BIOTECHNOLOGY

A RESEARCH PAPER

Submitted by:
Devon John P. Suba
BSBIO1

Submitted to:
Dr. Eden David
 BIOTECHNOLOGY: THE ADVANCEMENT OF BIOLOGY

1.1: History

The term Biotechnology brings many different meaning to mind. Development

of GMOs(genetically modified organisms), new and an effective source of therapeutic
drugs. Still most researchers envision the possibility of growing crops that is
nutritious and naturally pest-resistant to feed the world’s growing population.

Throughout human history, since prehistoric times, biotechnology had been

already used by our ancestors. When the first human beings realized that they could
plant their own crops and breed their own animals, they learned to use biotechnology.
The discovery that fruit juices can be fermented into wine or 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. When the first bakers found that
they could make soft, spongy bread rather than a firm, thin cracker, they were acting
as fledgling biotechnologists. The first animal breeders, realizing that different
physical traits could be either magnified or lost by mating appropriate pairs of
animals, engaged in the manipulations of biotechnology.

1.2: What is Biotechnology?

The term Biotechnology brings many different meaning to mind. Development

of GMOs(genetically modified organisms), new and an effective source of therapeutic
drugs. Still most researchers envision the possibility of growing crops that is
nutritious and naturally pest-resistant to feed the world’s growing population.
.Biotechnology is the technology that is based on Biology, Agriculture, Food Science,
and Medicine. In its purest form, Biotechnology refers to the use of living organisms
or their products to modify human health and environment.

Biotechnology is the science for this century. With its advances, we are on the first
part of a great journey. Humans have expanded their understanding of the biosphere
by journeying into space and exploring the depths of the ocean. We have not only
been able to look at the surrounding universe and the depths below with the
advancement of tools and techniques, but we also have been able to live there. The
advancement tools and techniques, that is now allowing us to look at the universe of
atoms. Biotechnology is utilizing the sciences of biology, chemistry, physics,
engineering, computers, and information technology to develop tools and products
that hold great promise and concern. Humans have always been "manipulating"
organisms to their advantage, but now we are able to manipulate life and materials at
the atomic level through nanotechnology.
1.2: Biotechnology: A friend or A foe?

Vitamin A-enhanced golden rice, drought-resistant and pest-resistant Bt corn,

delayed ripening tomato and pesticide-resistant Soya beans-are best examples of
genetically modified organism which are the products of crop biotechnology. These
are the results of human endeavours in applying biological principles for the benefit
of mankind.

It is very evident that GMOs are of great benefit to mankind especially in the
increase production of food for human consumption. And also in the production of
flour for longer bread life and enzymes that serve as an alternative source for cheese
producers.

1.2.1: Biotechnology and the environment

Is there a basis for the fear of some people regarding the possible long-term
harmful effects of Biotechnology on the consumers and the environment? For better
assessment of this Query, let us look at some insights on the potential benefit as well
as potential risk of biotechnology to the environment.

Regarding the benefits. The development of GMOs promises mankind a

significant environmental benefit. They help to conserve our natural resources. For
instance GMOs with high pest resistant doesn’t need pesticide. And without pesticide
usage, the pollution cause by chemicals is significantly reduced. Farm lands that are
damage by sea waters can be productive again by planting salt-tolerant GM crops.
And with the use of GM crops that is high-yielding and pest-resistant farmlands
where able to meet the demand of growing population for food, without opening new
areas for production. Hence, the worlds remaining forest, habitats and biodiversity
will be conserved. In review, significant benefits include: higher crop yields,
increased farm profit and reduced farm cost, and improvements in the environment.

The main environmental risk posed by biotechnology is their potential of

mating with the weeds, thus creating a new weed species. But such risk was proven
untrue. Another possible risk is the development of insect resistance. For instance will
the Bacillus thuringiensis (Bt) insect resistant result in the development of insect
resistant to Bt? Another threat is the possible impact or harmful effect of GM crops on
non-target organism such as in the case of Bt corn, which pollen had a harmful effect
on monarch butterfly larvae. However the researchers stated that the study was
conducted inside the laboratory, therefore it is inappropriate to draw any conclusions
about the risk to monarch populations. In summary, The potential risk include; the
danger of unintentionally introducing allergens and other anti-nutrition factors in
food; the likelihood of trans-genes escaping from cultivated crops into wild relatives;
the potential for pest to evolve resistance to the toxins produced by GM crops; and the
risk of these toxins affecting non-target organisms.
II: Branches of Biotechnology

Bioinformatics is an interdisciplinary field which addresses biological

problems using computational techniques, and makes the rapid organization and
analysis of biological data possible. The field may also be referred to as
computational biology, and can be defined as, "conceptualizing biology in terms of
molecules and then applying informatics techniques to understand and organize the
information associated with these molecules, on a large scale. "Bioinformatics plays a
key role in various areas, such as functional genomics, structural genomics, and
proteomics, and forms a key component in the biotechnology and pharmaceutical
sector.
Blue biotechnology is a term that has been used to describe the marine and
aquatic applications of biotechnology, but its use is relatively rare.
Green biotechnology is biotechnology applied to agricultural processes. An
example would be the selection and domestication of plants via micro-propagation.
Another example is the designing of transgenic plants to grow under specific
environmental in the presence (or absence) of chemicals. One hope is that green
biotechnology might produce more environmentally friendly solutions than traditional
industrial agriculture. An example of this is the engineering of a plant to express a
pesticide, thereby ending the need of external application of pesticides. An example of
this would be Bt corn. Whether or not green biotechnology products such as this are
ultimately more environmentally friendly is a topic of considerable debate.
Red biotechnology is applied to medical processes. Some examples are the
designing of organisms to produce antibiotics, and the engineering of genetic cures
through genomic manipulation.
White biotechnology, also known as industrial biotechnology, is biotechnology
applied to industrial processes. An example is the designing of an organism to
produce a useful chemical. Another example is the using of enzymes as industrial
catalysts to either produce valuable chemicals or destroy hazardous/polluting
chemicals. White biotechnology tends to consume less in resources than traditional
processes used to produce industrial goods. The investments and economic output of
all of these types of applied biotechnologies form what has been described as the bio-
economy.
Gene therapy is used for treating, or even curing, genetic and acquired
diseases like cancer and AIDS by using normal genes to supplement or replace
defective genes or to bolster a normal function such as immunity. It can be used to
target somatic (i.e., body) or gametes (i.e., egg and sperm) cells. In somatic gene
therapy, the genome of the recipient is changed, but this change is not passed along to
the next generation. In contrast, in germ line gene therapy, the egg and sperm cells of
the parents are changed for the purpose of passing on the changes to their offspring.

III: Latest breakthroughs

Human genome project, Recombinant proteins, recombinant vaccines, targeted

drug therapy, therapeutic cloning, transgenic models for testing were some of the
breakthroughs in Biotechnology.

Here is the timeline for Notable events in the history of biotechnology:

Before 8000 BC – Collecting of seeds for replanting. Evidence that Mesopotamian
people used selective breeding (artificial selection) practices to improve livestock.
Around 7000 BC – Brewing beer, fermenting wine, baking bread with help of yeast.
8000 BC - 3000 BC – Yogurt and cheese made with lactic-acid-producing bacteria by
various cultures.
1590 – The microscope is invented by Zacharias Janssen.
1675 – Microorganisms discovered by Anton van Leeuwenhoek.
1856 – Gregor Mendel discovered the laws of inheritance.
1862 – Louis Pasteur discovered the bacterial origin of fermentation.
1919 – Karl Ereky, a Hungarian agricultural engineer, first used the word
biotechnology.
1928 – Alexander Fleming noticed that a certain mould could stop the duplication of
bacteria, leading to the first antibiotic: penicillin.
1953 – James D. Watson and Francis Crick describe the structure of deoxyribonucleic
acid, called DNA for short.
1972 – The DNA composition of chimpanzees and gorillas is discovered to be 99%
similar to that of humans.
1975 – Method for producing monoclonal antibody developed by Kohler and
Milstein.
1980 – Modern biotech is characterized by recombinant DNA technology. The
prokaryote model, E. coli, is used to produce synthetic insulin and other medicine, in
human form. (It is estimated that only 5% of diabetics were allergic to animal insulins
available before, while new evidence suggests that type 1 diabetes mellitus is caused
by an allergy to human insulin).
A viable brewing yeast strain, Saccharomyces cerevisiae 1026, acts as a modifier of
the microflora in the rumen of cows and digestive tract of horses).
The United States Supreme Court, in 447 U.S. 303 (1980), rules in favor of
microbiologist Ananda Chakrabarty in the case of a USPTO request for a first patent
granted to a genetically modified living organism (GMO) in history.
1984 – Nutrigenomics as applied science in animal nutrition.
1994 – the U.S. Food and Drug Administration approves of the first GM food: the
"Flavr Savr" tomato.
1997 – British scientists, led by Ian Wilmut, from the Roslin Institute report cloning a
sheep called Dolly the sheep using DNA from two adult sheep cells.
2000 – Completion of a, "rough draft," of the human genome in the Human Genome
Project.
2002 – Researchers sequence the DNA of rice, the main food source for two-thirds of
the world's population. Rice is the first crop to have its genome decoded.
2003 – GloFish, the first biotech pet, hits the North American market. Specially bred
to detect water pollutants, the fish glows red under black light thanks to the addition
of a natural bioluminescence gene.
2004 –
November – Korean researchers treat spinal cord injury by transplanting multipotent
adult stem cells from an umbilical cord blood.
December – A team of researchers at the University of Paris develops a method to
produce large number of red blood cells from hematopoietic stem cells, creating an
environment that mimics the conditions of bone marrow.
2005 –
January – Researchers at the University of Wisconsin-Madison differentiate human
blastocyst stem cells into neural stem cells, and finally into spinal motor neuron cells.
Vaxine trials show 1st swine flu vaccine works well

Singapore, Aug 26, 2009: The initial results from the clinical trials of the world’s
first recombinant vaccine against swine flu, developed by a small South Australian
biotech company, Vaxine Pty Ltd, indicates that the vaccine is working well in
humans.
Vaxine started the human clinical trials of the world’s first swine flu vaccine, on July
20, 2009. Three days ahead of Australia’s pharma giant CSL’s vaccine trials.

Prof Petrovsky (Vaxine Pty’s research director) said Vaxine’s swin flu vaccine has
been tested in three different doses of antigen ranging from 3 to 45 micrograms of
haemagglutinin with and without adjuvant. The company is using its own proprietary
Advax adjuvant. The vaccine’s antigen is a recombinant protein supplied by Protein
Sciences Corporation, based in Meridien, USA. The vaccine is designed to provide
powerful protection against influenza through anti-influenza antibodies, and T-cells
which are some of the key components of the body’s natural defense against the
influenza virus.
Seven other trials of swine flu vaccine developed by vaccine companies in five
countries are currently going on.

Being the world’s first swine flu vaccine, this Australian company’s efforts are
watched avidly around the world. The efficacy data of the vaccine is expected to
release in a few weeks. For the clinical trials, the Vaxine’s vaccine has been
administered to 275 male and female patients in the age group of 18 to 70 at Flinders
Medical Center in Adelaide. Vaxine is a spinout of Flinders University. The clinical
trials are being conducted by Prof David Gordon at Flinders University.

China’s Sinovac has announced that the results of its swine flu vaccine trials which
started a week after Vaxine, has also been good. Sinovac is using a single dose of 15
mg. Prof Petrovsky said his company’s genetically-engineered vaccine has several
advantages over other products such as CSL’s egg based vaccine. “Our vaccine is free
of egg protein contaminants and so is safe for people with serious egg allergy. The
vaccine also does not have viral RNA contaminants that cause occasional severe
reactogenecity and being in single dose vials does not contain thiomersal,” Vaxine’s
research head says.

Set up in 2002, Vaxine has started clinical trials of its other vaccines for seasonal flu,
Japanese encephalitis, Hepatitis B and bee sting allergy. Vaxine was quickly off the
block in the global race to develop a vaccine against swine flu. “Never before has a
new influenza vaccine been delivered to the clinic so far. It is extraordinary what has
been achieved in less than three months since the seed virus was first identified,” says
Dr Dimitar Sajkov, one of Vaxine’s clinical investigators. He indicated that the
success of Vaxine’s vaccine could signal the beginning of the end for old-fashioned
egg-based vaccines.
Most of the seasonal flu vaccines are grown using the chicken-egg method as the
virus is known to grow very well in this medium. Vaxine has already received many
enquiries for the supply of the vaccine from countries like Malaysia, South Korea,
Indonesia and Saudi Arabia. In mid-August, Vaxine was honored with the National
Innovation Award at the Telstra Business Awards in Sydney, recognizing the
company’s breakthrough efforts in the development of swine flu vaccine.
BioMD to trial Gynecel tissue replacement patch

Singapore, Aug 27, 2009: Perth, Australia-based biotech company bioMD said that it
will start a 20 patient clinical trial of its ‘Gynecel’ treated biomaterial patch in pelvic
floor reconstruction surgery. The independent phase II clinical trial at St George
Public Hospital in Sydney will start in the next few weeks.

The trial will aim to prove the safety and efficacy of bioMD’s unique biomaterial
tissue replacement patch in patients suffering vaginal prolapse, says the company.

The condition affects many women in Australia every year, with approximately
18,000 presenting for surgery annually. The global market for pelvic floor as well as
other abdominal surgical repair is projected to be in excess of $1 billion during 2010.

Chief Clinical Investigator for the trial and Chairman of the Sydney Women’s
Endosurgery Center, Dr Gregory Cario said, “We have been impressed by the
extensive preclinical studies conducted with this material and are encouraged by the
results from the recent cardiovascular study in children. We would prefer to use a
biomaterial mesh product rather than a synthetic mesh in order to reduce the widely
reported complications with those products. This new biomaterial, using an Australian
patented process, appears to have long-term appeal.”

bioMD’s Managing Director, Mr Michael Bennett, said the study was a significant
milestone in the company’s plans to commercialize its ADAPT treated biomaterials
used in cardiovascular and soft tissue repair procedures.

“The results of this study will support our plan to develop a range of products for
gynaecological surgeons worldwide. These products could bring a new level of
comfort and improved patient outcomes to pelvic floor reconstruction procedures for
both the surgeon and the patient,” added Mr Bennett.
Dainippon readies NDA after successful schizophrenia trial

Singapore, Aug 27, 2009: Japan-based Dainippon Sumitomo Pharma has announced
positive results from PEARL 2 - a phase III clinical trial of lurasidone for the
treatment of patients with schizophrenia. In this trial, both lurasidone 40 and 120
mg/day were said to be significantly more effective than placebo for the treatment of
schizophrenia. Lurasidone was well-tolerated with an overall discontinuation rate that
was similar to placebo.

"We are pleased with the results of this study as these data reinforce our belief that
lurasidone will be an important treatment option for patients with schizophrenia," said
Mr Masayo Tada, CEO, Dainippon Sumitomo Pharma. "We plan to submit our NDA
filing package for lurasidone to the FDA in early 2010."

PEARL 2 (Program to Evaluate the Antipsychotic Response to Lurasidone) is part of

a worldwide phase 3 clinical development program, involving more than 2,000
patients, intended to evaluate the safety and efficacy of lurasidone for the treatment of
schizophrenia. The PEARL 2 study was a double-blind, fixed-dose, placebo-
controlled clinical trial involving 478 inpatients with acute schizophrenia that were
randomized to receive either lurasidone 40 or 120 mg/day, olanzapine 15 mg/day or
placebo for six weeks. The active comparator, olanzapine, was used for purposes of
establishing assay sensitivity.

Both the dosages of Lurasidone, taken once-daily, demonstrated significantly greater

improvement versus placebo on the primary efficacy measure, the Positive and
Negative Syndrome Scale (PANSS) total score, at study endpoint. PANSS score
changes from baseline for lurasidone 40 and 120 mg/day versus placebo were -25.7
and -23.6 vs. -16.0, respectively, at study endpoint. A total of 53% of patients on
lurasidone 40 mg/day and 47% of patients on lurasidone 120 mg/day demonstrated a
30% or more improvement on the PANSS total score from baseline versus 38% on
placebo.

In addition, according to the company, both lurasidone dose groups were significantly
more effective than placebo on the Clinical Global Impressions Severity scale (CGI-
S), the key secondary efficacy endpoint. The CGI-S score changes from baseline for
lurasidone 40 and 120 mg/day versus placebo were -1.5 and -1.4 vs. -1.1,
respectively, at study endpoint.

"Patients with schizophrenia and their health care providers are in need of new
treatment options that provide consistent efficacy with a lower impact on weight,
lipids, and movement disorders," said Dr Herbert Meltzer, a study investigator and
professor of psychiatry and pharmacology at the Vanderbilt University School of
Medicine. "Lurasidone appears to be a potentially significant new treatment option for
schizophrenia."
Crucell gets positive results from rabies MAb study in Philippines

Singapore, Jun 26, 2009: Dutch biopharmaceutical company Crucell has reported the
results of a second phase II clinical study of its investigational rabies monoclonal
antibody (MAb) combination, which started in May 2008 in the Philippines.

Crucell has a collaboration and commercialization agreement with Sanofi-Pasteur, the

vaccines division of Sanofi-Aventis Group, for Crucell's rabies MAbs to be used in
association with a rabies vaccine for post-exposure prophylaxis against the fatal
disease of rabies.

This phase II trial was set up as a randomized, single-blind, controlled study in 48

healthy children and adolescents in a high endemic area of Metro Manila, Philippines.
The trial was set up to test the safety and tolerability of the antibody product in
association with Sanofi-Pasteur's Verorab rabies vaccine in a direct comparison with
the marketed human rabies immune globulin (HRIG) product. It was performed at the
Research Institute for Tropical Medicine under the leadership of Dr Beatriz P
Quiambao.

The antibody product in association with the rabies vaccine was administered to 16
adolescents as well as 16 children. Its safety and neutralizing activity was compared
to HRIG associated with the same rabies vaccine in eight adolescents and eight
children. The results of the Philippines study showed Crucell's rabies MAb
combination was safe and well tolerated. Neutralizing activity levels were similar in
the subjects administered with the antibody product or with HRIG and all study
participants reached adequate immunity levels.

This study in children further broadens the population in which Crucell's rabies MAb
combination could potentially be used. Earlier trials in adult populations have already
shown safety and neutralizing activity. Detailed results of this study will be presented
at the XX Rabies in the Americas RITA conference in Quebec, Canada on October
18-23, 2009.

"Our children are at high risk of getting rabies. The results of this study bring closer
the moment that all-in-need get an adequate treatment against rabies." said Dr Beatriz
P Quiambao, Chief Clinical Research Division and Head, Rabies Research Group,
Research Institute for Tropical Medicine, Muntiinlupa, Philippines.

On February 12, 2008 Crucell announced that its rabies MAb combination was
granted Fast Track status by the US FDA.
Bioneer releases H1N1 virus diagnostic kit

Singapore, Aug 26, 2009: Korean company, Bioneer is setting up Real Time
Diagnostic system in 30 major university hospitals and four out of five major National
Clinical Diagnostics Service Center in Korea. Bioneer is already said to have set up
over 20 different locations of Health Centers more than 17 different locations of
Health Centers and Environment Research Centers in South Korea.

AccuPower New Influenza A (H1N1) Real Time RT-PCR diagnostics kits is

developed based on the patented Premix technology to maximize reproducibility and
stability. The kit is ready-to-use lyophilized mixture that only needs to add extracted
sample RNA into the tube. Within 90 minutes, the test result will confirm negative or
positive. The kit was developed by using comprehensive alignment analysis of
Influenza virus. According to the company, the system is composed of Exicycler 96,
ExiPrep 16 and Exispin.

Bioneer is said to have released a total solution from sample prep to detection. It is
designed to detect H1N1 virus accurately by selecting the variation which were
classified between New Influenza A (H1N1) and the existing seasonal Influenza type
A. The kit is validated and being supplied to major clinical service lab and hospital in
South Korea.

The sample prep process of New Influenza A (H1N1) is said to be a very cautious
step. Especially any possibility of aerosol generation or contact should be removed
during the process. Bioneer’s ExiPrep 16 Automatic DNA/RNA Extractor can
eliminate any possibilities of aerosol generation during the prep process.

AccuPower New Influenza A (H1N1) Real-Time RT-PCR kit is developed to run in

Exicycler 96 Real-Time PCR which is CE-IVD and NEP Certified. Exicycler 96
Real-Time PCR has been awarded as superior technological system that has high
sensitivity. Bioneer is now rapidly expanding total solution for Real-Time Diagnostic
system not just in Korea, but also throughout Asia and Middle East.
 REFERENCES

http://en.wikipedia.org/wiki/Timeline_of_biotechnology

http://www.biospectrumasia.com/content/260809AUS10439.asp

http://www.biospectrumasia.com/content/270809AUS10441.asp

http://www.biospectrumasia.com/Japan_Home.asp

http://www.biospectrumasia.com/Philippines_Home.asp

http://www.biospectrumasia.com/content/260809KOR10423.asp