INTRODUCTION TO BIOTECHNOLOGY •Medicine

What is Biotechnology? 3. Modern Biotechnology

• Biotechnology = Derived from bios (life) + logos (study •Manipulation of genetic information in organisms
of or essence), meaning "the study of tools from living •Genetic engineering
things.“ AncientBiotechnology
• CLASSIC DEFINITION: The word "biotechnology" was ✓ HistoryofDomesticationandAgriculture
first used in 1917 to describe processes using living • Paleolithic society– Paleolithic society– Hunters and
organisms to create a product or run a process, such as Gatherers ➔ Nomadic lifestyle due to migratory animals
industrial fermentations. (Robert Bud, The Uses of Life: and the distribution of edible plants (wild wheat and
A History of Biotechnology) barley) (~2 million years ago)
• LAYMAN’S DEFINITION: Biotechnology began when • Followed by the domestication of plants and animals
humans started planting their own crops, domesticating (artificial selection) ➔ People settled, and sedentary
animals, fermenting juice into wine, making cheese, and lifestyles evolved (~10,000 years ago)
leavening bread. ⚬ Cultivation of wheat, barley, and rye (seed collection)
• GENENTECH: Biotechnology is the process of ⚬ Sheepandgoats ➔milk, cheese, butter and meat
harnessing "nature's own" biochemical tools to create ⚬ Grinding stones for food preparation
new products and processes and provide solutions to ⚬ Newtechnology ➔Origins of Biotechnology➔Agrarian
society's ills. (G. Kirk Raab, Former President and CEO of Societies
Genentech) AncientBiotechnology
• WEBSTER’S: The aspect of technology concerned with ✓ Fermentedfoodsandbeverages A long history of
the application of living organisms to meet the needs fermented foods since people began to settle (around
and purposes of humans. 9000 BC) (Fervere– to boil)
• WALL STREET: Biotechnology is the application of • Often discovered by accident!
genetic engineering and DNA technology to produce • Improved flavor and texture
therapeutic and medical diagnostic products and • Deliberate contamination with bacteria or fungi
processes. Biotech companies share one commonality: (molds) Examples: • Bread • Yogurt • Cheese • Wine •
the use of genetic engineering and the manipulation of Beer • Sour cream
organisms at a molecular level. AncientBiotechnology
• Using scientific methods with organisms to produce ✓ Fermentedfoodsandbeverages
new products or new forms of organisms. • Dough that is not baked immediately would undergo
• Any technique that uses living organisms or spontaneous fermentation ➔ it would rise ➔ Eureka!! •
substances derived from those organisms to create or Uncooked fermented dough could be used to ferment a
modify a product, improve plants or animals, or develop new batch ➔ no longer reliant on “chance
microorganisms for specific purposes. fermentation”
Biotechnology is a multidisciplinary in nature, • 1866–Louis Pasteur published his findings on the
involving input from: direct link between yeast and sugars ➔ CO2 + ethanol
• Engineering • Computer Science • Cell and Molecular (anaerobic process)
Biology • Microbiology • Genetics • Physiology • 1915–Production of baker’s yeast– Saccharomyces
• Biochemistry • Immunology • Virology cerevisiae
• Recombinant DNA Technology ➔ Genetic ClassicalBiotechnology
manipulation of bacteria, viruses, fungi, plants and ✓ The industry exploits early discoveries of the
animals, often for the development of specific products fermentation process for the production of a wide
What are the stages of biotechnology? range of products.
1. Ancient Biotechnology • Different types of beer • Vinegar • Glycerol • Acetone
• Early history as it relates to food and shelter, • Butanol • Lactic acid • Citric acid • Antibiotics– WWII
including domestication (A bioreactor was developed for large-scale production,
2. Classical Biotechnology e.g., penicillin made by the fermentation of Penicillium).
•Built on ancient biotechnology • Today, manydifferent antibiotics are produced by
•Fermentation promoted food production microorganisms.
Modern Biotechnology • Vaccine development (recombinant vaccines)
• Cell Biology • Environmental restoration
⚬ Structure, organization, and reproduction • Protection of endangered species
• Biochemistry o Synthesis of organic compounds • Conservation biology
o Cell extracts for fermentation (enzymes versus whole • Bioremediation
cells) • Forensic applications
• Genetics ⚬ Resurrection of Gregor Mendel’s findings • Food processing
➔ 1866 ➔ 1900s ￭ Theory of Inheritance (ratios Genetic Engineering
dependent on traits of parents) • Involves making changes to DNA to alter how living
￭ Theory of Transmission Factors organisms function.
o W.H. Sutton – 1902 • Enables the creation of new crops and farm animals.
o Chromosomes = inheritance factors • Produces bacteria capable of manufacturing
o T.H. Morgan – Drosophila melanogaster medicines.
• Watson, Crick, Franklin and Wilkins (1953) • Facilitates the growth of human body parts.
⚬ X-ray crystallography • Prevents genetic diseases and allows for the
⚬ 1962 – Nobel Prize awarded to three men ⚬ Chargaff modification of humans.
– DNA base ratios Genetically Modified Organism
⚬ Structural model of DNA developed • A genetically modified organism (GMO) refers to an
• DNA Revolution – Promise and Controversy!!! organism created through genetic engineering.
• The scientific foundation of modern biotechnology • The World Health Organization (WHO) defines a GMO
• Based on knowledge of DNA, its replication, repair, as an "organism, either plant, animal, or microorganism,
and use of enzymes to carry out in vitro splicing of DNA in which the genetic material (DNA) has been altered in
fragments a way that does not occur naturally through mating or
• Breaking the Genetic Code– Finding the Central natural recombination."
Dogma GMOs in Food and Agricultural Industries
• An “RNA Club” organized by George Gamow (1954) 1. Pest resistance
assembled to determine the role of RNA in protein 2. Virus resistance
synthesis 3. Herbicide tolerance
• Vernon Ingram’s research on sickle cell anemia (1956) 4. Fortification
tied inheritable diseases with protein structure ⚬ Alink 5. Cosmetic preservation
madebetween amino acids and DNA 6. Increase growth rate
• Radioactive tagging experiments demonstrate Fishy Strawberries?
intermediate between DNA and protein = RNA 1. The flounder’s antifreeze gene is copied and inserted
⚬ RNAmovementtracked from nucleus to cytoplasm ➔ into a small ring of DNA taken from a bacterium cell.
site of protein synthesis 2. The DNA ring containing the flounder gene is put into
• DNA ➔ RNA ➔ Protein Transcription Translation a second bacterium.
• Genetic code determined for all 20 amino acids by 3. This second bacterium is used to infect the
Marshal Nirenberg and Heinrich Matthaei and Gobind strawberry cell. The flounder’s antifreeze gene enters
Khorana – Nobel Prize – 1968 the strawberry’s DNA.
• 3 base sequence = codon 4. The new GM strawberry cell is grown into a GM
Benefits of Biotechnology strawberry plant, which can be bred many times.
• Medicine • Human • Veterinary • Biopharming
• Environment • Agriculture • Food products • Industry This diagram shows how one type of GM food, a
and manufacturing strawberry that resists frost damage, is made. The
Applications of Biotechnology flounder is a fish that lives in icy seas. It has a gene that
• Production of new and improved crops/foods, stops it from freezing to death. Strawberries are soft
industrial chemicals, pharmaceuticals, and livestock fruits that can easily be damaged by frost. Thanks to the
• Diagnostics for detecting genetic diseases new gene, GM strawberries produce a protein that
• Gene therapy helps them resist frost. They don’t contain any other
fish genes and do not taste or smell like fish. How Did They Do That?
Can We End World Hunger? Malnutrition and Vitamin 1. The jellyfish has a gene that produces a glowing
Deficiencies protein, which makes the jellyfish glow under certain
types of light.
2. The glowing gene is taken from a jellyfish cell and
spliced (inserted) into an empty virus cell (with no
harmful virus in it).
3. The genetically engineered virus attaches itself to the
fertilized mouse egg cell.
4. The virus delivers the glowing gene into the egg cell
nucleus, where it joins the mouse DNA.
5. The genetically engineered mouse egg grows into an
adult mouse that will produce the glowing protein. The
glow is too faint to see under normal light but can be
detected using a special camera

Golden rice is genetically modified rice that now

contains a large amount of vitamin A. More specifically,
the rice contains beta carotene, which is converted into
vitamin A in the body. So, when you eat golden rice, you
get more vitamin A.
That's Unbelievable! Genetic engineering examples
Beta-carotene gives carrots their orange color and is
include taking the gene that produces poison in the tail
the reason why genetically modified rice is golden. For
of a scorpion and combining it with a cabbage. These
golden rice to produce beta-carotene, three new genes
genetically modified cabbages kill caterpillars because
are implanted: two from daffodils and one from a
they produce scorpion poison (insecticide) in their sap.
bacterium.
Advantages: The rice can be considered a significant
That's Unbelievable! Genetic engineering also involves
advantage for poor people in underdeveloped
the insertion of human genes into sheep so that they
countries, who often have a very limited diet lacking
secrete alpha-1 antitrypsin (protein) in their milk, a
essential vitamins. The consequences of this restricted
useful substance for treating certain cases of lung
diet cause many people to die or become blind. This is
disease.
particularly true in parts of Asia, where most of the
population lives on rice from morning to evening.
Benefits of GMO
Crops
Better taste and quality
Reduced ripening time
Increased nutrients and more food
Improved resistance to disease, pests, and herbicides
New products and growing techniques
Animals
Increased resistance, productivity, hardiness, and feed
efficiency
Better yields of meat, eggs, and milk
Improved animal health and diagnostic methods transplanted into David Bennett Sr., a 57-year-old with
Environment terminal heart disease.
• "Friendly" bioherbicides and bioinsecticides
• Conservation of soil, water, and energy The first Clone Now cats may have more than nine lives.
• Better natural waste management The company that funded the first successful cloning of
• More efficient processing a domestic cat two years ago has gone commercial. The
Society cost? U.S. $50,000 each.
More food for growing populations
Potential Risks of GMO The first Clone CC, the first-ever cloned cat, is shown
Safety here at seven weeks old with Allie, her surrogate
• Potential human health impact: Allergens, transfer of mother. The cat was cloned by transplanting DNA from
antibiotic resistance markers, and unknown effects. Rainbow, a female tortoiseshell (or calico) cat, into an
• Potential environmental impact: Unintended transfer egg cell whose nucleus had been removed, and then
of transgenes through cross-pollination and loss of implanting the embryo into Allie, the surrogate mother.
flora and fauna biodiversity.
Access and Intellectual Property The first Clone “CC's coat color suggests that she is a
• Domination of world food production by a few clone, and a genetic match between CC and the donor
companies can lead to monopoly power. mother confirms this,” researchers say.
• Increasing dependence of developing countries on
industrialized nations may lead to economic Ralph, a rat, is the latest clone, whereas Dolly the
vulnerability. sheep, born in 1996, was the first cloned animal. Dolly
Ethics was cloned from an adult somatic cell, marking a
• Violation of natural organisms' intrinsic values. significant milestone in genetic research.
• Tampering with nature by mixing genes across
species. Dolly the Sheep (Finn-Dorset Sheep)
• Objections to consuming animal genes in plants and ▪ July 5, 1996 – February 14, 2003
vice versa. ▪ Roslin Institute in Scotland
• Stress for animals. ▪ 277
Potential Environmental Risks of GMO ▪ David – Welsh Mountain Sheep
1. Potential risk of the modified gene being transferred ▪ 6 Lambs (Bonny, Sally, Rosie, Lucy, Darcy, and Cotton)
from GMO crops to wild relatives or organisms in the
soil and human intestines (when ingested). The researchers from China and France say they
2. Emergence of new forms of resistance, as well as managed to create several rodent copies, both male
secondary pests and weed problems. and female. The rat joins a growing list of animals that
3. Recombination of viruses and bacteria could result in have been cloned from an adult cell, including sheep,
the production of new pathogens. mice, cattle, goats, pigs, cats, mules, and horses.
Potential Human Risks of GMO
1. Human Genome Project The rat came later than the others due to unique
2. Mutation of genetically engineered microorganisms difficulties in controlling the development of its eggs in
3. Cloning the early stages of the cloning process. Rat eggs activate
almost immediately after leaving the ovaries, making it
By inserting a gene for human insulin into an Escherichia difficult to introduce the genetic material of the animal
coli (E. coli) bacterium, the E. coli will produce large to be copied
amounts of insulin, which scientists and doctors can
collect and use. Cloning HUMANS?
❑UK scientists clone human embryo. British scientists
The world’s first successful pig heart transplant was say they have cloned the country's first human embryo.
performed at the University of Maryland School of The Newcastle University team took eggs from 11
Medicine. A genetically modified pig heart was women, removed the genetic material, and replaced it
with DNA from embryonic stem cells. UNRAVELING THE WORLD OF NANOTECHNOLOGY
❑The aim of this kind of work—the subject of fierce
debate—is to create cloned embryos from which stem
cells can be used to treat diseases.
❑Meanwhile, South Korean scientists say they have
created stem cells to match individuals for the first
time.
❑Stem cell lines were created by taking genetic
material from the patient and inserting it into a donated
egg.
❑The resulting cells were a perfect match for the
individual and could lead to treatments for diseases like
diabetes without the problems of rejection
❑Therapeutic cloning, believed to have huge potential
to treat disease and disability, is allowed in Britain.
❑Reproductive cloning—the cloning of human embryos
with the intention of creating a baby—was made illegal
in 2001."
GMO in Philippine Context
❑ The introduction of GMOs in our country has created
issues and controversies similar to those in other
countries with GMOs.
❑The GMO concern began in the 1990s with the
creation of the National Committee on Biosafety of the
Philippines (NCBP) through Executive Order No. 430 of
1990.
❑ They developed guidelines for the planned release of
genetically modified organisms (GMOs) and potentially
harmful exotic species in 1998.
❑ In 2002, the Department of Agriculture released
Administrative Order No. 8, which provided guidelines
for the importation and release into the environment of HISTORY OF NANOTECHNOLOGY
GM plants and plant products.
❑ That same year, GMO importation began.
❑ The Philippines became the first country in Asia to
approve the commercial cultivation of GMOs when the
planting of GM corn was approved in 2002
❑On March 7, 2016, the DOST, DOA, DENR, DOH, and
DILG passed Joint Department Circular No. 1, Series of
2016, which outlines the rules and regulations for the
research and development, handling and use,
transboundary movement, release into the
environment, and management of GM plants and plant
products derived from modern biotechnology.
❑ This joint department circular paved the way for the
issuance of new permits for planting and importing GM
crops in the country.
APPLICATION NANOTECHNOLOGY
 Gene Therapy
Definition & History
❑ A potential method for treating or curing genetic
related human illnesses.
❑ Anormal gene is inserted into the genome to replace
ADVANTAGES OF NANOTECHNOLOGY a non-functional gene.
❑ Trials began in 1971.
❑ Moderate success has been achieved with the cystic
fibrosis gene.
The Basic Process
❑ Replacement of a mutated gene that causes disease
with a healthy copy of the gene
❑ Inactivation of a mutated gene that is functioning
improperly
❑ Introducing a new gene into the body to help fight a
disease
Vectors
DISADVANTAGES OF NANOTECHNOLOGY ❑ Viruses (Retroviruses and Adenoviruses)
❑ Direct introduction (“golden bullets”)
❑ Liposomes Vectors
❑ Endocytosis of DNA bound to cell surface receptors
(low efficiency)
❑ Artificial chromosome (under development)
Types of Gene Therapy
❑ Somatic cell therapy targets most cells in the body.
All gene therapy conducted so far in humans has been
directed at somatic cells. It involves manipulating genes
in these cells to benefit the patient, but the changes are
not passed on to the next generation.

1. Somatic Gene Therapy

❑ Ex vivo- This is a method where cells are
modified outside of the body and then Adenosine Deaminase Deficiency (ADA) A
transplanted back into the patient. person born with adenosine deaminase (ADA)
❑ In vivo- This method involves changing genes deficiency lacks an important enzyme in their
directly within cells still inside the body. immune system, making them more susceptible
2. Germline therapy (such as sperm cells, ova, to infections, which can be fatal.
and their stem cell precursors). Bolstering the Immune System Current
❑ Germline engineering in humans remains a research focuses on the immune system, a
highly controversial prospect. collection of cells and chemicals that fight
❑ It involves the genetic modification of germ infection. If the immune system isn't
cells (sperm or egg cells) or their precursor cells, functioning properly, illness can result. Gene
with the changes being passed on to the next therapy may help "bolster" the immune system,
generation. potentially enabling the body to prevent cancer
Stem Cell Gene Therapy on its own.
3. Stem Cells X-SCID Children affected by X-linked severe
❑ Proliferative cells capable of self- combined immune deficiency (X-SCID) have a
maintenance. faulty gene, resulting in no functioning immune
❑ Candivide and differentiate into various cell system, leaving their bodies unable to fight
types. infections.
❑ Important for tissue regeneration and cell
replacement throughout life. 2017 was the year of Gene Therapy
❑ Transfection– The process of deliberately breakthroughs
introducing naked or purified nucleic acids into
eukaryotic cells. Sickle-Cell cure In March, researchers
✓ Applications: Used to introduce therapeutic announced that a teenage boy in France had
genes into target cells, such as those affected by been cured of sickle-cell disease after receiving
genetic disorders, or to modify immune cells for an experimental gene therapy developed by
cancer immunotherapy. Bluebird Bio. Sickle-cell disease, caused by a
❑ Transduction– The process by which foreign single genetic mutation, is an inherited blood
DNA is introduced into a cell by a virus or viral disorder that affects 100,000 people in the U.S.
vector. An example is the viral transfer of DNA and millions globally.
from one bacterium to another. Scientists removed stem cells from the boy's
✓ Applications: Treatments for genetic bone marrow and modified them in the lab by
disorders like cystic fibrosis or muscular introducing a gene to prevent his red blood cells
dystrophy, as well as in cancer therapies where from becoming "sickled." When the treated
immune cells are genetically modified to target cells were infused back into his body, they
tumors more effectively. began to produce normal blood cells. More
Applications of stem cell gene therapy than two years after treatment, the patient has
❑ Hemophilia Treatment enough normal red blood cells to avoid any side
❑ Repairing Mutations effects of the disorder.
❑ Heart Disease Treatment
❑ Sickle Cell Disease Treatment
❑ Skin Disease Treatment
Some examples of Gene Therapy
Leber’s Congenital Amaurosis (LCA In February
2007, a gene therapy trial was conducted at the
NIHR Biomedical Research Centre in the US with
three patients (about 18 years old) suffering
from Leber’s Congenital Amaurosis (LCA), a rare
inherited eye disease.
 a mutation responsible for a range of retinal
diseases that cause gradual blindness. In human
trials, the treatment has restored vision for
more than two dozen patients who were losing
their sight.
Hope for Hemophilia BioMarin is a company
working on a gene therapy that replaces the
faulty gene involved in the most common type
of hemophilia, effectively curing the disorder. In
December, the company published early clinical
trial results showing that nine patients who
received its therapy experienced substantial
increases in the blood clotting proteins that are
absent in hemophilia.
Cancer Killers This year, the FDA approved two A year and a half after treatment, patients had
pioneering treatments, Kymriah and Yescarta, fewer bleeding issues and were able to reduce
that use a patient’s own immune cells to fight their need for clotting factor infusions.
rare types of cancer. Called CAR-T therapies, Meanwhile, a handful of patients with
these “living drugs” are created by extracting T hemophilia B, a rarer form of the disease, are
cells from patients and genetically engineering already experiencing remarkable improvements
them to target and destroy cancer cells. The after a one-time treatment.
modified cells are then infused back into the Gene Therapy Successes
body. Sebastian Misztal was a patient in a hemophilia
So far, these therapies are being tested only in a gene therapy trial in 2011. After the treatment,
handful of lethal cancers as a last resort when Misztal no longer experienced spontaneous
more traditional treatments, like bleeding episodes.
chemotherapy, don’t work. Kymriah treats a In 2007, a patient received gene therapy for
bone marrow cancer that affects children and severe beta thalassemia. Blood stem cells were
young adults, while Yescarta treats a type of taken from his bone marrow, treated with a
lymphoma. Some patients have had remarkable retrovirus to add a working beta-globin gene,
recoveries and remain in remission months or and then returned to his body. Seven years
years later. later, he was still doing well without the need
Building New Skin When a bacterial infection for blood transfusions.
threatened his life, a boy with a devastating ❑ Fat Metabolism Disorder
connective tissue disorder called epidermolysis ❑ In 2012, Glybera became the first viral gene
bullosa received new skin created with gene therapy treatment to be approved in Europe.
therapy. To make it, scientists extracted cells The treatment uses an adeno-associated virus
from a part of the child’s body that wasn’t to deliver a working copy of the LPL (lipoprotein
blistered. lipase) gene to muscle cells. The LPL gene codes
They isolated skin stem cells, added copies of a for a protein that helps break down fats in the
healthy version of the gene, and let these cells blood, preventing fat concentrations from rising
grow into small sheets. In a series of three to toxic levels.
surgeries, they transplanted the new skin onto ❑ Parkinson’s Disease
the patient’s body at a hospital in Germany. ❑ Patients with Parkinson's disease gradually
Researchers announced the groundbreaking lose brain cells that produce dopamine, a
skin graft in November. chemical that helps control movement. As the
Restoring Sight In December, the FDA approved disease progresses, patients lose the ability to
the first gene therapy for an inherited disease. control their movements.
The treatment, called Luxturna, aims to correct ❑ A small group of patients with advanced
Parkinson's disease was treated with a retroviral ❑ The working gene might be inserted into the
vector to introduce three genes into brain cells wrong location in the genome.
in a small area. These genes allowed cells that ❑ The working gene might produce too much
don't normally make dopamine to start of the missing enzyme or protein, leading to
producing it. After the treatment, all of the other health problems.
patients in the trial showed improved muscle ❑ Other genes maybe accidentally delivered to
control. the cell. ❑ Thedeactivated virus might target
Gene Therapy Patients: cells other than the intended ones.
Ashanthi DeSilva ❑ Thedeactivated virus may become
❑ Afour-year-old girl became the first gene contagious.
therapy patient on September 14, 1990, at the Things to remember:
NIH Clinical Center. She had adenosine ❑ Gene therapy is an experimental treatment
deaminase (ADA) deficiency, a genetic disease that replaces a faulty, disease-causing gene with
that leaves her defenseless against infections. a functional one or introduces a new gene to
Cindy Kisik treat or modify a condition.
❑ A nine-year-old girl became the second gene ❑ Its goal is to eliminate genetic diseases at
therapy patient at the NIH Clinical Center. She their source.
had Adenosine Deaminase Severe Combined ❑ A key challenge for nations conducting gene
Immunodeficiency (ADA SCID), a type of Severe therapy research is developing practical, fair,
Combined Immune Deficiency caused by and ethical guidelines for its application.
mutations in a gene that encodes an enzyme
called ADA. CLIMATE CHANGE
Jesse Gelsinger
❑ First person publicly identified as having died
in a clinical trial for gene therapy.
❑ Hesuffered from ornithine transcarbamylase
(OTC) deficiency, an X-linked genetic disorder of
the liver.
❑ The condition was managed with a low-
protein diet and medications, including 32 pills
a day.
Jolee Mohr
❑ Jolee Mohr was lying in a Chicago hospital,
her body swollen from internal bleeding and
organ failure. She had taken an experimental
treatment for rheumatoid arthritis, a chronic
autoimmune disease that causes inflammation
in the joints. Jolee was 36 years old when she
died.
Advantages of Gene Therapy
❑ It has the ability to replace defective genes or
cells. ❑ It promises great untapped potential
for treating a wide range of diseases.
❑ It can help eradicate certain genetic
disorders and diseases.
The risks of Gene Therapy
❑ Theimmunesystem may respond to the
inserted working gene copy by causing
inflammation.