Biotechnology BIO3103M/

Introduction to Biotechnology
BGY9002M
A Brief History of Biotechnology

James Flint: jflint@lincoln.ac.uk

 Lecture 2
Ancient Biotechnology
Immunization
Monoclonal antibodies
The Molecular Biology Revolution
The Genomic Revolution
Synthetic Life

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Ancient Biotechnology (I)
Module Aims

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Agriculture is Biotechnology
60 UK breeds
of sheep

Brindled Shorthorn Cow, bred at Calke

(Thomas Weaver, 1931) 4
 Ancient Biotechnology (II)

(~4000 BC, Egypt)

(~5-6000 BC,
Saccharomyces cerevisiae
Georgia, Iran)

Food of the Gods (~5500 BC, Poland)

Lactobacillus delbrueckii
(~500 BC,
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India to Persia) Salque et al., (2012) Nature 493, 522-525.
 Control of microbial
infection: immunisation
(1798)
Immunization developed by Edward
Jenner
Inserted pus taken from a cowpox pustule into an incision on
a boys arm (James Phipps)
Two months later injected boy with pus taken from a smallpox
pustule No disease developed
Jenner concluded protection was complete
Jenner coined term vaccine from Latin vacca (cow)
Widespread use of vaccination adopted from ~1800
Smallpox declared irradicated globally in 1980 (World Health
Organization) 6
 Fleming and Penicillin (1928)
Antibacterial effect of penicillin
discovered by Alexander Fleming
Fungal contaminant inhibited growth
on a plate of Staphylococcus aureus
Fleming unable to isolate pure
antibacterial agent but used crude
extracts
Florey and Chain manage to
produce antibiotic on industrial scale
(1939-1945)
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 Improving penicillin
Mode of action - prevents cross-linking of small peptide
chains in peptidoglycan inhibits cell wall formation
Effective against Gram positive bacteria
Penicillin is a group of closely related compounds:
e.g. penicillin G and V from P. notatum

Chemical modification
improves functionality
e.g. resistance to stomach acids
improved oral use

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Antibiotic discovery timeline
First new class in 30 years

Wright (2007)
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Monoclonal Antibodies (MAbs) (1975)
Purified antibodies specific to a specific antigen
Uses antibody-producing B (lymphocyte) cells

(indefinite growth)

(From spleen)
Kohler & Milstein (1975)
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Some MAb Applications
Diagnostics:
Clearblue pregnancy test kit based on detection of
human chorionic gonadotrophin hCG

Therapeutic examples:
1. Organ transplant rejection:
OKT-3 binds to T-cell receptor CD3 complex leading to initial
activation, but subsequent blocking and apoptosis of T-cells leading
to reduced immune response to foreign tissue following transplant
2. Crohns disease:
Remicade binds to tumour necrosis factor (TNF) alpha (a cytokine
forming part of the autoimmune system). Remicade prevents binding
of TNF to its receptor and initiating a signalling pathway, leading to
minimising of immune response and reduction in symptoms of
inflammatory bowel inflammation
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 DNA cloning (1972)
Paul Berg and his team, (1972) combined
DNA from the cancer-causing monkey virus
SV40 with bacteriophage DNA
Jackson et al., (1972) PNAS 69, 2904-2909.

Stanley Cohen and Herbert Boyer (1973) applied

Bergs techniques to insert DNA into the plasmid
pSC101.
AND transformed this into Escherichia coli to form
the first recombinant (genetically modified) organism
Cohen et al., (1973) PNAS 70, 1293-1297.

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 Development of Regulations on Cloning

1973 First recombinant molecule cloned into an organism

1974 Voluntary moratorium on cloning Berg letter
Berg et al., (1974) Science 185, 303.

1976 US NIH issued guidelines on recombinant DNA

technology included:
biological containment
use of preferred cloning hosts
negative pressure self contained rooms - cost implications
voluntary compliance
1980 US NIH-RAC relaxed regulations with respect to:
hosts; need for containment

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 Insulin
Insulin (and other hormones) originally isolated from
tissues, e.g. hGH from human cadavers
expensive, inefficient and risk of infection
1976: Genetech founded by Herbert Boyer
and Robert Swanson worlds first Genetech: www.gene.com
(recombinant DNA) Biotech company
1977: Cloning and expression of first human Itakura et al., (1977)
gene and its product (the hormone
somatostatin) in Escherichia coli by Herbert
Boyer and colleagues Goedell et al., (1979)
1979: Human insulin cloned into plasmid
pBR322 and expressed in E. coli
1992: Humulin (recombinant human insulin)
approved by US FDA 14
Recombinant human insulin production

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 Genetic modification of plants
1982: Cloning of bacterial (kanamycin
resistance) gene into tobacco plants
Fraley et al., (1983)

1987: Cloning of bacterial (Bt)

insecticidal (cry) genes into tobacco
plants
Vaeck et al., (1987)

1994: Flavr Savr tomato

commercialised
1995: BT potato (Monsanto) approved
for commercial use in U.S. by EPA
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Transgenic animals

Campbell et al., (1996), Wilmut et al., (1997)

http://www.nature.com/nature/dolly/
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 Human genome sequences (2001)

Private
vs.
Public

Venter Lander
(Private) (Public)

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 Synthetic life (2010)
Creation of a bacterial cell controlled by a chemically
synthesised genome
DNA-free cells of Mycoplasma mycoides containing an in vitro
chemically-synthesised chromosome
Opportunities for
designing microbes to:
degrade plant material
more efficiently
produce biofuels (eg.
Algal biodiesel)
produce electricity (eg.
Gibson et al., (2010) Science 329, 52-56.
http://www.jcvi.org (J. Craig Venter Institute) MFC)

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 Summary
Biotechnology is as old as civilization
Medical biotechnology transformed by
immunization and antibiotic discovery
Molecular biology has transformed
biotechnology.
Biotechnology is now driven by molecular,
genomic and systems-biology developments

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Any questions?

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 References
Berg et al., (1974) Science 185, 303.
Brekke & Sandlie, (2003) Nature Rev. Drug Disc. 2, 52-62.
Campbell et al.,(1996) Nature 380, 64-66.
Cohen et al., (1973) Proc. Natl. Acad. Sci. USA 70, 1293-1297.
Fraley et al. Proc. Natl. Acad. Sci. USA 80, 4803-4807
Gibson et al., (2010) Science 329, 52-56.
Goedell et al., (1979) Proc. Natl. Acad. Sci. USA 281, 544-548.
Itakura et al., (1977) Science 198, 1056-1063.
Jackson et al., (1972) Proc. Natl. Acad. Sci. USA 69, 2904-2909.
Kohler & Milstein (1975) Nature 256, 495-497.
Salque et al., (2012) Nature 493, 522-525.
Vaeck et al., (1987) Nature 328, 33-37.
Wilmut et al., (1997) Nature 385, 810-813.
Wright (2007) Nature Rev. Microbiol. 5, 175-186.

Nature (2001) Human Genome issue: http://www.nature.com/nature/journal/v409/n6822/

Science (2001) Human Genome issue: http://www.sciencemag.org/content/291/5507.toc

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