Chapter . 1 INTRODUCTION TO BIOTECHNOLOGY

 

INTRODUCTION: The term biotechnology was introduced in 1919 by a Hungarian engineer, Karl Ereky. He used the term for large-scale production of pigs by using sugar beets as the source of food.  According to Ereky, all types of work are biotechnology by which products are produced from raw materials using living organisms.  Eg.  yogurt, vinegar, alcohol, wine and cheese.  Biotechnology is one of the world's fastest growing and most rapidly changing  technology.

The Spinks Report (1980) defined  biotechnology as the application of biological organisms, system or processes to the  manufacturing and service industries. Biotechnology is used in the field of pharmaceuticals such as  microbiology. biology, biochemistry, biophysics, cell biology, genetics, molecular biology.  engineering technology etc. 

Branches of  biotechnology.

1) Bioinformatics : It is an interdisciplinary field which addresses biological  problems using computational techniques, and makes the rapid organization and analysis of  bioiogical data. Bioinformatics plays a key role in genomics and proteomics

2) computational biology : it is  defined as, "conceptualizing biology in terms of molecules and then applying informatics  techniques to understand and organize the information associated with these molecules."

3) Blue biotechnology is used to describe the marine and aquatic  applications of biotechnology.

4) Green biotechnology is biotechnology applied  to  agricultural processes. Eg. The designing of transgenic plants to grow

5) Red biotechnology is applied to medical processes. Eg. Antibiotics

6) White  biotechnology, also known as industrial biotechnology, is biotechnology applied to  industrial processes. Eg. enzymes and proteins . 

The investment and economic output of all of these types of applied biotechnologies is  termed as bioeconomy. 

MILESTONES IN BIOTECHNOLOGY: The term biotechnology was described in a bulletin of the Bureau of Biotechnology published in 1920.

1. Pasteur proposes that microbes that cause fermentation-1857

2. Discovery of genetic basis of heredity by Gregor Mendel. 1860

3. Fleming discovers chromation, i.e. chromosomes. 1879 

4. The first cancer causing virus is discovered by Rous. 1911 

5. Microbes are used to treat sewage for the first time in Manchester, England. 1914  6. Develop of fermentations process for acetone &n-butanol by Chain Weizmann. 1916 

7. Discovery of penicillin by Alexander Fleming.  1929

8. Discovery of streptomycin by Selman Waksman.  1943

9. DNA is proven to carry genetic information.  1944

10. Elucidation of double helical structure of DNA by FrancisCrick & James Walson. 1953 

11. Mechanism of DNA replication was studied in E. coli by Meseleson and Stahl. 1958 

12. Determination of genetic code by Nirenberg and Mathaei. 1961

13. DNA transformation into E. coli. 1970 

14. Preparation of monoclonal antibodies using hybridoma cells by Cesar  Milstein and George Kohler.  1975 

15. Sequencing of  DNA by Sanger and Coulson.  1975

16. Genetically engineered microorganisms can be patented (US Supreme Court).  1980 Development of Gene Bank.  1982

17. Discovery of PCR.  1985

18. Development of human genome project.  1990 

19. Complete sequencing of yeast genome.  1996 

20. Dolly (sheep), first cloned animal.  1998 

21. Maintenance of human stem cells in culture. 1998 

22. Human genome, the first mammalian genome sequenced. 2001

23. Discovery of restriction enzymes. 1971 

Human  Insulin (Humulin) is the first pharmaceutical product derived from DNA technology which  was discovered by Genetech and Eli Lilly and Company in 1882 and this product has been  approved by US FDA.

Generic name	Product name	Name of company	Year
Human insulin	Humulin	Eli Lilly	1982
Sometrem	Protropin	Genetech	1985
Digoxin Immune Fab	Digibind	Burroughs Wellcome	1986
Interferon- α 2a	Roferon-A	Hoffmann - La- Roche	1986
Interferon-α - 2b	Intron-A	Schering- Plough	1986
Hepatitis-B-vaccine	Recombivax HB	Merk	1986
Somatotropin	Humatrope	Eli Lilly	1987
Heamophilus-B-conjugate	Hib. Titer	Praxis Biologics	1988
Vaccine	-	-
Hepatitis-B-vaccine	Engerix-B	SmithKline Beecham	1989
Interferon-y-lb	Actimmune	Genetech	1990
Sargramostim	Leukin	Immunex	1991

 

SCOPE AND APPLICATIONS IN PHARMACEUTICAL SCIENCESS 

Biotechnology is the applied science and has made many advances in different fields. 

1) Recombinant DNA technology: -The production of human insulin by recombinant DNA techniques was an early goal for the pharmaceutical industry. This technique has been used  to produce number of natural proteins, vaccines and enzymes. Various diagnostic kits have  been developed such as tumour kits, pregnancy testing, ovarian cancer detecting test  immunoradiometric assay kits etc. 

2) Gene therapy:

- Inserting a missing gene or replacing a defective one in human cells is  an important outcome of gene therapy.

-This technique uses a harmless virus to carry the  missing a new gene into the appropriate chromosome.

- Gene therapy has been used to treat  patients with adenosine deaminase (ADA) deficiency, a cause of severe combined  immunodeficiency disease (SICD), in which cells of immune system are missing or inactive. 

- Spliceosome-mediated RNA trans-splicing (SMaRT) is a new technology for gene therapy  that exploits the expressed genetic differences between normal and diseased cells. It is used in Cystic fibrosis, duchenne muscular dystrophy (DMD), spinal muscular  atropy (SMA)

This  technology may be applied to a wide range of diseases that involve the expression of unique  or mutated genes.

3) Molecular markers:

-It has  ability to monitor the expression of essentially the whole  genome in the form of individual mRNA levels for a wide variety of situations and settings. 

-It uses multi-variant biomarker strategies for every step in the drug discovery and development process. It monitor the expression  of large set of genes.

- It is used in the identification and validation of drug targets. 

Eg Polymerase chain reaction (PCR), used to identify  the presence of infections such as AIDS, Chlamydias and other microbial diseases.

4) Criminal forensic: DNA fingerprinting is the process of cross matching two strands of DNA. In criminal investigations, DNA from samples of hair, body fluids or skin at a crime scene is compared with those obtained from the suspects.

 5) Monoclonal biotechnology: 

Antibodies are glycoproteins that can be made to specifically target the immunizing agent. They are also being used to detect  Monoclonal allergies, anaemias and heart diseases, hepatitis, gonorrhoea, syphilis, streptococcal infections, AlDS etc

6) Genetically engineered vaccine:

The first genetically engineered vaccine was in US in 1986 for approved hepatitis B. Genetic engineering allows large scale production of the protein components of a virus. Many vaccines are under development for humans production of against influenza, rabies, hepatitis, herpes simplex, poliomyelitis etc.

7) Plant tissue culture: Plant tissue culture is the technique of and growing plant cells, tissues. Many natural products are prepared by plant tissue culture such as vincristine, vinblastine, opium alkaloids, digitalis glycosides etc. The method of immobilized plant cells has been found very effective for the production of secondary metabolites. Animal cell culture deals with the study of organs, tissues or individual cells in-vitro. Antibodies, enzymes, hormones, cytokines etc. are produced by animal cell culture techniques.

8) Genetically engineering plants: Genetically engineering plants are also poised to produce vaccines. Bacillus thuringiensis produce proteins that kill certain insects such as lepidopterans (tobacco budworm, armyworm), coleopterans (beetles) and dipterans (flies, mosquitoes). B. thuringiensis forms protein crystals during a particular phase of their growth. These crystals contain a toxic insecticidal protein. The Bt toxin protein exist as inactive protoxins but once an insect ingest the inactive toxin, it is converted into an active form of toxin due to the alkaline pH of the gut which solubilise the crystals. The activated toxin binds to the surface of midgut epithelial cells and create pores that cause cell swelling and eventually cause death of the insect. Bt toxin gene has been cloned from the  bacteria and been expressed in plants to provide resistance to insects without the need for insecticides 

9)Genetically engineered animals: Animals that have had their DNA manipulated to possess and express an extra (foreign) gene are known as transgenic animals. Transgenic rats, rabbits, pigs, sheep, cows and fish have been produced. These are specially made to serve as models for human diseases such as cancer,  cystic fibrosis, rheumatoid arthritis and Alzheimer's so that investigation of new treatments  for diseases is made possible. Transgenic animals that produce useful biological products  can be created by the introduction of the portion of DNA which codes for a particular  product such as human protein (a-antitrypsin) used to treat emphysema. In 1997, the first transgenic cow, Rosie, produced human protein-enriched milk. The milk contained the  human alpha-lactalbumin and was nutritionally a more balanced product for human babies  than natural cow-milk. Transgenic mice are being developed for use in testing the safety of vaccines before they are used on humans eg.polio vaccine. Transgenic animals are made that carry genes which make them more sensitive to toxic substances than non-transgenic animals. Toxicity testing in such animals will allow to obtain results in less time. 

10) Pharmacogenomics: Using pharmacogenomics, pharmaceutical companies can create drugs based on the  proteins, enzymes and RNA molecules that are associated with specific genes and diseases.  These tailor-made drugs not only to maximize therapeutic effects but also to decrease  damage to nearby healthy cells. The discovery of potential therapies will be made easier  using genome targets. Genes have been associated with numerous diseases and disorders.  With modern biotechnology, these genes can be used as targets for the development of  effective new therapies, which could significantly shorten the drug discovery process. 

11) Bioinformatics:.  Being an interface between modern biology and informatics it involves discovery,  development and implementation of computational algorithms and software tools that  facilitate an understanding of the biological processes with the goal to serve primarily  agriculture and healthcare sectors with several spinoffs. In the pharmaceutical sector, it can  be used to reduce the time and cost involved in drug discovery process, to custom design drugs and to develop personalized medicine. Computer aided drug design (CADD) is a specialized discipline that uses computational methods to simulate drug-receptor interactions. CADD methods are heavily dependent on  bioinformatics tools, applications and databases. 

12) Human Genome Project (HGP): The Human Genome Project (HGP) is an attempt to map completely the entire spectrum of genetic materials that can be found in all human beings. It is used to determine the complete sequence of the DNA from a typical human cell and it provides information and resources to understand some of the critical differences the that make us individuals and that often contribute to diseases.