Introduction to chemical engineering

Biotechnology and the

role of chemical
engineers
 In the CBI Program we study …
How proteins work: structure is related to function.

Lila Gierasch
How do chains of amino acids fold in 3D
to make active proteins inside the cell?

Igor Kaltashov
How is the ability of transport proteins to bind and
release ligands when necessary controlled by their
environment?
 Complexity – Difference in Weight
The molecular weights (in daltons, the standard unit of
molecular mass) of some popular drugs:
Source: Lisa Raines, Genzyme 2001

Chemical Biotechnology products

Glucophage® 166 Neupogen® 18,800

Vioxx® 314 Intron-A® 19,625

Prozac® 346 Humatrope® 22,125

Zantac® 351 Avonex® 22,500

Paxil® 375 Epogen® 30,400

Claritin® 383 Pulmozyme® 37,000

Zocor® 419 ReoPro® 47,615

Augmentin® 420 Enbrel® 75,000

Crixivan® 712 Zenapax® 144,000

Taxol® 854 Rituxan® 145,000

 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 (AccesExcellence)
 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? 
• GMO - genetically modified organisms
• GEO - genetically enhanced organisms

• In both cases, the natural genetic material of the

organism has been altered.

• Roots in bread-making, wine brewing, cheese and

yogurt fermentation, and classical plant and animal
breeding
 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
 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
 Ancient biotechnology 
Fermented foods and beverages

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

Chemical transformations to produce therapeutic

products

• Substrate  + Microbial Enzyme  Product

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

Microbial synthesis of other commercially valuable

products

• Amino acids to improve food taste, quality or

preservation

• Enzymes (cellulase, collagenase, diastase,

glucose isomerase, invertase, lipase, pectinase,
protease)

• Vitamins

• Pigments
 Modern biotechnology 
• 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

• Griffith’s 1928 experiment

• Bacterial transformation of S. pneumoniae
from rough to smooth
• 1944 – Avery, MacLeod and McCarty
identify transforming principle as DNA
 Modern biotechnology 
• 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

• Messelson and Stahl

• 14N/15N  semi-conservative replication
confirmed
• 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
 Modern biotechnology 
• 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
 Modern biotechnology 

• 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

 What are the areas of biotechnology? 

• Organismic biotechnology
• uses intact organisms and does not alter genetic
material

• Molecular Biotechnology
• alters genetic makeup to achieve specific goals

Transgenic organism: an organism with artificially

altered genetic material
 What are the benefits of 
biotechnology? 
• Medicine
• human
• veterinary
• biopharming

• Environment
• Agriculture
• Food products
• Industry and manufacturing
What are the applications of  biotechnology? 

• Production of new and improved crops/foods,

industrial chemicals, pharmaceuticals and livestock
• Diagnostics for detecting genetic diseases
• Gene therapy (e.g. ADA, CF)
• Vaccine development (recombinant vaccines)
• Environmental restoration
• Protection of endangered species
• Conservation biology
• Bioremediation
• Forensic applications
• Food processing (cheese, beer)