• Technology timeline for Biotechnology
• Multidisciplinary nature of Biotech
• Global landscape of biotechnology
• Facts and momentum of biotechnology industry
• Business timeline of medical biotechnology
• Risks and rewards for medical biotechnology development

History of Biotechnology:
A Technology Timeline
• ~4000-6000 B.C.:
Microorganisms were used to make bread, cheese, and beer
• 1863: Mendel discovered the rules of trait inheritance through studying pea plants
• 1953: Watson and Crick reveal the doublehelix model of DNA
• 1961: Monod and Jacob discovered m RNA .
• 1965: Edman developed chemistry enabling automatic protein sequencing
• 1966: Genetic codes determined (Kohrana and Nirenberg)

History of Biotechnology:
A Technology Timeline
• 1973: Cohen and Boyer created the first recombinant DNA using bacterial genes
• 1974: Milstein and Kohler created a
“immortal” cell line that would produce large amounts of antibodies (hybridoma technology)

History of Biotechnology:
A Technology Timeline
• 1974: The National Institute of Health forms a
Recombinant DNA Advisory Committee to oversee research safety and ethics.
• 1977: Genetically engineered bacteria was used to make human protein

History of Biotechnology:
A Technology Timeline
• 1981: The first gene-synthesizing machines were developed.
The first genetically engineered plant was reported. Mice were successfully cloned
• 1983: PCR (polymerase chain reaction) was perceived
• 1983: The discovery of the first tumor suppressor gene
• 1985: Human Genome Project began
• 1987: Recombinant microbes were field tested for its ability to protect strawberry from frosting

History of Biotechnology:
A Technology Timeline
• 1989: Microorganisms are used to clean up oil spill ; The gene responsible for cystic fibrosis is discovered.
http://www.battelle.org/environment/exxon-valdez.stm

History of Biotechnology:
A Technology Timeline
• 1991: The first federally approved gene therapy treatment is performed successfully on a 4-year old girl suffering from an immune disorder.
• 1994: The first breast cancer gene was discovered.
Genetically engineered tomatoes ( Flavr Saver ® ) available in market
• 1997: Dolly was cloned ; The field of bioinformatics , which combines DNA chips, PCR and computer programs was developed to accelerate the study of genes 1998: Human skin is produced in vitro;
Embryonic stem cells are used to regenerate tissue and create disorders mimicking diseases.
The first complete animal genome for the elegans worm is sequenced.
graphics from www.agbio.com

History of Biotechnology:
A Technology Timeline
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•
•
References: http://www.biotechinstitute.org/what_is/timeline.html
Appendix A, From Alchemy to IPO by Robbins-Roth

Biotechnology is a science of many disciplines
Biotechnology is the
Integrated use of biochemistry, microbiology and engineering sciences in order to achieve technological
(industrial) application of the capabilities of microorganisms, cultured tissue cells and parts thereof
(www.efb.org)
Figure from “Introduction to Biotechnology” by Thielman et.al.

Products of Medical Biotechnology
Drug Developer
Betaseron Chiron/Berlex
Treatment of human disease conditions
Multiple sclerosis
Ceredase Genzyme Gaucher’s disease
Engerix B
Epiver
Epogen
Genotropin
Humulin
Intron
Neupogen
Procrit
Genentech
Glaxo SmithKlein
Amgen
Genentech
Genentech
Biogen
Amgen
Amgen
Hepatitis B vaccine
Anti-HIV
Red blood cell enhancement
Growth failure
Diabetes
Cancer and viral infection
Neutropenia reduction
Platelet enhancement
Top 10 selling biotechnology drugs from Ernst & Young LLP, Biotechnology Industry Report (2000)

Landscape of Global Biotechnology

Landscape of Global Biotechnology

Landscape of Global Biotechnology

• Biotechnology is a US$30 billion a year industry that has produced some 160 drugs and vaccines .
• There are more than 370 biotech drug products and vaccines currently in clinical trials targeting more than
200 diseases, including various cancers, Alzheimer’s disease, heart disease, diabetes, multiple sclerosis,
AIDS and arthritis.
• Market capitalization , the total value of publicly traded biotech companies (U.S.) at market prices, was US$311 billion as of mid-March 2004.
• Biotechnology is one of the most research-intensive industries in the world. The U.S. biotech industry spent
$17.9 billion on research and development in 2003.
From www.biotechinstitute.org

Biotechnology industry is a key driver for drug development
Levinson, Global Industry Perspective,
Beyond Borders: Biotechnology Report 2005

Biotechnology industry is a key driver for drug development
R&D productivity of big pharmaceutical companies has stayed flat
160
140
120
100
80
60
40
20
0
NDA submissions
FDA approvals
1995 1996 1997 1998 1999 2000 2001
Sources: PhRMA and Center for Drug Evaluation and Research

www.bio.org

Cetus founded
History of Medical Biotechnology:
A Business Timeline
First expression of a human gene in bacteria
Method developed for
Reading DNA sequences
Centocor founded
First monoclonal antibody diagnostic kit approved for marketing
Chiron, Genetics
Institute, Genzyme
Founded
Gene Synthesizing machines developed
Cohen and Boyer construct recombinant
DNA in bacteria
Genentech founded
DNA sequencing discovered
First monoclonal antibodies produced
Biogen
Hybritech founded
Recombinant human insulin produced
Amgen founded
Genetech initial stock offering
U.S. Supreme
Court rules that life forms are patentable
First product sales of recombinant insulin
Orphan Drug
Act passes
FDA approves first recombinant DNA product, human insulin for marketing
1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983
(presentation material from Prof. Langer, MIT)

History of Medical Biotechnology:
Chiron clones and sequences entire HIV genome
A Business Timeline
Human growth hormone approved by FDA
Cetus reports polymerase chain reaction technology
Tissue plasminogen activator approved by FDA
FDA approves
α -interferon, first recominant vaccine
Eli Lilly acquires
Hyberitech
Erythropoietin approved by
FDA
Human Genome project started
First U.S. patent on transgenic animal granted
First human gene therapy attempt
Roche acquires 60% of Genentech
Number of public companies falls for the first time
Alliances among drug and biotech firms increase
Legislation introduced to reform FDA
Healthcare reform creates uncertainty
β -interferon approved by FDA
Market for biotechnology
Trade treaty extends patent life to 20 years
Product stocks reaches all time high 2
284 products in clinical testing or awaiting approval
Amgen becomes a
Fortune 500 company
Factor VIII approved by FDA development failures keep investors away
1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996
(presentation material from Prof. Langer, MIT)

Risks and Rewards in Medical Biotechnology
• More than 60 million people have been helped by the biotech drugs and vaccines
• “A drug that would delay by 5 years the average age at which Alzheimer’s disease strikes would save US$50 bn annually; the same delay in the onset of Parkinson’s disease would save US$3 bn, and delaying the onset of cardiovascular disease and strokes by 5 years would save US$67 bn.”
- President of BIO
• Cost of biotech drug development
= US$125- US$ 359 million

Typical product development path in medical biotechnology www.bio.org

The patent system allows biotech companies to recover the development cost
• What is a patent?
• A patent is a set of exclusive rights granted by a state to a person (the patentee, usually the inventor) for a fixed period of time in exchange for the regulated, public disclosure of certain details of a device, method, process or composition of matter (substance) (known as an invention ) which is new, inventive, and useful or industrially applicable. (from Wikipidea)
• During the patent period, the costs of development and research may be recovered in the market.

1980: The first patent on engineered living organism granted to Chakrabarty
Picture from “Biotechnology: demystifying the concepts”
1988: “Harvard Mouse”