What is Biotechnology?

• Biotechnology is the study and manipulation of

living things or their component molecules, cells,
tissues, or organs for the benefit of humans (or
other animals).
– This term has been used since the 1970’s to reflect
the application of exciting new technologies to the
research and development of products from plant
and animal cells.

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 Biotech Includes (but is not limited to)
• Recombinant DNA (rDNA) technology
• Polymerase Chain Reaction (PCR)
• Cloning
• Fermentation
• The creation of
– Insulin to treat diabetes
– Proteases (enzymes used to remove stains from
clothing)
– Antibodies (for recognizing and fighting certain
diseases
– Selective Breeding (dog breeds, flowers, fruits)
– Pharmaceutical drugs
– Cellular manipulation products (growing human
ears on mice)
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 Examples of Early Biotech
• Historical accounts have shown that the Chinese, Greeks, Romans,
Babylonians, and Egyptians (among many others) have been involved in
Biotech since 2000 BC!
• Early ancestors took advantage of microorganisms and used
fermentation to make breads, cheeses, yogurts, and alcoholic beverages
such as beer and wine.

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 Fermentation
Fermentation is when strains of yeast
decompose sugars to derive energy, and in
the process they produce ethanol (alcohol)
and carbon dioxide as a waste product.
– When bread dough is being made, added yeast (saccharamyces
cerevisiae) ferments sugar releasing carbon dioxide, which causes
the dough to rise and creates holes in the bread. The alcohol
produced by the yeast evaporates when the bread is cooked.
– When making cheese, added bacteria undergo
fermentation by breaking down Lactose (milk
sugar) and converting it to Lactic Acid which
causes the milk to curdle and form cheese!

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 Antibiotics
• In 1928 Alexander Fleming discovered that
mold Penicillium inhibited the growth of
Stapholococcus aureus. His discovery came
from a pile of “contaminated” Petri dishes.

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 Viral Vaccines
Edward Jenner was an English country doctor
who pioneered vaccination. Jenner's
discovery in 1796 that inoculation with
cowpox gave immunity to smallpox, was an
immense medical breakthrough and has
saved countless lives.

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More Current Examples of Biotechnology
• In 1972 the DNA composition of humans is
shown to be 99% similar to that of chimps and
gorillas
• In 1981 the first genetically-engineered plant is
reported and the 1st mouse was successfully
cloned
• In 1982 Humulin (a human insulin drug), was
produced by genetically-engineered bacteria
and was the first biotech drug approved by the
FDA

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• In 1994 the first breast cancer gene is discovered
• In 1996 scientists clone identical lambs from early
embryonic sheep
• In 1998 embryonic stem cells are used to
regenerate tissue and create disorders that
mimic diseases

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 The Human Genome Project
• The Human Genome Project (HGP) was an
international, 13 year effort that began in
1999 and was completed in 2003. The project
goals were to
• Determine the complete sequence of the 3 billion DNA
subunits (bases)
• Identify all human genes, and make them accessible for
further biological study.
– As part of the HGP, parallel sequencing was done for
selected model organisms such as the bacterium E.coli
to help develop the technology and interpret human
gene function.
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 Domains of Biotechnology

The domain areas in Biotechnology can be

simplified into eight different concentrations
1. Microbial
2. Agricultural
3. Animal
4. Forensic
5. Bioremediation
6. Aquatic
7. Medical
8. Regulatory

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• Microbial Biotechnology: The manipulation
of microorganisms such as yeast and
bacteria. Example: Fermentation
• Agricultural Biotechnology: The genetic
engineering of plants in hopes of
– Giving the plant pest resistance
– Producing foods with a higher protein or vitamin
content
– Developing drugs that can be grown and isolated in
plant products

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• Animal Biotechnology: This branch includes
– Using animals as a source of medically valuable
proteins
• Antibodies
– Using animals as an important model in basic
research
• Gene “knockout” experiments (where genes have been
turned off)
• Designs and testing of drugs and genetic therapies
– Animal cloning
• Source of transgenic organs (animal organs that can be
transplanted into humans without fear of rejection).

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• Forensic Biotechnology
– DNA fingerprinting
• Inclusion or exclusion of a person from suspicion
• Paternity cases
• Identification of human remains
• Endangered species
• Tracking and confirmation of the spread of disease

• Bioremediation
– The use of biotechnology to process and degrade a variety of natural and
manmade substances
• Particularly those that contribute to pollution
– For example, bacteria that degrade components in
crude oil
• 1989 Exxon Valdez oil spill in Alaska
• Gulf Oil Spill

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• Aquatic Biotechnology
– Aquaculture – raising finfish or shellfish in controlled conditions for use
as food sources
• 30% of all fish consumed by humans worldwide
– Genetic engineering
• Disease-resistant strains of oysters
– Vaccines against viruses that infect salmon and
other finfish
– Rich and valuable sources of new genes, proteins and metabolic
processes with important applications for
human benefits
• Marine plankton and snails found to be rich sources of anti-tumor
and anticancer molecules

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• Medical Biotechnology
• Involved with the whole spectrum of human medicine
• Preventive medicine
• Diagnosis of health and illness
• Treatment of human diseases
• New information from Human Genome Project
• Gene therapy
• Stem cell technologies
• Regulatory Biotechnology
– Quality Assurance (QA)
• All activities involved in regulating the final quality of
a product
– Quality Control (QC)
• Part of QA process that involves lab testing and
monitoring of processes and applications to ensure consistent
product standards

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Tools of Biotechnology
1. Bioprocessing technology
• Using whole living cells or components of them to
manufacture desired products.
• Most common whole cells used are yeast and
bacteria (one-celled organisms).
• Most common components are enzymes
(proteins that catalyze chemical reactions).
• Microbial fermentation
• Cells isolated from animals and plants also are
used to produce desired products.

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Tools of Biotechnology
2. Genetic engineering
• The technique of removing, modifying or adding
genes to a DNA molecule to change the information it
contains.

• Is known more specifically as recombinant DNA

(rDNA) technology.

• The product of rDNA technology is known as a

genetically modified organism, or GMO.

• Example: Gene for human insulin inserted into E.coli

→ bacteria that make human insulin (a
biopharmaceutical).
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 Definition of biologics

„A biological medicinal product is a product, the active substance of

which is a biological substance. A biological substance is a
substance that is produced by or extracted from a
biological source and that needs for its characterisation and the
determination of its quality a combination of physico-chemical-
biological testing, together with the production process and its
control.” 18
COMMISSION DIRECTIVE 2003/63/EC, 3.2.1.1. b,
 Types of biologics

Biologics Blood or blood components

Recombinant DNA
Advanced therapy
products
medicinal products
Therapeutic proteins
Somatic cell therapy

Monoclonal antibodies
Gene therapy

Tissue engineering Fusion proteins

Xenotransplantation

Vaccines Allergenic products

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COMMISSION DIRECTIVE 2003/63/EC, 3.2.1.1. b,
 Biologics vs. Small molecule
drugs

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Source: Cecil Nick, TOPRA 2010
 Biologics vs. Small molecule
drugs
Small molecule
Biologics
drugs
Extracted from biological source or
Production Chemical synthesis
recombinant DNA techology
> 10 kDa
Molecular weight < 10 kDa

Administration route Mainly oral route Mainly parenteral route

Could elicit immunological
Immunogenicity Not an issue
response
Follow-up molecules Generics Biosimilars

IN SUMMARY, biologics are protein-like macromolecules.

 Potential risk: immunogenicity
 Parenteral administration
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 Biotechnology in medicine

Milestones in medical
biotechnology
Achievements, paradigm shifts

Current trends and research

Conclusions

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 Major milestones in medical
biotechnology
Escherichia coli (E. coli) bacterium discovered (later becomes a major
1855 tool for biotechnology).
Cohen and Boyer develop genetic engineering techniques to "cut
1973 and paste" DNA and reproduce the new DNA in bacteria.

1975 Köhler and Milstein: hybridoma technology (Nobel prize 1984).

1977 Genentech scientists and their collaborators produce the first human
protein (somatostatin) in a bacterium (E. coli).
1982 Eli Lilly and Company markets recombinant human insulin - the first
such product on the market.
1986 First therapeutic monoclonal antibody approved by FDA (muromonab
for organ transplant rejection prevention).
2009 First tissue engineered product approved in the EU (ChondroCelect).

2012 First gene therapy approved in the EU (Glybera).

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Recombinant DNA products

E. coli

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Recombinant DNA products
manufacturing process

Cell lines
•Prokaryotic (e.g. E. coli)
•Eukaryotic (e.g. Chinese Hamster Ovary)

Multi-step manufacturing process

1. Cell line genetic cloning and selection
2. Upscale (= fermentation)
3. Downscale (= purification)
4. Formulation
5. Fill and finish

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 Important therapeutic fields of
recombinant DNA products
Oncology

Psoriasis

Autoimmune diseases Rheumatology

Inflammatory bowel diseases

Endocrinology
Ophtalmology
Cardiology Asthma

Transplantation medicine Haematology

Neurology

Infectious diseases Intensive care

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