Sharda bt ppt

What is biotechnology? • Biotechnology = bios (life) + logos (study of or essence)

– Literally ‘the study of tools from living things’

• CLASSIC: The word "biotechnology" was first used in 1917 to describe processes using living organisms to make a product or run a process, such as industrial fermentations. (robert Bud, The Uses of Life: A History of Biotechnology)

• LAYMAN: Biotechnology began when humans began to plant their own crops, domesticate animals, ferment juice into wine, make cheese, and leaven bread (Acess Excellence)

http://www.accessexcellence.org/AB/BC/what_is_biotechnology.html

What is biotechnology? • GENENTECH: Biotechnology is the process of

harnessing 'nature's own' biochemical tools to make possible new products and processes and provide solutions to society's ills (G. Kirk Raab, Former President and CEO of Genentech)

• WEBSTER’S: The aspect of technology concerned with the application of living organisms to meet the needs and ends of man.

• WALL STREET: Biotechnology is the application of genetic engineering and DNA technology to produce therapeutic and medical diagnostic products and processes. Biotech companies have one thing in common - the use of genetic engineering and manipulation of organisms at a molecular level.

What is biotechnology?

• Using scientific methods with organisms to produce new products or new forms of organisms

• Any technique that uses living organisms or substances from those organisms or substances from those organisms to make or modify a product, to improve plants or animals, or to develop microorganisms for specific uses

What is biotechnology?

• Biotechnology is a multidisciplinarian in nature, involving input from

• Engineering• Computer Science• Cell and Molecular Biology• Microbiology• Genetics• Physiology• Biochemistry• Immunology• Virology• Recombinant DNA Technology Genetic manipulation

of bacteria, viruses, fungi, plants and animals, often for the development of specific products

History of Biotechnology

• The term “biotecnology" was coined in 1919 by Karl Ereky, an Hungarian engineer

• Traditional biotechnology has been used for thousands of years to produce improved food and health care products. Today, modern biotechnology enables us to develop improved products more safely and more rapidly than ever before.

• Biotechnology in one form or another has flourished since prehistoric times.

What are the stages of biotechnology?

• Ancient Biotechnology• early history as related to food and shelter,

including domestication

• Classical Biotechnology• built on ancient biotechnology• fermentation promoted food production• medicine

• Modern Biotechnology• manipulates genetic information in organism• genetic engineering

• Long history of fermented foods since people began to settle (9000 BC) (fervere –to boil)

• Often discovered by accident!

• Improved flavor and texture

• Deliberate contamination with bacteria or fungi (molds)

• Examples:•Bread•Yogurt•Sour cream•Cheese•Wine•Beer•Sauerkraut

Ancient biotechnology

Fermented foods and beverages

• Dough not baked immediately would undergo spontaneous fermentation would rise Eureka!!

• Uncooked fermented dough could be used to ferment a new batch no longer reliant on “chance fermentation”

• 1866 – Louis Pasteur published his findings on the direct link between yeast and sugars CO2 + ethanol (anaerobic process)

• 1915 – Production of baker’s yeast – Saccharomyces cerevisiae

Ancient biotechnology

Fermented foods and beverages

•Different types of beer•Vinegar•Glycerol•Acetone•Butanol•Lactic acid•Citric acid•Antibiotics – WWII (Bioreactor developed for large scale production, e.g. penicilin made by fermentation of penicillium)

•Today many different antibiotics are produced by microorganisms•Cephalosporins, bacitracin, neomycin, tetracycline……..)

Classical biotechnology

Industry today exploits early discoveries of the fermentation process for production of huge numbers of products

• Substrate + Microbial Enzyme Product

• Examples:• Cholesterol Steroids (cortisone, estrogen, progesterone) (hydroxylation reaction -OH group added to cholesterol ring)


Chemical transformations to produce therapeutic products

• Amino acids to improve food taste, quality or preservation

• Enzymes (cellulase, collagenase, diastase, glucose isomerase, invertase, lipase, pectinase, protease)

• Vitamins

• Pigments


Microbial synthesis of other commercially valuable products

• Cell biology• Structure, organization and reproduction

• Biochemistry• Synthesis of organic compounds• Cell extracts for fermentation (enzymes versus whole cells)

• Genetics• Resurrection of Gregor Mendel’s findings 1866 1900s

• Theory of Inheritance (ratios dependent on traits of parents)• Theory of Transmission factors

• W.H. Sutton – 1902• Chromosomes = inheritance factors

• T.H. Morgan – Drosophila melanogaster

Modern biotechnology

Molecular Biology

• Beadle and Tatum (Neurospora crassa)• One gene, one enzyme hypothesis

• Charles Yanofsky colinearity between mutations in genes and amino

acid sequence (E. coli)• Genes determine structure of proteins

• Hershey and Chase – 1952 • T2 bacteriophage – 32P DNA, not 35S protein

is the material that encodes genetic information


• Watson, Crick, Franklin and Wilkins (1953)

• X-ray crystallography • 1962 – Nobel Prize awarded to three men• Chargaff – DNA base ratios• Structural model of DNA developed

• DNA Revolution – Promise and Controversy!!!

• Scientific foundation of modern biotechnology • based on knowledge of DNA, its replication, repair and use of enzymes to carry out in vitro splicing DNA fragments


• Breaking the Genetic Code – Finding the Central Dogma

• An “RNA Club” organized by George Gamow (1954) assembled to determine the role of RNA in protein synthesis

• Vernon Ingram’s research on sickle cell anemia (1956) tied together inheritable diseases with protein structure

• Link made between amino acids and DNA

• Radioactive tagging experiments demonstrate intermediate between DNA and protein = RNA

• RNA movement tracked from nucleus to cytoplasm site of protein synthesis


• DNA RNA Protein Transcription Translation

Genetic code determined for all 20 amino acids by Marshal Nirenberg and Heinrich Matthaei and Gobind Khorana – Nobel Prize – 1968

• 3 base sequence = codon


Biotechnology Timeline

1750 BC The Sumerians brew beer.

500 BC Chinese use moldy soybean curds as an antibiotic to treat boils

1590 Janssen invents the microscope

1675 Leeuwenhoek discovers cells (bacteria, red blood cells)

1830 Proteins are discovered

1833 The first enzymes are isolated

1855 The Eschirium coli bacterium is discovered


1859 Charles Darwin publishes On the Origin of Species

1864 Louis Pasteur shows all living things are produced by other living things

1865 The age of genetics begins

1902 Walter Sutton coins the term ‘gene’ - proposed that chromosomes carry genes


1910 Chromosomal theory of inheritance proved

1928 Fleming discovers antibiotic properties of certain molds

1941 George Beadle and Edward Tatum propose that one gene makes one protein

1949 Sickle cell anaemia demonstrated to be molecular disease

http://encarta.msn.com/index/conciseindex/5E/MediaMax.asp?pg=3&ti=761575570&idx=461529478

http://encarta.msn.com/index/conciseindex/38/MediaMax.asp?pg=3&ti=761566021&idx=461532483

Biotechnology Timeline 1952 The ‘Waring Blender’

experiment

1953 The double helix is unravelled

1967 The genetic code is cracked

1973 Recombinant DNA technology begins

1975 First international conference on recombinant DNA technology


1975 Monoclonal antibody technology introduced

1975 DNA sequencing discovered

1978 Genentech Inc. established

1978 Genentech use genetic engineering to produce human insulin in E.coli - 1980 IPO of $89

1978 Kary Mullis discovers PCR


1989 The Human Genome Project begins

1990 First use of gene therapy

1990 First product of recombinant DNA technology introduced into US food chain

1993 FDA announces that transgenic food is safe

1994 The FLAVRSAVR tomato - first genetically engineered whole food


1996 First mammal cloned from adult cells

1990s First conviction using genetic fingerprinting

1996 Development of AffymetrixGeneChip

1997 First artificial chromosome

History of Biotechnology 1998 Human embryonic stem cells

grown

1999 Celera announces completion of Drosophilia genome sequence

2000 90% of Human Genome sequence published on web

2001 Human genome project complete

GM Crops World-wideGM Crops World-wide

Over 30 GM Crops.

Including the following: maize, wheat, soya beans, papaya, raspberries, tomatoes, canola, potatoes, peppers, cabbage, cucumber, squash, cotton, grapes, carrots and chicory.

Trees, turf, flowers

GLOBAL AREA OF GM CROPS

30 FOLD INCREASE SINCE 1996

Global Arear of GM Crops, 1996 to 2001

1.7

11

27.8

39.944.2

50

0

10

20

30

40

50

60

1 2 3 4 5 6

YEARS

1

2

3

4

5

6

Source: Clive James, ISAAA

Where are we with GM crops world wide?

GM crop planting globally increased by 11% in 2000 and >10% in 2001. It has slowed down due to slow development of new markets and lack of products with consumer benefit

More developing countries are commericalising and investing in crop biotech

China wants to be the Asian centre of excellence

Between 1997 and 1999 China approved 26 applications for commercialisation of GMOs, 59 for environmental releases and 73 for field trials

India increasing investment in genomics and biotech ($85 million on genomics in next 5 years)

Genetic Engineering Example: Researchers at Jawaharlal Nehru University in India have developed a genetically

engineered potato that produces about one-third to one-half more protein than usual, including substantial amounts of all the essential amino acids.

Protein deficiency is widespread in India and potato is the staple food of the poorest people.

The “protato” was developed by a coalition of Indian charities, scientists, government institutes and industry as part of a 15-year campaign against childhood mortality.

The campaign aims to eliminate childhood mortality by providing children with clean water, better food and vaccines.

The protato includes a gene from the amaranth plant, a high-protein grain that is native to South America and widely sold in Western health-food stores.

The protato has passed preliminary field trials and tests for allergens and toxins. Final approval from the Indian Government is probably at least five years away.

24-Jan-06 BINASIA - INDIA 31

Blooming Biotech

0 50 100 150 200 250 300 350

Egypt

Cuba

South Africa

Brazil

India

China

South Korea

1991 2002

Number of health-biotechnology papers published by developing countries

Source: The Economist – Dec 11, 2004; Institute for Scientific Information; Science Matrix


Number of health-biotechnology patents (Major developing countries) issued by US in 2003

0 5 10 15 20 25 30 35

Egypt

South Africa

Cuba

Brazil

China

South Korea

India

Source: The Economist – Dec 11, 2004; Institute for Scientific Information; United States Patent and Trademark Office


Agriculture Biotechnology - Crops

Focus :- Improved Productivity

- Drought, Salinity Tolerance- Reduced Yield due to Pests/Diseases - Nutritional Enhancement

Crops :- Rice, Wheat, Cotton, Mustard , Chickpea,

Potato Pigeonpea, Mungbean, Sugarcane

Strategy :- Transgenics & Marker based Molecular Breeding- Cloning and Characterization of New Genes and

Promoters


Crops

Wheat Rust: Durable resistance to leaf and stripe rusts using molecular marker technology in bread wheat (DWR,DWR-RS, PAU, ARI & NCL)

Rice: Salinity and dehydration stress tolerance: Cloning of responsive genes, their promoters and development of transgenics (ICGEB, UDSC, IARI, BI, UOH)

Sugarcane: 12,956 EST’s generated and deposited in genbank. 9000 genomic clones and several thousand cDNA clones developed from high sugar and red-rot resistant lines

Crop Improvement for Better Nutrition in rice, sweet potato and cassava using AmA1 Gene

Use of molecular marker technology approach in wheat quality breeding


Transgenic Research in India

Target Crops/ Vegetables

Cotton, Corn, Mustard, Rice, Soybean, Potato, Tobacco, Coffee, Tomato, Brinjal, Cauliflower, Pea, Cabbage, Banana, Muskmelon, Pigeonpea, Chickpea, Bell-pepper, Blackgram, Chilli, Watermelon etc.

Transgenes Employed

Bt. toxin genes, Herbicide tolerant genes (CP4 EPSPS, Bar gene), Xa21, ctx-B and tcp of V.cholera, Chitinase, Glucanase, ACC synthase, RIP, Protease Inhibitor, Lectin, Ama-1, OXDC gene, Rabies glycoprotein gene, Bar, Barnase, Barstar, GNA gene, Vip-3 gene, Bacterial Blight Resistance gene, Osmotin etc.


Transgenic Crops under Trial

• Under green house trial : 19• Under limited field trial : 3

(Rice, Mungbean, Mustard)• Large scale field trial : 1

(Cotton)• Released for commercial production : 1

(Cotton)


Plant Biotechnology– Areas : Forestry, Horticulture & Plantation Crops– Status

• 57 regeneration systems documented• Protocols standardized for 20 plant species, 10 technologies

transferred to industry – Eucalyptus, Bamboo, Teak, Sugarcane, Potato, Black pepper, Coffee, Citrus

• Ongoing R&D - Transgenics– Tomato, Grapes, Banana - shelf life– Chilli, Pepper, Ginger, Cardamom – Disease resistance– Populus, leucaena - reduced lignin

• Germplasm characterization – Teak, Eucalyptus, Casurina– International Solanaceae Genome initiative launched

• India to sequence chromosome 5 of tomato• Functional genomics of tomato – nutritional quality, shelf life,

disease resistance – Production and demonstration of quality planting material of Bamboo


Tomato Genome Sequencing

1 2 3 4 5 6 7 8 9 10 11 12

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Animal Biotechnology– Diagnostics for Peste-des-Petitis

Ruminants (PPR) detection commercialized

– Reconstituted Bovine collagen for wound and burn healing commercialized

– Multicentric programme on buffalo genomics launched : Characterisation of traits of economic importance

– Multicentric programme on bovine tuberculosis

– Programme on animal nutrition


Aquaculture & MarineBacterial immunostimulant for shrimp health management developedBioreactor system developed for water quality management in prawn hatcheryNew source of insulin from carp adipose tissueQuality agar extracted from seaweed (Gelidiella acerosa)Efficacy of DNA-based vaccine for Aeromonas infection in carps under

evaluation Shrimp Genomics launched – Comparative and functional genomicsDiagnostics and vaccines transferred to industry

• Immunodiagnostic kit for detection of bacterial pathogens in finfish and shellfish

• Combi kit for simultaneous detection of White Spot Shrimp Virus and Monodon Baculo Virus

• Heat killed whole cell vibrio vaccine, shows immune response in shrimp • Immunodot detection kit for white spot shrimp virus

Technology ready for transfer• Bioreactor technology in shrimp hatcheries through bacterial

conservation for denitrification


Seribiotechnology

• Improved quality and productivity in silk– Silkworm genome sequencing– Over 400 molecular markers generated – India participating in International Consortium on Lepidopteran

Genomics: More than 10,000 ESTs of muga silkworm and mori silkworm characterized

• Three high yielding hybrids of silkworm released to farmers• Network projects initiated for use of molecular markers in breeding

of disease-resistant silkworm and pest- and disease-resistant mulberry

• Molecular characteriztion of non-mulberry silkworm (Tasar, muga, eri)

• Spider silk– Biophysical properties of spider silk proteins produced by

Indian species– Sourcing of spider silk genes and expression in Bombyx mori– Prospecting of Indian spiders venom for therapeutic purposes– Application of nanobiotechnology to spider silk


Medicinal & Aromatic Plants• Four national gene banks established - about 3500 accessions • Two specialized germplasm banks set up for plants used in Indian

System of Medicines• Production of high value therapeutic compounds in cell culture

(Podophyllotoxin, guggulsterones Z&E, camptothecin and azadirachtin)• Isolation and characterization of new thereapeutic leads (for anticancer,

antiamoebic, antidiabetic, bioenhancers, immunomodulatory).• Clinical trial of standardized herbal preparations - Terminalia arjuna – left

ventricular dysfunction• Five technologies transferred to industry; several other leads under

discussion with industry• Herbals for veterinary health care - priorities identified • Functional genomics of selected medicinal and aromatic plants• Plants as bioreactor for production of biomolecules (antigens for cholera,

rabies), antibodies for therapeutics and industrial enzymes


Biofertilizers • 23,000 ha demonstrated for use of

biofertilizers; 50,000 farmers benefited• 10 packages for Integrated Nutrient

Management developed for specific cropping system of varied agroclimatic zones

• A network project on development of efficient strains of biofertilisers launched at 11 centres

• Liquid biofertilizer technology – being developed


Biopesticides• Technology Development and Demonstration

– 24 Integrated Pest Management technology packages developed; 7 transferred to industry

– Over 150,000 ha covered in different agroclimatic zones; 65,000 farmers benefited

– Insect sex pheromones successfully synthesized and field-tested for the mass trapping of brinjal shoot and fruit borer

– More than 615 plant extracts prospected as source of pesticides; 11 promising leads short listed for further investigation

• Product Development– ‘Bioprahar’: biopesticide (for cabbage and

cauliflower) developed by ICGEB, launched commercially (2004)


Bioprospecting– Bioprospecting of genes / molecules –

• 96 stress related genes identified, characterized and cloned, salt resistance gene transferred to rice and mung bean, field trials of transgenic rice being conducted

• Product development –

– Microbial biofertilizers for coastal region

– Biopesticide for bollworm (Helicoverpa)

– SOD antioxidant – skin cream

– Over 4000 plant species from Western Himalayas and Western ghats screened for natural dyes; nine short listed as potential sources

– Network project on lac biotechnology initiated

– Chemical and genetic profiling, conservation –

6 endangered medicinal plant species


Microbial Diversity– Arid Zones : 48 Saline tolerant algal species, screened for pigment

production, soil conditioning and nitrogen fixation– Cold Habitats : > 100 bacterial species isolated from soil and water

samples from Antarctica – Hot Springs and sulfur springs : > 150 Actinomycetes species isolated,

potential rifamycin producer identified– Hydrocarbon contaminated Sites : 12 oil refineries screened, > 350

bacteria species isolated, thermophilic Bacterial consortium developed for enhancing Oil recovery from Oil wells

– Marine Sources: > 500 Bacterial isolates screened for secondary metabolites, benzoate and phenol degraders identified

– Forest Belts: Virgin ecosystems, novel entomopathogenic and keratinolytic fungi Isolated and identified

– Enhancement of Oil Recovery from dead Oil wells - Bacterial Consortium developed which on being injected in sick oil wells under high pressure leads to oil recovery, tested in 25 Oil Wells of ONGC, helped in extraction of 4500 cubic meters of oil worth US$675000


Environment Biotechnology• Conservation of endangered animals – especially big

cats – through embryo transfer technology and tissue banking

• Use of lichens as indicators of environmental pollution• Bioremediation of degraded ecosystems • Green technologies to treat industrial effluents (paper

& pulp, dyes, distilleries, tanneries etc)• Bioscrubber for removal of obnoxious industrial

emissions• 14 technology packages developed; 5 under use by

industry• Programme on microbial approaches to combat global

warming


Medical Biotechnology

• Vaccines• Diagnostics• Therapeutics• Stem Cell Technology• Biomedical Engineering• Nanomedicines• Clinical Trials and Clinical Research


Vaccines• Rabies : DNA vaccine, phase III animal

trials completed.• Cholera : Recombinant oral vaccine,

Phase II trial.• Malaria : Phase I clinical trials initiated.• Rotavirus : Phase I clinical trials underway• JEV : Vaccine technology transferred to

industry• HIV/AIDS : DNA candidate for subtype ‘C’

developed • Anthrax : Phase III clinical trials initiated. • Infectious Bovine Rhinotracheitis : Commercialised

(cattle)


Diagnostics

Transferred to the Industries & Launched in the Market :

Western Blot for HIV-I & II : HIV/AIDS

Naked Eye Agglutination : HIV/AIDSSystem (NEVA)

ELISA : Hepatitis ‘C’ ELISA :

Leishmaniasis ELISA : Alpha-feto

Protein

(Pregnant Women)

Transferred, yet to be launched :

IgM Mac ELISA : DengueJapanese

EncephalitisWest Nile

IgM – ELISA : Hepatitis ‘A’ Urine Based ELISA : Reproductive

Hormones

Under Development & Negotiations

for Transfer : DAT :

Toxoplasmosis Haemagglutination Assay :

Leishmaniasis IFA : Rabies Species Specific Tests : Snake

Bites PCR Assay : Tuberculosis Multiplex PCR : STD PCR : Leptospirosis In-vitro Assay : Anti-Inflammatory

Drugs Immunochromatogrpahy/ :

Tuberculosis / ELISA Assay PCR Assay : Typhoid


Biotech Products in Indian market

• r DNA Hep ‘B’ vaccine• Recombinant streptokinase• Erythropoietin• α, β, γ – interferon• Haemophilus influenzae B vaccine• Human insulin• Human Growth Hormone• Human Interleukin• Streptokinase • Granulocyte Colony Stimulating Factor • Follicle Stimulating Hormone• Tissue Plasminogen Activator


Indian Biotechnology IndustryNumber of biotech companies : 300Global ranking in terms biotech companies : 11Investment growth in last 5 years : 50 % per annumAnnual Turnover (Apr 04 – Mar 05) : US $ 1.07 BillionAnnual increase : 37 %Percentage of global business (2004-05) : 1.6 %

(2003-04) : 1.5 %(2002-03) : 1.2 %

Exports : 43 %Major areas : Biopharma, Bioservices, Bioindustries,

Bioagriculture, bioinformatics, Biosupplies