometimes differ markedly from one individual to the next. 1980 The U.S. Supreme Court ruled in that genetically altered life forms can be patented. A Supreme Court decision in 1980 allowed the Exxon oil company to patent an oileating microorganism. This ruling opened up enormous possibilities for commercially exploiting genetic engineering. 1980 Kary Mullis and others at Cetus Corporation in Berkeley, California, invented a technique for multiplying DNA sequences in vitro by, the polymerase chain reaction (PCR). PCR has been called the most revolutionary new technique in molecular biology in the 1980s. Cetus patented the process, and in the summer of 1991 sold the patent to Hoffman-La Roche, Inc. for $300 million. 1982 The FDA approves the first genetically engineered drug, a form of human insulin produced by bacteria to Genentech. 1982 Lindow requested government permission to test genetically engineered bacteria to control frost damage to potatoes and strawberries. 1983 The first U.S. patents were granted to several companies for genetically engineering plants 1984 Charles Cantor and David Schwartz developed pulsed-field gel electrophoresis 1984 Alec Jeffreys introduces technique for DNA fingerprinting to identify individuals 1986 Caltech and Applied Biosystems, Inc., invented the automated DNA fluorescence sequencer 1986 The FDA granted a license for the first recombinant vaccine (for hepatitis) to Chiron Corp 1986 The EPA approved the release of the first genetically engineered crop, gene-altered tobacco plants 1987 Calgene, Inc. received a patent for the tomato polygalacturonase DNA sequence, used to produce an antisense RNA sequence that can extend the shelf-life of fruit 1987 Advanced Genetic Sciences, Inc. conducted a field trial of a recombinant organism, a frost inhibitor, on a Contra Costa County strawberry patch 1987 Maynard Olson and colleagues at Washington University invented "yeast artificial chromosomes," or YACs, expression vectors for large proteins 1988 China grows genetically engineered tobacco commercially until the mid-1990’s. 1990 The first successful field trial of genetically engineered cotton plants was conducted by Calgene Inc. The plants had been engineered to withstand use of the herbicide Bromoxynil 1990 Michael Fromm, molecular biologist at the Plant Gene Expression Center, reported the stable transformation of corn using a high-speed gene gun 1990 The Human Genome Project was launched. Estimated cost: $13 billion. 1990 Chymosin produced by genetically engineered bacteria approved in US for commercial uses 1992 FDA issues policy statement that genetically engineered foods would not be regulated any differently than conventional foods 1993 Kary Mullis won the Nobel Prize in Chemistry for inventing the technology of polymerase chain reaction 1993 The Biotechnology Industry Organization is created by merging two smaller trade associations 1994 The first genetically engineered food is introduced in US – Flavr-Savr tomatoes, by Calgene 1995 The second genetically engineered food is introduced in US – Virus resistant squash, by Asgrow 1995 Endless Summer tomato test marketed by DNAP, but never fully commercialized because it lost a lawsuit with Monsanto over the technology 1995 Genetically engineered tomato paste marketed in the UK by Zeneca (same technology as Flavr-Savr). Crop grown in California and product sold in the UK 1995 BXN Cotton (resistant to the herbicide bromoxynil (Rhone-Poulenc's Buctril)) commercialized by Calgene 1995 High laurate rapeseed commercialized by Calgene 1995 The first full gene sequence of a living organism other than a virus is completed for the bacterium Hemophilus influenzae 1995 Sequence Tag Site Mapping technique developed by James Sikela for high-speed mapping in the international Human Genome Project 1996 Roundup Ready Soybeans commercialized by Monsanto 1996 Bt Corn commercialized by Ciba-Geigy 1996 Bollguard and Roundup Ready Cotton commercialized by Monsanto 1996 DNA sequence of the complete genome of the first complex organism (Saccharomyces cerevisiae) is determined. 1997 Flavr-Savr Tomatoes no longer available 1997 Male sterile raddichio deregulated by US, but withdrawn by Bejo Zaden in 1999 prior to commercialization 1998 Virus Resistant Papaya grown commercially in Hawaii beginning in May 1998 Herbicide tolerant sugar beets deregulated by US, but never commercialized 1998 The first complete animal genome (C.elegans) is sequenced 1998 Herbicide tolerant flax cleared by Canadian regulators, but never commercialized 2000 Herbicide tolerant rice deregulated by FDA (and previously by USDA in 1999), but EPA has not approved the new use of the herbicide 2000 Genetically engineered tomato paste no longer sold in UK 2001 China issues new regulations for genetically engineered products that require mandatory labeling and safety assessment. 2002 Estimates of GE crops grown in the US: Soybean – 74%, Cotton – 71%, corn – 31%