History Of Animal Biotechnology Ppt
2 2 Animal biotechnology range from in vitro culture of animal cell, tissue and organs to transgenic animal production. Molecular biology is an indispensable part of the transgenic animal production.
3 3 1907: Ross Harrison: made the first attempt to culture animal cells and cultivated embryonic nerve cells of a frog by using hanging drop method. 1912: Alexis Carrel: used tissue and embryo extract as culture media. After using the mixture of chick embryo and plasma, cell proliferation was enhanced in vitro. The fibrin clot of plasma served as an anchor for cell attachment and the extract provided growth factors and nutrients. 1919: First use of the word ‘BIOTECHNOLOGY” in print.
4 4 1928: Alexander Fleming discovered Penicillin 1940s: antibiotic discovery improves culture method as contamination could be controlled. Thus large culture venture started. 1940s: many human carcinoma cell lines (e.g. HeLa cell line) were isolated and grown in culture. Alex Carrel: under in vitro condition kept chick embryo heart alive and its beating continued in vitro for about three months. (this is the first successful organ culture) 1940s: Recombination of virus to give rise to new viruses proved. 1940s: Total stop of using monkey for multiplication of animal viruses.
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5 5 Late 1940s: Enders, Welter and Robbins: grew poliomyelitis virus in culture. They provided an momentum to give an easy way to test many chemical and antibiotics that affect multiplication of virus in living host cells. 1. Virus can be grown in animal tissue culture 2. Chemical toxicity analysis which effect virus multiplication in living host cells. 3. Vaccine production 1954: cell culturing techniques started 1965: Harris and Watkins successfully fuse mouse and human cells.
6 6 1966: Alec Issac: infected the culture cells with virus and collected filtrate from the infected cells. Again he cultured fresh cells in medium containing filtrate. Such cells were not infected when challenged with viruses. He predicted that the virus-infected cells secreted molecules which coated the surface of fresh cells (uninfected cells). These molecules interfered the entry of viral particles in the uninfected cells. Issac called these molecules as interferon. Issac was called MAD.
7 7 Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens, such as, viruses, bacteria, parasites or tumor cells. Interferons are named after their ability to interfere with viral replication within host cells. They allow for communication between cells to trigger the protective defenses of the immune system to eradicate pathogens or tumors. IFNs have other functions: a) they activate immune cells, b) they increase recognition of infection or tumor cells by T lymphocytes; and c) they increase the ability of uninfected host cells to resist new infection by virus.. About ten distinct IFNs have been identified in mammals; seven of these have been described for humans. They are typically divided among three IFN classes: Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all IFN classes are very important for fighting viral infections.
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8 8 1975: first monoclonal antibodies are produced using recombinant technology 1980: with recombinant DNA technology the interferon gene was cloned and expressed in bacterial cells. The biological function of interferon that Issac claimed was proved. Now interferon α, β and γ are one of the most successful biotech product in the market.
9 9 Erythopoitine: In 1905, Paul Carnot, a professor of medicine in Paris, and his assistant, Clotilde Deflandre, proposed the idea that hormones regulate the production of red blood cells. After conducting experiments on rabbits Carnot and Deflandre attributed an increase in red blood cells in rabbit subjects to a hemotropic factor called hemopoietin. Eva Bonsdorff and Eeva Jalavisto continued to study red cell production and later called the hemopoietic substance 'erythropoietin'. Further studies confirmed that the EPO existed in the body circulate in the blood and stimulate red blood cell production. This substance was finally purified and confirmed as erythropoietin, opening doors to therapeutic uses for EPO in diseases such as anemia. In 1968, Goldwasser and Kung began work to purify human EPO, and managed to purify milligram quantities of over 95% pure material by 1977. Pure EPO allowed the amino acid sequence to be partially identified and the gene to be isolated. Later, an NIH-funded researcher at Columbia University discovered a way to synthesize EPO. Columbia University patented the technique, and licensed it to Amgen.
10 10 In 1985, human erythropoietin gene was characterize and produced through recombinant technology. Their research demonstrated the gene for erythropoietin encoded the production of EPO in mammalian cells that is biologically active in vitro and in vivo. Soon after clinical trial was done for Epogen, produced by Amgen. The trial was successful. In 1989, the US Food and Drug Administration approved the hormone Epogen, which remains in use today. 1980s: Recombinant erythropoietin was produced on Chinese Hamster Ovary (CHO) cell lines by AMGEN (USA). Within ten year AMGEN become the first billion biotech company only due to erythropoietin production in CHO cell line.
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11 11 1996: Wilmut and co-workers: Successfully produced a transgenic sheep named Dolly through nuclear transfer technique. Dolly was cloned by transferring nucleus of a mammary (udder) cell into enucleated ovum of an adult sheep. Now many animal e.g. sheep, goat, pigs, fishes, bird etc. were produced. 2002: Human genome society of France: claimed to produce a cloned human baby named Eve.
12 12 Applications of Animal Biotechnology Production of enzyme ( brewing, food processing, textile & leather industries) Production of vaccines Monoclonal antibody Pharmaceutical drugs Diagnostics kits Cancer research Improvement of live stock Transgenic animal research etc.
13 13 BST Story For successful commercialization of recombinant product there are few things that we need to consider 1.Basic science for identification and characterization of the product 2.Production through rDNA tech. 3.Technology transfer to get the process to a commercially viable stage 4.Approval by the regulatory bodies 5.Market acceptance and establishment of consumer base rBST/ rBGH: Recombinant bovine somatotropin/ Recombinant bovine growth hormone
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14 14 BST: bovine growth hormone naturally occurring peptide hormone produced by pituitary gland, acts as a growth promoter in cattle, milk production increase by administrating BST Thus it was an attractive target for cloning and production for use in the dairy industry.
15 15 The basic science for rBST: Somatotropin was discovered in 1936 by a team of Soviet researchers, who then tried to reproduce it to stimulate milk production in livestock, but the technology of the time did not allow them to produce an artificial hormone. At the end of the 1970s, Monsanto’s researchers succeeded in isolating the responsible gene. Through genetic manipulation, they introduced the gene into Escherichia coli, thus facilitating its large scale production. The product then known as “Recombinant Bovine Somatotropin” (rBST), or “recombinant Bovine Growth Hormone”. (rBGH). From the start of the 1980s, Monsanto organize trials on its own experimental farms or in collaboration with universities, like, Vermont and Cornell. Injections of the hormone twice a month allowed milk yield to be increased by at least 15%, equivalent to on average a gallon, or 3.8 litres a day. The hormone rBST was launched on the market under the brand name Posilac by Monsanto in 1994, with the Food and Drug Administration (FDA) approval.
16 16 Public acceptance: 1. Need: EU didn’t approve the product due to Socioeconomic reasons (increasing milk production was not needed at that time) 2. Consumers concerns: a. effect on milk production b. effect on cow c. effect on consumer
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17 17 a.Effect on milk production Milk production increase by 10-15% in treated cows. Thus from dairy management view point, use of rBST would be beneficial. b. Effect on cow Administrating rBST can produce localized swelling at the site of injection. Counter agreement: many of these problems occur anyway, even in herbs that are rBST-free.
18 18 c. Effect on consumers: BST and administered rBST increase milk production by increasing the level of “insulin like growth factor (IGF-1), which causes increase in milk production. IGF-1 can stimulate the growth of cancer cell. Thus, the concern is that using rBST could pose a risk to health. Counter agreement: the level of IGF-1 in the early stage of lactation are higher than those generated by the use of rBST in cows 100 days after lactation begins, which is often when it is administered. This means that milk from early lactating cows should not be drunk at all if there are any concern about IGF-1.
19 19 Opposing the counter agreement: unlike a therapeutic protein that would be used for a limited number of patients, milk would be consumed by most people. And any inherent risk, no matter how small, is therefore unacceptable. On the basis of this uncertainty, many countries have banned the use of rBST, citing both animal health issue and the potential risk to health as reasons. Q. Animal Biotechnology may rise “Billion Biotech Company”-state your views with example.
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20 20 Business of Biotech Product: patent, price and safety: Anemia drugs built Amgen into the world’s biggest biotechnology company. It has been one of the most lucrative monopolies of all time, yielding Amgen, a biotechnology company
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