BIOTECHNOLOGYPrinciples, Applications,and Social Implications

General DefinitionThe application of technology to improve a biological organism

Detailed DefinitionThe application of the technology to modify the biological function of an organism to produce useful usually commercial products

But we know nature does not have all of the traits we need

• Here we see bean has many seedcoat colors and patterns in nature

•Nature has a rich source of variation

These definitions imply biotechnologyis needed because:

But nature does not contain all thegenetic variation man desires

•Fruits with vaccines

•Grains with improved nutrition

GENOMICSDNA and Genetic Engineering

Genomics

• the study of genomes• a broad field that encompasses

whole-genome comparisons, structural analysis of gene products, and surveys of small-scale variations in sequence

DNA Profiling• identifying an individual by analyzing

the unique parts of his or her DNA

Short tandem repeats• in chromosomal DNA, sequence of 4

to 5 bases repeated multiple times in a row

DNA Cloning

• uses living cells to mass-produce particular DNA fragments

Recombinant DNA

• a DNA molecule that contains genetic material from more than one organism

Restriction enzyme

• type of enzyme that cuts specific nucleotide sequences in DNA

Cloning vector

• a DNA molecule that can accept foreign DNA and get replicated inside a host cell

Genetic Engineering• process by which deliberate changes

are introduced into an individual’s genome.

Genetically modified organism (GMO)

• organism whose genome has been modified by genetic engineering

Transgenic• refers to a genetically modified

organism that carries a gene from a different species

Gene therapy

• the transfer of recombinant DNA into an individual’s body cells, with the intent to correct a genetic defect or treat a disease.

Gene therapy is the use of DNA as a drug to treat disease by

delivering therapeutic DNA into a patient's cells. The most

common form of gene therapy involves using DNA that

encodes a functional, therapeutic gene to replace a

mutated gene.

In gene therapy, DNA must be administered to the patient, get to the cells that need repair, enter the

cell, and express a protein. Generally the DNA is incorporated into an

engineered virus that serves as a vector, to get the DNA through the

bloodstream, into cells, and incorporated into a chromosome.

Severe Combined Immunodeficiency Disorder (SCID)• a severe x-linked genetic disorder

due to mutated allele; infected individuals can survive only in germ-free environment due to impairment of the immune system

ANTIBIOTICS

SOME GENERAL PRINCIPLES

• Antibiotics can be naturally produced, semi-synthetic, or synthetic substances

• Designed to have as much selective toxicity on the bacteria as possible

EXAMPLES OF SELECTIVE ACTION

• Penicillin on bacterial cell wall (organisms without cell wall won’t be inhibited eg Mycoplasma pneumoniae)

• Sulphonamides prevent bacteria synthesising folic acid whereas humans can use preformed folate

• Generally drugs acting on cell membranes or protein synthesis are more toxic to humans

ANTIBIOTICS ACTING ON CELL WALL OF BACTERIA

• Beta lactams:• Penicillins, cephalosporins, carbapenems,

monobactam

• Glycopeptides:• Vancomycin, teicoplanin

PENICILLIN

• They act by inhibition of bacterial cell wall synthesis, thus exposing the osmotically less stable membrane

• These agents are bactericidal• Active against multiplying and not resting

bacteria; inactive against mycobacteria, protozoa, fungi and viruses

Penicillin G (Benzyl penicillin)Highest activity against Gram-positive organisms but susceptible to Beta-

lactamase. Effective against :Gram-positive aerobic cocci - Staph. aureus- not producing penicillinase,

S.pneumoniae ( group A ) ,S.pyogenes Gram-negative aerobic cocci -N.meningitidis

Gram- positive bacilli : Bacillus anthracis Anaerobes Clostridium spp but inactive against B.fragilis Actinomycetes israelii ( actinomycosis )

Penicillin G benzathin

Duration 3- 4 weeks Painful at the injection site ( limits its use ) Uses 1. Syphilis 2. Rheumatic fever prophylaxis( inhibits group A beta- hemolytic streptococci) 3. Streptococcal pharyngitis

Disadvantages of penicillin G

A. Destroyed by gastric HCLB. Inactivated by penicillinaseC. Narrow spectrum of activity

Phenoxy- methyl penicillin ( penicillin V)

Acid resistant penicillins ( spectrum of activity is similar to penicillin G )UsesGroup A Streptococcal pharyngitisProphylaxis against group A streptococci in points with

history of rheumatic heart disease.DisadvantagesReadily hydroyzed by beta-lactamase

Penicillinase-resistant penicillins

Are the choice for infections caused by

penicillinase producing S. aureus.

• Methicillin • Dicloxacillin• Floxacillin• NafcIlli• Oxacillin• Cloxacillin

Broad- spectrum penicillins

Less active than penicillin G against

G+ cocci. Active against G- organisms.

• Ampicillin • Ampicillin-

sulbactam• Bacampicillin• Amoxicillin• Amoxicillin-

clavulanic acid ( augmentin )

USES

• H. Influenza infections (otitis media, sinusitis, chronic bronchitis, pneumonia, bacterial meningitis ).

• E. Coli infections (Urinary & biliary infections)• Samonella infections (typhoid fever)• Shigella infections (ampicillin)• Gonococcal infections (alternative for

penicillin in the treatment of gonorrhea)

DISADVANTAGES

• Amoxicillin & ampicillin alone are readily destroyed by Staph. Penicillinase

Adverse effects of penicillins

1.Hypersensitivity reactions Urticarial rash Fever Bronchspasm Serum sickness Exfoliative dermatitis Stevens- Johnson syndrome Anaphylaxis2. Super infections3. Diarrhoea4. May cause convulsions after high doses by i.v or in

renal failure

Some clinically important antibiotics

Antibiotic Producer organism ActivitySite or mode of

action

Penicillin Penicillium chrysogenumGram-positive bacteria

Wall synthesis

CephalosporinCephalosporium acremonium

Broad spectrum Wall synthesis

Erythromycin Streptomyces erythreusGram-positive bacteria

Protein synthesis

Streptomycin Streptomyces griseusGram-negative bacteria

Protein synthesis

Tetracycline Streptomyces rimosus Broad spectrum Protein synthesis

Vancomycin Streptomyces orientalisGram-positive bacteria

Protein synthesis

THE IDEAL ANTIBIOTIC?:PENICILLIN

• Bactericidal• Widely distributed in body esp. CNS• Excreted by the kidneys