This document provides a history of biotechnology from its origins thousands of years ago to modern applications. It discusses: - Key events and discoveries from 6000 BC to the present, including the structure of DNA being discovered in 1953 and the first recombinant DNA molecule being created in 1972. - The major periods of biotechnology history: pre-1800, 1800-1900, 1900-1953, 1953-1976, 1977-present. - Applications of biotechnology in medicine (red), agriculture/food (green), industrial processes (white), and environment (blue). - Modern products like insulin, monoclonal antibodies, genetically engineered crops, and the use of microbes, plants, and animals to produce therapeutic proteins.

1. Introduction to
Biotechnology
Subject Code- BT-201
Department of Biotechnology
Delhi Technological University

2. UNIT-1
INTRODUCTION, SCOPE,
AND APPLICATION OF
BIOTECHNOLOGY

3. History of Biotechnology
• The term "biotechnology" was coined in 1919 by Karl
Ereky, a Hungarian engineer.
• Traditional biotechnology has been used for
thousands of years to produce improved food and
healthcare products. Today, modern biotechnology
enables us to develop improved products more safely
and more rapidly than ever before.

4. • Examples:
• They could plant their own crops and breed
their own animals, they learned to use
biotechnology.
• The discovery that fruit juices fermented into
wine, that milk could be converted into cheese
or yogurt, or that beer could be made by
fermenting solutions of malt and hops began
the study of biotechnology

5. Periods of Biotechnology History
• Pre- 1800: Early applications and speculation
• 1800-1900: Significant advances in basic
understanding
• 1900-1953: Genetics
• 1953- 1976: DNA research, science explodes
• 1977- present: modern biotechnology

6. Biotechnology Time Lines
• 6000 BC
Yeast was used to make beer by the Sumerians and Babylonians.
• 4000 BC
The Egyptians discovered how to bake bread using yeast.
• 420 BC
Socrates (470? - 399 BC), the Greek philosopher, speculated on
why children don't always resemble their parents.
• 320 BC
Aristotle (384 - 322 BC), told his students that all inheritance
comes from the father.

7. • 1000 AD
Hindus observed that certain diseases may "run in the
family." Spontaneous Generation is the dominant
explanation that organisms arise from non-living matter.
Maggots, for example, were supposed to arise from
horsehair.
• 1630 AD
William Harvey concluded that plants and animals alike
reproduce in a sexual manner:–eggs isolated in 1800’s
• 1660-1675 AD
Marcello Malpighi (1628-1694) in this period used a
microscope to study blood circulation in capillaries and
described the nervous system as bundles of fibers
connected to the brain by the spinal cord.

8. • 1673 AD
Anton van Leeuwenhoek (1632 - 1723), was the first scientist to
describe protozoa and bacteria and to recognize that such
microorganisms might play a role in fermentation.
• 1701
Giacomo Pylarini in Constantinople practiced "inoculation"--
intentionally giving children smallpox to prevent a serious case
later in life. Inoculation will compete with "vaccination"--an
alternative method that uses cowpox rather than smallpox as
the protecting treatment--for a century.

9. • 1856
Karl Ludwig discovered a technique for keeping animal organs
alive outside the body, by pumping blood through them.
• Louis Pasteur (1822 - 1895) asserted that microbes are
responsible for fermentation.
• 1859
Charles Darwin (1809 - 1882) hypothesized that animal
populations adapt their forms over time to best exploit the
environment, a process he referred to as "natural selection." As
he traveled in the Galapagos Islands, he observed how the
finch's beaks on each island were adapted to their food
sources.

10. • 1863
Louis Pasteur invented the process of pasteurization, heating
wine sufficiently to inactivate microbes (that would otherwise
turn the "vin" to "vin aigre" or "sour wine") while at the same
time not ruining the flavor of the wine. 50-60℃ for half an hour.
• Anton de Bary proved that a fungus causes potato blight. A
challenge for scientists during this period was to discern
whether a microbe was the cause of, or the result of, a disease.

11. • 1865
Gregor Mendel (1822 - 1884), an Augustinian monk,
presented his laws of heredity to the Natural Science Society
in Brunn, Austria. Mendel proposed that invisible internal
units of information account for observable traits, and that
these "factors" - which later became known as genes - are
passed from one generation to the next.

12. • 1883
Emil Christian Hansen made the
first pure yeast culture for beer
production in Gamle Carlsberg
Brewery, Copenhagen, Denmark.

13. • 1900 - 1953 - Converging on DNA
• 1900 MENDEL’S WORK FINALLY TOOK ON IMPORTANCE
The science of genetics was finally born when Mendel's
work was rediscovered by three scientists - Hugo DeVries,
Erich Von Tschermak, and Carl Correns - each one
independently researching scientific literature for
precedents to their own "original" work.
• 1902 HUMAN GENETICS BORN
Walter Stanborough Sutton stated that chromosomes are
paired and may be the carriers of heredity. He suggested
that Mendel's "factors" are located on chromosomes.

14. • 1905
X AND Y CHROMOSOMES RELATED TO GENDER
• Edmund Wilson and Nellie Stevens proposed the idea that
separate X and Y chromosomes determine sex. They showed
that a single Y chromosome determines maleness, and two
copies of the X chromosome determine femaleness.
• 1905-1908
• William Bateson and Reginald Crudell Punnett, along with
others, demonstrated that some genes modify the action of
other genes.
• 1906
• Paul Erlich investigated atoxyl compounds and discovered
the beneficial properties of Salvarsan - the first
chemotherapeutic agent.

15. • 1910 BASIS OF MODERN GENETICS
Thomas Hunt Morgan proved that genes are carried on
chromosomes, establishing the basis of modern genetics.
With his co-workers, he pinpointed the location of various
fruit fly genes on chromosomes, establishing the use of
Drosophila fruit flies to study heredity.
• 1911
Thomas Hunt Morgan explained the separation of certain
inherited characteristics that are usually linked as caused by
the breaking of chromosomes sometimes during the
process of cell division. Morgan began to map the positions
of genes on the chromosomes of the fruit fly.

16. • 1938
• Proteins and DNA were studied in various labs with X-ray
crystallography.
• The term "molecular biology" was coined.
• 1941
• ONE GENE ONE ENZYME
• George Beadle and Edward Tatum experimented with
Neurospora, a mold that grows on bread in the tropics,
developing the "one-gene-one-enzyme" hypothesis: each
gene is translated into an enzyme to perform tasks within an
organism.

17. • 1950
• Erwin Chargaff found that in DNA the amounts of
adenine and thymine are about the same, as are the
amounts of guanine and cytosine. These relationships
are later known as "Chargaff's Rules" and serve as a
key principle for Watson and Crick in assessing various
models for the structure of DNA. AT ABOUT THE
SAME; GC ABOUT THE SAME.

18. • 1953 - 1976: Expanding the Boundaries of DNA
Research
• The discovery of the structure of DNA resulted in
an explosion of research in molecular biology and
genetics, paving the way for the biotechnology
revolution.
• 1953Nature magazine published James Watson's
and Francis Crick's manuscript describing the
double helix structure of DNA.

19. • 1957 CENTRAL DOGMA OF DNA- HOW DNA
MAKES A PROTEIN
• Francis Crick and George Gamov worked out the
"central dogma," explaining how DNA functions to
make protein.
• 1959
• Francois Jacob and Jacques Monod established the
existence of genetic regulation - mappable control
functions located on the chromosome in the DNA
sequence - which they named the repressor and
operon.

20. • 1972
• FIRST RECOMBINANT DNA MOLECULE
• Paul Berg isolated and employed a restriction enzyme to cut
DNA. Berg used ligase to paste two DNA strands together to
form a hybrid circular molecule. This was the first
recombinant DNA molecule.
• 1972 NIH GUIDELINES FOR RECOMBINANT DNA
• In a letter to Science, Stanford biochemist Paul Berg and
others called for the National Institutes of Health to enact
guidelines for DNA splicing.. Their concerns eventually led to
the 1975 Asilomar Conference.

21. • 1977 - Present: The Dawn of Biotech
• Genetic engineering became a reality when a man-
made gene was used to manufacture a human protein
in a bacteria for the first time.
Biotech companies and universities were off to the
races, and the world would never be the same again.
In 1978, in the laboratory of Herbert Boyer at the
University of California at San Francisco, a synthetic
version of the human insulin gene was constructed
and inserted into the bacterium Escheria coli. Since
that key moment, the trickle of biotechnological
developments has become a torrent of diagnostic and
therapeutic tools, accompanied by ever faster and
more powerful DNA sequencing and cloning
techniques.

22. • 1977
• Genentech, Inc., reports the production of the first
human protein manufactured in a bacteria:
somatostatin, a human growth hormone-releasing
inhibitory factor. For the first time, a synthetic,
recombinant gene was used to clone a protein.
Many consider this to be the advent of the Age of
Biotechnology.
• 1978
• RECOMBINANT INSULIN Genentech, Inc. and The
City of Hope National Medical Center announced
the successful laboratory production of human
insulin using recombinant DNA technology.

23. • 1980 PATENTS ALLOWED
• The U.S. Supreme Court ruled in that genetically
altered life forms can be patented a Supreme Court
decision in 1980 allowed the Exxon oil company to
patent an oil-eating microorganism.
• Kary Mullis and others at Cetus Corporation in
Berkeley, California, invented a technique for
multiplying DNA sequences in vitro by, the polymerase
chain reaction (PCR).

24. • 1983
• Eli Lilly received a license to make insulin.
• 1985
• Genetic fingerprinting enters the courtroom.
• Cal Bio cloned the gene that encodes human lung
surfactant protein, a major step toward reducing
premature birth complications.
• Genetically engineered plants resistant to insects,
viruses, and bacteria were field tested for the first
time.
• The NIH approved guidelines for performing
experiments in gene therapy on humans.

25. • 1990
• The first gene therapy takes place, on a four-year-old girl with
an immune-system disorder called ADA deficiency. The therapy
appeared to work, but set off a fury of discussion of ethics both
in academia and in the media.
• The Human Genome Project, the international effort to map all
of the genes in the human body, was launched. Estimated cost:
$13 billion. 1990 Formal launch of the international Human
Genome Project.
• Publication of Michael Crichton's novel Jurassic Park, in which
bioengineered dinosaurs roam a paleontological theme park;
the experiment goes awry, with deadly results.

26. • 1997
Researchers at Scotland's Roslin Institute report that they
have cloned a sheep--named Dolly--from the cell of an
adult ewe. Dolly the first sheep cloned by nuclear transfer
technology bearing a human gene appears later. Nuclear
transfer involves transferring the complete genetic
material (the DNA contained in a nucleus) from one cell
into an unfertilized egg cell whose own nucleus has been
removed.
.

27. RED BIOTECHNOLOGY:
Medicine and pharmaceutics
GREEN BIOTECNOLOGY:
Agriculture and food
WHITE BIOTECNOLOGY:
Industrial proccesses
BLUE BIOTECNOLOGY:
Environment
Biotecnology Application

28. Biotech Applications
• Biopolymers and Medical Devices- natural substances
useful as medical devices
• Hyaluronate- an elastic, plastic-like substance
used to treat arthritis, prevent postsurgical
scarring in cataract surgery, used for drug
delivery
• Adhesive substances to replace stitches
• Designing Drugs – using computer modeling to design
drugs without the lab- protein structure

29. • Gene Therapy – replace defective genes with functional
ones
• ADA (adenosine deaminase) deficiency
• cystic fibrosis
• Immunosuppressive Therapies – used to inhibit
rejection (organ transplants)
• Cancer Therapies -one method is antisense technology
• Vaccines – biggest breakthrough in biotechnology-
prevention of disease

30. Products of Modern Biotechnology
•There are a wide variety of products that the biotechnology field
has produced.
•More than 65% of biotech companies in the U.S. are involved in
pharmaceutical production (relating to drugs developed for
medical use).
•1982 - Genentech developed Humulin
(human insulin) to treat diabetes.
•It was the first biotech drug to be FDA
approved.

31. •There are more than 80
biotech drugs, vaccines,
and diagnostics with
more than 400 biotech
medicines in
development targeting
over 2oo diseases!
•Nearly 1/2 of new drugs
target cancer

32. Top 10 Selling Biotech Drugs
Drug Developer Function
Betaseron Chiron/Berlex Multiple sclerosis
Ceredase Genzyme Gaucher’s disease
Engerix B Genentech Hepatitis B vaccine
Epiver GlaxoSmithKlein Anti-HIV
Epogen Amgen Red blood cell enhancement
Genotropin Genentech Growth failure
Humulin Genentech Diabetes
Intron Biogen Cancer & viral infections
Neupogen Amgen Neutropenia reduction
Procrit Amgen Platelet enhancement

33. Biotech Treatments
•In the near future, it may be
commonplace for treatments to include
the use of gene therapy (an attempt to
replace a “defective” gene with a
“normal” gene) and tissue engineering
(designing & and growing tissues for
use in regenerative medicines).
•1st Genetically Modified Organism
(GMO) to produce human protein was E.
coli (pictured right) which was given
DNA to produce somatostatin (hGH -
human growth hormone - 1977)

34. Tissue plasminogen activator
•One of the first genetically
engineered (GE) products
sold was tissue
plasminogen activator (tPA)
•tPA is a blood clot
dissolving enzyme used
immediately after a heart
attack or stroke to clear
blocked vessels

35. Other Biotech Products
• Other biotech products include
proteins in:
• Home pregnancy tests
(monoclonal antibodies)
• frost-resistant strawberry
plants
• Although many are focused on
medical and agricultural applications,
some are for our own fashion
interests (specialty apparel)!

36. Genes for Jeans?
• Stonewashed jeans use
genetically engineered
enzymes (amylase &
cellulase) to create a
faded look
• Originally, pumice stones
were used (jeans washed
with the stones)
• This method damaged
the machines

37. Microbial Applications
• Bacteria & and yeast are the most
frequently used microbes
• Better enzymes and organisms for
making foods, simplifying
manufacture and production
processes, and making
decontamination processes for
industrial waste product removal
more efficient.
• Microbes used to clone and
produce batch amounts of important
proteins

38. Agricultural Applications
•Agricultural Biotechnology is
estimated to be $6 billion market
(2005), including applications such as:
• Pest-resistant plants
• Higher protein & and vitamin content
in foods
• Drugs developed and grown as plant
products
• Drought-resistant, cold-tolerant, and
higher-yielding crops

39. Plant Advantage
• The Ag-Biotech field boasts about
the plant’s advantage over microbial
biotech.
• Plant advantage refers to the fact
that the cost of producing plant
material with recombinant proteins is
often significantly lower than
bacteria
• Also, the Ag biotech may combine
with medical biotech in order to
produce drugs with molecular
pharming

40. Molecular Pharming
• Molecular pharming is the use of
genetically modified plants (or animals) as
a source of pharmaceutical products.
• These are usually recombinant proteins
with a therapeutic value.
• This is an emerging but very challenging field that requires:
•manipulation (at the genetic engineering level) of protein
glycosylation (addition of polysaccharide chain)
•subcellular protein targeting in plant cells

41. Animal Applications
•Animals can be used as bioreactors!
•Many human therapeutic proteins are
needed in massive quantities (>100s of
kgs), so scientists create female transgenic
animals to express therapeutic proteins in
milk.
• Goats, cattle, sheep, & chickens are sources of antibodies (protective proteins that
recognize & destroy foreign material)
•Transgenic refers to containing genes from another source

42. Dolly
In 1996, Dolly sheep became the first cloned animal created by the somatic cell
nuclear transfer process.
• Born: July 5, 1996
• Announced: February 22, 1997
• Died: February 14, 2003
• Dolly was cloned from a cell taken from
a six-year-old ewe
• She became the center of much
controversy that still exists today

43. Cloned kitty
The first two cats cloned by chromatin transfer

44. Human Clone
• Britain grants embryo cloning patents and
became the first country in the world to
grant a patent covering cloned early-stage
human embryos. The decision ignited new
controversy among biotechnology critics
even though the Geron Corporation, the
company licensed to use the patent, has
no intention of creating cloned humans.

45. Knock Outs
• Basic research in biotech uses knock-out
experiments, which are very helpful for
learning about the function of a gene.
• A knock-out is created when an active gene
is replaced with DNA that has no functional
information.
• Without the gene present, it may be possible
to determine how the gene affects the
organism (its function)

46. Aquatic Applications
•Aquaculture is a common aquatic application of biotech.
•Aquaculture is the process of raising finfish or shellfish in controlled conditions for food
sources.
• Products include:
• transgenic salmon (increased growth rates)
•disease-resistant oysters
• vaccines against viruses that infect aquatic
species
•Overall, aquatic organisms are thought to be rich & valuable sources for new genes, proteins,
& metabolic processes.

47. Medical Applications
• Medical applications of biotech include preventative, diagnostic, and
treatment.
• The Human Genome Project is very useful within this field.
• Gene therapy and stem cell technologies are
two up-and-coming fields within the medical area
of biotech.
• Stem cell technologies include immature cells
that have the potential to develop and specialize
into a variety of other cell types.

48. Forensic Applications
•DNA fingerprinting is a classic example of a forensic application. It is used
most commonly for law enforcement and crime scene investigation (CSI).
•It was first used in 1987 to convict a rapist in England.
Other applications of DNA fingerprinting
include:
• identifying human remains
• paternity tests
• endangered species (reduces poaching)
• epidemiology (spread of disease )

49. Environmental Applications
• The major environmental use is for bioremediation.
• Bioremediation is the use of biotech to process or degrade a variety of
natural and manmade products, especially those contributing to pollution
• Therefore, cleaning up environmental hazards
produced by industrial progress is a major
application of this type of biotechnology.
• There is a strong tie to microbial biotech (since
many microbes are helpful for this area).

50. Bioremediation
• Bioremediation can be defined as any process that
uses microorganisms or their enzymes to return the
environment altered by contaminants to its original
condition.

51. ENVIRONMENT
• Environmental biotechnology has become another
area of extensive work due to the dangers brought
about by increasing levels of environmental pollution.
• A lot of hard work is being done to protect our
environment. In this field, the job of a biotechnologist
spans from checking industrial air pollution levels,
and treatment of industrial waste to recycling sewage
sludge.

52. Oil Spill
•In the 1970s, the first U.S. GMO patent was granted to a scientist for a strain of
bacteria capable of degrading components in crude oil.
•In 1989, the Exxon Valdez
oil spill in Alaska used
Pseudomonas species (oil-
degrading bacteria) to clean
up the spill
•It was 3x faster & without
increased environmental
effects

53. Waste Management
Environmental Pollution is a
major problem
Landfills are becoming full
Old dump sites are creating
problems
Waste is piling up
Sewage and chemical disposal
is a constant problem

54. Genetically altered bacteria are
used to feed on oil slicks and
spills
Bacteria are being developed to
decompose or deactivate dioxin,
PCBs, insecticides, herbicides,
and other chemicals
Bacteria are under development
to convert solid wastes into
sugars and fuel

55. • Photo of mouse growing a "human ear" - a shape
made of cartilage

56. Genetically Modified Food
• Can animal genes be jammed into plants? Would
tomatoes with catfish genes taste fishy? Have you
ever eaten a genetically modified food? The
answers are: “yes”, “no” and almost definitely “yes”
• Despite dire warnings about "Frankenfoods“, there
have been no reports of illness from these products
of biotechnology.

59. GM potato 'could improve child health'

60. Approved Biotech Products
• 1982: FDA approves genetically engineered human
insulin
• 1986: Orthoclone OKT3 (Muromonab-CD3) approved for
reversal of kidney transplant rejection.
• 1986: first recombinant vaccine approved- hepatitis
• 1987: Genentech gets approval for rt-PA (tissue
plasminogen activatior) for heart attacks

61. Focus on “Famous” Biotech Product:
Insulin
• Insulin:
• Insulin is a hormone, and therefore, a protein.
• Insulin was the first hormone identified (late 1920's) which won the
doctor and medical student who discovered it the Nobel Prize (Banting
and Best).
• They discovered insulin by tying a string around the pancreatic duct of
several dogs.
• Note that there are other hormones produced by different types of cells
within pancreatic islets (glucagon, somatostatin, etc) but insulin is
produced in far greater amounts under normal conditions making the
simple approach used by Banting and Best quite successful.

62. • The first successful insulin preparations came from
cows (and later pigs). The pancreatic islets and the
insulin protein contained within them were isolated
from animals slaughtered for food in a similar but
more complex fashion than was used by our doctor
and med-student duo.