2015 Pak Sanofi

DEVELOPMENT &
COMMERCIALIZATION OF
BIOTECHNOLOGY
PRODUCTS IN PAKISTAN
Consultants Report
National Commission on Biotechnology
June 2009
Development and Commercialization of Biotechnology Products in Pakistan
INDEX
Page No
1. EXECUTIVE SUMMARY ................................................................ 6
2. PAKISTAN'S .................................................................................. 9
a. Development Progress
b. Development Challenges
c. Population Size, Implications for Health & Development
3. BIOTECHNOLOGY......................................................................... 11
a. Introduction
b. History
c. Recombinant DNA Technology
d. The Power of Biotechnology
4. BIOTECHNOLOGY APPLICATIONS .............................................. 15
a. Health
i. Medicine
ii. Vaccines
iii. Protein Engineering
iv. Diagnostics
b. Agriculture
c. Industrial
d. Other
i. Environmental / Bioremediation and Biodegradation
ii. Nano-biotechnology
5. USING NEW KNOWLEDGE TO DEVELOP PRODUCTS ............... 26
a. Product Discovery
b. Product Development
c. Follow on Biologicals
d. Introduction to Bioprocess
6. INTELECTUAL PROPERTY RIGHTS ............................................. 35
a. Types of Patents
b. Patentable Inventions
c. Biotechnology Patents
7. ETHICAL ISSUES .......................................................................... 38
a. Global Health
NCB Consultant Report Page 2

b. Gene Therapy
c. Germ-Line Gene Therapy Moratorium
d. Stem Cells
e. Cloning
f. Use of Animals in Research
8. BIOTECHNOLOGY INDUSTRY FACTS ......................................... 41
9. BIOTECHNOLOGY COMMERCIALIZATION IN DEVELOPING COUNTRIES 43
a. Development of Biocon India
b. The development of Heber Biotech, Cuba
c. Scope of trade
d. Market structure
e. Potential market gains
f. Potential market losses
g. Life Science Parks of Asia
10. BIOTECHNOLOGY IN PAKISTAN.................................................. 51
a. Research Institutions
b. International projects
c. Biosafety framework
11. POTENTIAL PROJECTS FOR PAKISTAN ..................................... 58
a. Industrial Enzymes
i. Xylinase
ii. Citric Acid
iii. Cellulase
b. Bio-fertilizer
c. Human Healthcare
i. Human Vaccines
ii. Therapeutic Proteins - Interferon
d. Animal Healthcare Vaccine development
i. Veterinary Vaccines
ii. Vaccine development for Foot & Mouth Disease (FMD)
iii. Vaccine development for Egg drop syndrome (Poultry Vaccine)
12. PRODUCTS AVAILABLE FOR COMMERCIAL PRODUCTIONS ... 74
13. RECOMMENDATIONS OF THE CONSULTANT ............................ 77
14. POSSIBLE DEVELOPMENT MODELS .......................................... 87

15. ANNEXURES ................................................................................. 90

a. List of Research Institutions
b. Industries That Benefit
c. Consumer Goods Made With Industrial Biotech
d. Examples of Industrial Enzymes
e. Agricultural biotech Products already in the Market
f. Time Line in Biotechnology
g. Glossary
h. References
i. Pakistan Bio-safety Rules

Biotechnology being one of the six priority areas of science & technology is included
in the MTDF 2005-10 of Planning Commission. Development and
Commercialization of Biotechnology Products is one of the goals.
In order to achieve this objective, National Commission on Biotechnology hired this

consultant under the revised PC1 to prepare a proposal / report
To evaluate and identify potential biotech products from the research institutes of
Pakistan for commercialization.
To identify linkages between industry and academia.
Formulate / recommend strategy to commercialize biotech products nationally
and internationally.
Acknowledgements
The project consultant wishes to thank the staff of National Commission on

Biotechnology for their cooperation and guidance, Dr. Zafar M. Khalid, Dr. Abid
Azhar, Dr. Yusuf Zafar, Prof Khushi Muhammad, Prof. Waheed Akhtar and many
others who provided input for this report. The major research institute contacts like
CEMB, NIBGE, KIBGE, PCSIR, NIGAB etc. provided information and answered
questions. Without their cooperation, this effort would not have succeeded.

EXECUTIVE SUMMARY
The biosciences play a key role in the economic advancement of a country. They
have immense potential in bringing together basic research innovations with new
market opportunities. Biotechnology is the application of technologies based on
living systems to develop commercial processes and products. It now includes the
techniques of recombinant DNA, gene transfer, embryo manipulation and transfer,
plant regeneration, cell culture, monoclonal antibodies, and bioprocess engineering.
Abstract ideas and concepts are being translated into practical applications through
the use of these modern bioscience techniques. For instance, in order to enhance
the resistance of some crops to certain herbicides, scientists have acquired the skill
of genetically altering these crops. Biotechnology has been particularly useful in
developing safer vaccines against viral and bacterial diseases such as foot-and-
mouth disease in animals and Measles, Hepatitis, Tetanus, Polio etc in humans.
Despite all these advances, we have barely scratched the surface Bio technology
is such a vast field that many of the potential benefits of its tools are yet to be
discovered and put to productive use.
Biotechnology has a vast capacity for enhancing crop production, animal
agriculture, and bio-processing. It can enable scientists to develop higher yielding
and more nutritious crop varieties, augment resistance to disease and adverse
conditions, or curtail the need for fertilizers and other costly agricultural chemicals.
As regards animal agriculture, its greatest use lies in therapeutics and vaccines for
disease control. Bio-processing, which utilizes living systems or their components to
create useful products, makes it possible to manufacture new products and foods,
treat and use waste materials, and utilize renewable resources for fuel.
Biotechnology also has the potential to improve forestry and its products, fiber
crops, and chemical feed stocks.
The corporate sector has expanded as a result of advancements made in human,
plant, and animal biosciences. In recent years, a steady mushrooming of companies
has been seen which are dealing with diverse areas of Bio-science, from drug
development to molecular diagnostics to biomaterials and biocomposites, biofuels,
and other bio-related products. Biotechnology has successfully developed more
than 200 new therapies including vaccines. Moreover, around 400 bio-tech drug
products are currently undergoing clinical tests to examine their effectiveness in
targeting more than 200 diseases. In fact, Biotechnology has contributed to the
creation of hundreds of medical diagnostic tests that guard the blood supply against
HIV and help in the early detection of harmful conditions to enable their successful
treatment.
During the current decade, the Biotechnology industry has been witnessing a rapid
double digit growth. This highly concentrated industry is controlled by two major

markets North America and Europe. These two comprise 97 percent of the total
revenue generated by the industry. Asian and Asia Pacific countries principally
Australia, India and China are the key emerging countries of these dominant
markets.
Crucial to biotech success has been the corporate alliances. By the close of 2006,
biotechnology companies had grown to 1,452 in the U.S. alone. The Bioscience
industry has employed around 1.2 million people and continues to create
innumerable additional related jobs globally. Bio technology, according to BioWorld,
has drawn more than $24.8 billion worth in investments in 2007 and successfully
raised more than $100 billion in the five-year span of 20032007.
At a global level, industry clusters result in the evolution of a number of new
industries. Similarly, the cluster model has been effective in driving growth and
innovation in the emerging life science industry, with start-ups and MNCs setting up
base in these geographical clusters. Almost all governments across the Asia Pacific
region have allocated resources and framed policies to propel and accelerate this
growth.
Singapores Biopolis is a centre of great research and the country has boosted its
economy by investing in its biomedical industry. India has about 25 such parks and
has established the highest number of FDA approved plants. China too is rapidly
scaling up its infrastructure and has constructed world class facilities. Developed
markets such as Australia and Korea are also depending heavily on the life
sciences industry and are building this infrastructure spread across various clusters
in the country.
Biotechnology in Pakistan stands at the crossroads. Pakistan has vast reserves
of natural resources but is faced with a number of political, social and economic
problems. Being a developing country, Pakistan suffers from a lack of political will in
implementing policies pertaining to the advancement of science and technology.
More immediate development concerns take precedence while issues related to
science and technologies are placed on a backburner.
To date, the Government of Pakistan has invested approximately Rs. 1 billion in the
field of Biotechnology and has initiated various constructive programs in natural
sciences, health, education and economic development. Yet, the prospect of
accelerated growth has continued to be impeded by limited financial resources and
ineffective and highly cumbersome administrative structures and procedures. Even
the allocated financial resources and foreign aid are distributed unequally amongst
different scientific institutions.
Despite a number of setbacks and hindrances, Pakistan has managed to achieve
some eminence in agricultural, health, industrial and environmental biotechnology. It

is therefore essential that it should dedicatedly encourage and support research

efforts in biotechnology and commercialization of the developed products.
To ensure greater economic progress, it is not a reliable strategy to focus solely on
the low-tech industrial set-up because the existing set-up is unable to sustain in a
highly competitive global market system. More profitable and sound potential
resources such as agriculture need to be explored. Biotechnology in this regard is a
revolutionary and accessible concept which has the capacity to boost the
agricultural yield and accelerate the economic rate of the country.
The National Commission on Biotechnology (NCB) has played a significant role in
developing biotech policy and framing bio-safety rules and guidelines. More
importantly, it has created awareness about biotechnology by organizing a series of
conventions between scientists and entrepreneurs with an aim to facilitate the
marketing of biotechnology products developed by the research institutes in
Pakistan. In spite of these milestones, vital issues such as Intellectual Proprietary
Rights, developing Biotech Parks and effective commercialization of biotechnology
products still need to be addressed. Talent, technology and capital are key
ingredients required to advance these issues and develop a bioscience-driven
economy.
Strong partnerships and close cooperation between the Ministries of Science &
Technology, Environment, Agriculture and Health on a long term basis are
imperative for facilitating the formulation of policies and implementation on these
issues. The establishment of a department of Bio Technology under the Ministry of
Science & Technology would help to strengthen coordination between the above
mentioned ministries. Finally, the NCB must play a permanent role as a focal
organization to promote fast paced growth in the field of Bio Technology.

PAKISTAN'S DEVELOPMENT PROGRESS

In its 62 years of independence, as measured by some key social indicators
Pakistan has made significant development progress. Health and education
services have expanded and improved, and life expectancy has increased from 59
years in 1990 to 64 in 2008. Infant and maternal mortality rates have dropped, as
have illiteracy rates. By the late-1990s Pakistan was in a position of extreme
vulnerability on the economic front, after a decade of inward-looking policies, the
country embarked on a significant economic reform program in November 1999 and
has since achieved considerable improvements.
Due to the adverse internal and external developments of an extraordinary nature,
Pakistans economy has shown great resilience against shocks of very high
intensity. Domestic factors like heightened political tensions, an unstable law and
order situation, supply shocks, coupled with external factors like worsening of
international financial crisis, and an unprecedented rise in global food and energy
prices tested the strength of economic fundamentals but Pakistans economy has
grown at an average rate of 6.6 percent per annum for the last six years but with
lowest growth rate this year.
However, despite these favorable developments, Pakistan still lags behind countries
with comparable per capita income in most social indicators. Only 40 percent of
Pakistan's population is literate, compared to an average of 64 percent of the
population in countries with similar income per capita. The reform measures
introduced by the government of Pakistan have renewed hope that these
development challenges can be tackled seriously. But this will not be achieved
without fully developing human capital, improving the investment climate, and
increasing productivity growth to bring the economy to the 5 or 6 percent annual
growth rate needed to significantly reduce poverty. In addition, a greater challenge
faces Pakistan: that of its fundamental transformation politically, economically,
socially, and with respect to gender to a modern state.
DEVELOPMENT CHALLENGES
One of the most serious concerns in Pakistan is poverty. Pakistan has an increase
in per capita gross national income (GNI) of US$1085, but it has not made any
significant impact on the poverty rates. An important observation is the difference in
income per capita across regions, which has persisted or widened. Poverty varies
drastically among rural to urban areas and from province to province, from a low of
16 percent in the northeastern areas to 44 percent in the North West Frontier
Province.

There are also significant gender gaps in both literacy and health status in Pakistan.
Gender disparities in education remain significant. While the male population
completes an average of five years of schooling, the female population in Pakistan
completes only two and a half years. The enrollment rate for boys is 77 percent as
opposed to 60 percent for girls. Maternal mortality remains high at 350 per 100,000
live births. (Target for 2015: 140/100,000)
In spite of the current economic improvements, Pakistan's external and public debts
are both quite large, and there are concerns over the vulnerability of the country's
external position and future growth prospects. The global slowdown, combined with
perceptions about security risks, due to the conflict in Afghanistan and tensions with
India, have worsened prospects for growth, exports, and Foreign Direct Investments
(FDI) in Pakistan.
Attaining the dream envisioned in the Millennium Development Goals by 2015 will
require renewed efforts in Pakistan.
Magnitude of Population and its implications for health and

development
At the time of independence the population of Pakistan was estimated to be 32.50
million which has reached to over 162 million (approx.) as of 2008. The population
in the areas now constituting Pakistan has shown a ten-fold increase since 1901;
half added during the post independence period. In fixed numbers, almost 128
million persons have been furthered to the population during the last 58 years. The
existing annual growth rate of population is anticipated at around 1.8%, which is still
one of the highest growth rates among the nine most populous countries of the
world. At this growth rate, the present population will double in year 2045. Pakistan
will have a population of about 300 million in the next 50 years even if it assumes a
quick decline in the rate of growth,
High rate of population growth has resulted in an increasingly younger population,
which is heavily weighted towards economically unproductive younger ages. The
relative size of the economically productive population has reduced, which has
resulted in an increase in the overall dependency burden (95 percent) in the
country. The dependency ratio is further affected due to low participation rate of
females in the formal labour force, resulting in an aggravation of the economic
burden on the working male population.
Source: Economic Survey of Pakistan

BIOTECHNOLOGY - INTRODUCTION
Biotechnology is the technology based on biology, especially when used in

agriculture, food science, and medicine. United Nations Convention on Biological
Diversity defines biotechnology as1: Any technological application that uses
biological systems, living organisms, or derivatives thereof, to make or modify
products or processes for specific use. An appropriate modern definition of
biotechnology would be the use of cellular and biomolecular processes to solve
problems or make useful products.
Bioengineering is the science upon which all biotechnological applications are
based. Biotechnology is often used to refer to genetic engineering technology of the
21st century; however the term encompasses a wider range and history of
procedures for modifying biological organisms according to the needs of
humankind. With the development of new approaches and modern techniques,
traditional biotechnology industries are also acquiring new horizons enabling them
to improve the quality of their products and increase the productivity of their
systems.
Since the 1970s, the term biotechnology began to be used by the Western
scientific establishment to refer to laboratory-based techniques being developed in
biological research, such as recombinant DNA or tissue culture-based processes, or
horizontal gene transfer in living plants, using vectors such as the Agrobacterium
bacteria to transfer DNA into a host organism. In fact, the term should be used in a
much broader sense to describe the whole range of methods, both ancient and
modern, used to manipulate organic materials to reach the demands of food
production. So the term could be defined as, "The application of indigenous and/or
scientific knowledge to the management of (parts of) microorganisms, or of cells
and tissues of higher organisms, so that these supply goods and services of use to
the food industry and its consumers.2
Biotechnology combines disciplines like genetics, molecular biology, biochemistry,
embryology and cell biology, which are in turn linked to practical disciplines like
chemical engineering, information technology, and biorobotics. Patho-biotechnology
describes the exploitation of pathogens or pathogen derived compounds for
favorable effect.

BIOTECHNOLOGY - HISTORY
Farmers have been selecting the best suited and highest-yield crops to produce
enough food to support a growing population at different times. Although not
normally thought of as biotechnology, this type of cultivation of crops / plants fits the
broad definition of "using a biological system to make products" and may be viewed
as the earliest biotechnological enterprise. The processes and methods of
agriculture have been refined by other mechanical and biological sciences since its
inception. Other uses of biotechnology were necessary as crops and fields became
progressively more large and difficult to maintain. Specific organisms and organism
by-products were used to fertilize, restore nitrogen, and control pests. Throughout
the use of agriculture, farmers have unintentionally changed the genetics of their
crops through introducing them to new environments and breeding them with other
plants--one of the first forms of biotechnology. Cultures such as those in Egypt, and
India developed the process of brewing beer. It is still done by the same basic
method of using malted grains (containing enzymes) to change starch from grains
into sugar and then adding accurate yeasts to produce beer. In this process the
carbohydrates in the grains are broken down into alcohols such as ethanol. Later
other cultures produced the process of Lactic acid fermentation which allowed the
fermentation and preservation of other forms of food. Fermentation was also used in
this time period to produce leavened bread. Although the process of fermentation
was not fully understood until Louis Pasteurs work in 1857, it is still the first use of
biotechnology to convert a food source into another variety.
As early as 200 BC, people have been using disabled or minute amounts of
infectious agents to immunize themselves against infections. Combinations of
plants and other organisms were used as medications in many early civilizations.
Such processes have been refined in modern medicine and have led to many
developments like antibiotics, vaccines, and other methods of fighting disease.
Modern biotechnology is thought to have largely begun on June 16, 1980, when the
United States Supreme Court ruled that a genetically-modified microorganism could
be patented in the case of Diamond v. Chakrabarty.3 Indian-born Ananda
Chakrabarty, working for General Electric, had developed a bacterium (derived from
the Pseudomonas genus) capable of breaking down crude oil, which he proposed to
use in treating oil spills.
Mounting demand for biofuels is anticipated to be good news for the biotechnology
sector. By boosting farm productivity, biotechnology plays a critical role in ensuring
that biofuel production targets are met. 4
See timelines in Annexure - f

Recombinant DNA Technology

Recombinant DNA is considered to be the foundation of modern biotechnology. The
term literally means the joining or recombining of two pieces of DNA from different
sources, such as from two different organisms.
By breeding individuals with valuable genetic traits while excluding others from
reproduction, we changed the genetic makeup of the domesticated plants and
animals. This method of selected reproduction to change the genetic material of
domesticated plants and animals began thousands of years ago. Now, in addition to
using selective breeding, we recombine genes at the molecular level using the more
precise techniques of recombinant DNA technology. Making manipulations more
precise and outcomes more certain, biotechnology decreases the risk of producing
organisms with unexpected traits and avoids the time-consuming, trial-and error
approach of choosy reproduction.
Genetic modification through selective breeding and recombinant DNA techniques
resemble each other, but there are important differences:
Genetic modification using recombinant DNA techniques allows us to move single
genes whose functions we know from one organism to another.
In selective breeding, large sets of genes of unknown function are transferred
between related organisms.
In the early 1900s, Hugo DeVries, Karl Correns and Eric Tshermark rediscovered
Mendels laws of heredity. In 1953, James Watson and Francis Crick deduced
DNAs structure from experimental clues and model building. In 1972, Paul Berg
and colleagues created the first recombinant DNA molecules, using restriction
enzymes. Ten years later, the first recombinant DNA-based drug (recombinant
human insulin) was introduced to the market. Techniques for making selective
breeding more predictable and precise have been evolving over the years. By 2000
the human genome had been sequenced and today we use recombinant DNA
techniques, in conjunction with molecular cloning to:
o Produce latest medicines and safer vaccines.
o Increase biocontrol agents in agriculture.
o Boost agricultural yields and decrease production costs.
o Decrease allergy-producing characteristics of some foods.
o Perk up foods nutritional value.
o Develop biodegradable plastics and other biobased products.
o Reduce water and air pollution.
o Slow food spoilage.

THE POWER OF BIOTECHNOLOGY

The supremacy of biotechnology is no longer a flight of the imagination. The use of
technologies based on living systems to develop commercial processes and
products now includes the techniques of recombinant DNA, gene transfer, embryo
manipulation and transfer, plant regeneration, cell culture, monoclonal antibodies,
and bioprocess engineering. By using these techniques, we have begun to
transform ideas into practical applications. For instance, scientists have learned to
genetically alter certain crops to increase their tolerance to certain herbicides.
Biotechnology has also been used to develop safer vaccines against viral and
bacterial diseases such as pseudo rabies, enteric colibacillosis (scours), and foot-
and-mouth disease in animals and Measles, Hepatitis, Tetanus, Polio etc in
humans. Yet we have barely scratched the surface of the many prospective benefits
the tools of biotechnology will fetch.
Biotechnology offers huge potential for improving crop production, animal
agriculture, and bio-processing. It can provide scientists with new approaches to
develop higher yielding and more nutritious crop varieties, improve resistance to
diseases and adverse conditions, or reduce the need for fertilizers and other
expensive agricultural chemicals. In animal agriculture, its greatest immediate
potential lies in therapeutics and vaccines for disease control. Bio-processing, the
use of living systems or their components to create useful products, offers
opportunities to manufacture new products and foods, treat and use wastes, and
use renewable resources for fuel. Biotechnology could also improve forestry and its
products, fiber crops, and chemical feed stocks.
Biotechnology offers new ideas and techniques applicable to agriculture. It offers
tools to develop a better understanding of living systems, of our environment, and of
ourselves. However, continued advances will take a serious commitment of talent
and funds.

BIOTECHNOLOGY - APPLICATIONS
Applications of Biotechnology can be grouped in four broader industrial areas,
including health care (medical), crop production and agriculture, non food
(industrial) uses of crops and other products (e.g. biodegradable plastics, vegetable
oil, bio fuels), and ecological uses.
One of the commonest applications of biotechnology is the directed use of
organisms for the manufacture of organic products (examples include beer and milk
products). Another example is using naturally present bacteria by the mining
industry in bioleaching. Biotechnology is also used to recycle, treat waste, clean up
sites contaminated by industrial activities (bioremediation), and also to produce
weapons of biological warfare.
A string of derived terms have been coined to identify several branches of
biotechnology, for example:
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." 5 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 segment.
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 conditions or in the presence (or absence) of
certain agricultural chemicals. An example of this is the engineering of a
plant to express a pesticide, thereby eliminating the need for 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 significant debate. One hope is that
green biotechnology might produce more environmentally friendly solutions
than conventional industrial agriculture.
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 management.
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 conventional processes used to manufacture

industrial goods.
The investments and economic output of all of these types of applied
biotechnologies form what has been described as the bio economy.
MEDICINE
Modern biotechnology finds promising applications in such areas as
drug production;
pharmacogenomics; to be able to design and produce drugs that are adapted
to each persons genetic makeup
gene therapy; and
genetic testing;
Biopharmaceuticals are large biological molecules known as proteins and these

usually target the underlying mechanisms and pathways of a disease (but not
always, as is the case with using insulin to treat type 1 diabetes mellitus,); it is a
relatively young industry. They can deal with targets in humans that may not be
accessible with usual medicines. Small molecules are manufactured by chemistry
but larger molecules are created by living cells such as those found in the human
body: for example, bacteria cells, yeast cells, animal or plant cells.
Modern biotechnology is often associated with the use of genetically altered
microorganisms such as E. coli or yeast for the production of substances like
synthetic insulin or antibiotics. It can also refer to transgenic animals or transgenic
plants, such as Bt corn. Genetically changed mammalian cells, such as Chinese
Hamster Ovary (CHO) cells, are also used to produce certain pharmaceuticals.
Another hopeful new biotechnology application is the development of plant-made
pharmaceuticals.
Biotechnology is also commonly associated with landmark breakthroughs in new
medical therapies for the treatment of hepatitis B, hepatitis C, cancers, arthritis,
haemophilia, bone fractures, multiple sclerosis, and cardiovascular disorders. The
biotechnology industry has also been instrumental in developing molecular
diagnostic devices than can be used to classify the target patient population for a
given biopharmaceutical. For example, Herceptin, was the first drug approved for
use with a matching diagnostic test and is used to treat breast cancer in women
whose cancer cells express the protein HER2.
Existing medicines can be manufactured relatively easily and cheaply by using
modern biotechnology. Medicines designed to treat human diseases were the first
genetically engineered products. To cite one example, in 1978 Genentech
developed synthetic humanized insulin by joining its gene with a plasmid vector
inserted into the bacterium Escherichia coli. Insulin, widely used for the treatment of

diabetes, was previously extracted from the pancreas of abattoir animals (cattle
and/or pigs). The resultant genetically engineered bacterium enabled the production
of enormous quantities of synthetic human insulin at relatively low cost6,
With the evolution of Modern biotechnology it has become possible to make without
difficulty and comparatively cheaply human growth hormone, clotting factors for
hemophiliacs, fertility drugs, erythropoietin, interferons and other drugs.7 Most drugs
today are based on about 500 molecular targets. Genomic knowledge of the genes
involved in diseases, disease pathways, and drug-response sites are expected to
lead to the discovery of thousands more new targets. 7
VACCINES
Vaccines help the body recognize and fight infectious diseases. Conventional
vaccines use weakened or killed forms of a virus or bacteria which stimulate the
immune system to create the antibodies that will provide resistance to the disease.
Usually only one or a few proteins on the surface of the bacteria or virus, called
antigens, trigger the production of antibodies. Biotechnology is helping us improve
existing vaccines and create new vaccines against infectious agents, such as the
viruses that cause cervical cancer and genital herpes.
Vaccine Production using modern Biotechnology
Most of the new vaccines consist only of the antigenic part of the microbe and not
the complete microbe which can cause disease. The vaccine is made by inserting
the gene that produces the antigen into a manufacturing cell, such as yeast. During
the manufacturing process, which is similar to brewing beer, each yeast cell makes
a perfect copy of itself and the antigen gene. The antigen is later purified from the
yeast cell culture. By isolating antigens and producing them in the laboratory, it is
possible to make vaccines that cannot transmit the virus or bacterium itself. This
method can also increase the amount of vaccine that can be manufactured because
each manufacturing cell can produce many antigens for purification. By using these
techniques, scientists have developed antigen-only vaccines against life-threatening
diseases such as hepatitis B and meningitis.
The latest research has proved that injecting small pieces of DNA from microbes is
sufficient for triggering antibody production. Such DNA vaccines could provide
immunization against microbes for which we currently have no vaccines.
The concept of vaccine is going beyond protection against infectious diseases.
Many researchers are developing vaccines against non-infectious diseases such as
diabetes, chronic inflammatory disease, Alzheimers disease, cancer and
autoimmune disorders.

Vaccine Delivery Systems

Many vaccines require special handling like refrigeration during shipping and
storage, syringes and skilled professionals to administer them. The researchers are
now working to create new vaccine delivery technologies that simplify distribution
and use. Technologies under study include oral vaccines, vaccines administered via
patch, and even edible vaccines manufactured by plants and animals.
Academic researchers have obtained positive results using human volunteers who
consumed hepatitis vaccines in bananas, and E. coli and cholera vaccines in
potatoes. In addition, because these vaccines are genetically incorporated into food
plants and need no refrigeration, sterilization equipment or needles, they may prove
particularly useful in developing countries. Researchers are also developing skin
patch vaccines for tetanus, anthrax, influenza and E. coli.
PROTEIN ENGINEERING
The technology of protein engineering is used, often in conjunction with
recombinant DNA techniques, to improve existing proteins (e.g., enzymes,
antibodies and cell receptors) and create proteins not found in nature. These
proteins may be used in drug development, food processing and industrial
manufacturing.
Protein engineering has most commonly been used to alter the catalytic properties
of enzymes to develop ecologically sustainable industrial processes. Enzymes are
environmentally superior to most other catalysts used in industrial manufacturing
because, as biocatalysts, they dissolve in water and work best at neutral pH and
comparatively low temperatures. In addition, because biocatalysts are more specific
than chemical catalysts, they also produce fewer unwanted byproducts.
Manufacturers of chemicals, textiles, pharmaceuticals, pulp and paper, food and
feed, and energy are all benefiting from cleaner and energy-efficient production
made possible with biocatalysts. Scientists are circumventing the limitations of
biocatalysts by using protein engineering to increase enzyme stability under harsh
manufacturing conditions.
In addition to industrial applications, protein engineering has been used by medical
researchers to design novel proteins that can bind to and deactivate viruses and
tumor-causing genes; create especially effective vaccines; and study the membrane
receptor proteins that are so often the targets of pharmaceutical compounds. Food
scientists are using protein engineering to improve the functionality of plant storage
proteins and develop new proteins as gelling agents. Scientists are developing new
proteins to respond to chemical and biological attacks. For example, hydrolases
detoxify a variety of nerve agents as well as commonly used pesticides. Enzymes

are safe to produce, store and use, making them an effective and sustainable
approach to toxic materials decontamination.
RECOMBINANT PROTEIN Therapeutics

Some diseases are caused when defective genes dont produce enough of the
proteins the body requires. Today we are using recombinant DNA and cell culture to
produce these proteins. Replacement protein therapies include:
Factor VIIIa blood-clotting protein missing in some hemophiliacs. Marketed by
several companies under various brand names.
Insulina hormone that regulates blood glucose levels. Diabetes results when the
body can no longer make insulin (or can no longer respond to it). Marketed by
several companies under various brand names.
Human growth hormonea hormone essential to achieving normal height.
Children with growth disorders may be prescribed a recombinant version of this
protein. Marketed by several companies under various brand names.
Betaglucocerebrosidasea protein whose absence results in Gauchers disease,
a rare genetic disorder. Marketed as Cerezyme.
Some protein therapies do not treat a protein deficiency per se. Instead, they
introduce or boost levels of a protein in order to fight a symptom or disease process.
For example, patients with anemia due to cancer chemotherapy may be treated with
recombinant erythropoietin, which stimulates the formation of red blood cells. Heart
attack and some stroke patients are often given a bolus of recombinant tissue
plasminogen activator to break up blood clots. Protein drugs can be life-savers for
acute conditions, but they are also used to treat chronic diseases, such as
rheumatoid arthritis, Crohns disease and multiple sclerosis.
DIAGNOTICS
Many diseases and medical conditions can now be detected more quickly and with
greater accuracy because of biotechnology based diagnostic tools. A common
example is the new generation of home pregnancy tests that provide more accurate
results much earlier than previous tests. Tests for strep throat and many other
infectious diseases provide results in minutes, enabling treatment to begin
immediately, in contrast to the two or three day delay of previous tests. There are
more than 1,200 biotechnology based tests in clinical use, according to
genetests.org, a site sponsored by the University of Washington. Many are for
genetic diseases, while others test predisposition to disease. Emerging applications
include tests to predict response to medicines and assist with nutritional planning.

Cost of diagnostics in many cases has been reduced. A blood test developed
through biotechnology measures low-density lipoprotein (bad cholesterol) in one
test, without fasting. Biotech-based tests to diagnose certain cancers, such as
prostate and ovarian cancer, by taking a blood sample, eliminate the need for
invasive and costly surgery.
In addition to diagnostics that are cheaper, more accurate and quicker than
previous tests, biotechnology is allowing physicians to diagnose diseases earlier,
which greatly improves prognosis. Proteomics researchers are taking this progress
a step further by identifying molecular markers for incipient disease before visible
cell changes or symptoms appear.
The wealth of genomics information now available will greatly assist doctors in early
diagnosis of diseases such as type I diabetes, cystic fibrosis, early-onset
Alzheimers disease and Parkinsons disease, ailments that previously were
detectable only after clinical symptoms appeared. Genetic tests will also identify
patients with predisposition to diseases such as various cancers, osteoporosis,
emphysema, type-2 diabetes and asthma, giving patients an opportunity to prevent
the disease by avoiding triggers such as poor diet, smoking and other
environmental factors.
Some biotechnology tests even help prevent the spread of diseases. These are the
tests used to screen donated blood for the pathogens that cause AIDS, hepatitis
and other infections.
Speedy and improved healthcare provision has been made possible by several
Biotech-based tests which are portable, so physicians conduct the tests, interpret
results and decide on treatment at the point of care. In addition, because many of
these tests give results in the form of color changes (similar to a home pregnancy
test), results can be interpreted without technically trained personnel, expensive lab
equipment or costly facilities, expanding access to poorer communities and
developing countries.
AGRICULTURE
Improve yield from crops
By using the techniques of modern biotechnology, one or two genes may be
transferred to a highly developed crop variety to impart a new character that would
increase its yield.9 However, while increases in crop yield are the most obvious
applications of modern biotechnology in agriculture, it is also the most difficult one.
Current genetic engineering techniques work best for effects that are controlled by a
single gene. Many of the genetic characteristics associated with yield (e.g.,
enhanced growth) are controlled by a large number of genes, each of which has a

minimal effect on the overall yield. 10 There is, therefore, much scientific work to be
done in this area.
Reduced vulnerability of crops to environmental stresses
Biotechnologists are studying plants that can cope with extreme conditions such as
drought and excessively salty soil, in the hope of finding the genes that enable them
to withstand biotic and abiotic stresses. One of the latest developments is the
identification of a plant gene, At-DBF2, from thale cress, a tiny weed that is often
used for plant research because it is very easy to grow and its genetic code is well
mapped out. When this gene was inserted into tomato and tobacco cells, the cells
were able to withstand environmental stresses like salt, drought, cold and heat, far
more than ordinary cells. If these preliminary results prove successful in larger trials,
then At-DBF2 genes can help in engineering crops that can better withstand harsh
environments. 11 Researchers have also created transgenic rice plants that are
resistant to rice yellow mottle virus (RYMV). In Africa, this virus destroys majority of
the rice crops and makes the surviving plants more susceptible to fungal infections.
12
Increased nutritional qualities & quantity of food crops

Proteins in foods may be modified to increase their nutritional qualities. Proteins in
legumes and cereals may be transformed to provide the amino acids needed by
human beings for a balanced diet.11
Improved taste, texture or appearance of food
Modern biotechnology can be used to slow down the process of spoilage so that
fruit can ripen longer on the plant and then be transported to the consumer with a
still reasonable shelf life. This may improve the taste, texture and appearance of the
fruit. More importantly, it could expand the market for farmers in developing
countries due to the reduction in spoilage. The first genetically modified food
product was a tomato which was transformed to delay its ripening.13 Researchers in
Indonesia, Malaysia, Thailand, Philippines and Vietnam are currently working on
delayed-ripening papaya in collaboration with the University of Nottingham and
Zeneca.14
Enzymes produced by micro-organisms provide an alternative to animal rennet, a
cheese coagulant and an alternative supply for cheese makers15. Enzymes offer an
animal-friendly alternative to animal rennet. While providing comparable quality,
they are theoretically also less expensive.
About 85 million tons of wheat flour is used every year to bake bread.16 By adding
an enzyme called maltogenic amylase to the flour, bread stays fresher longer.
Assuming that 10-15% of bread is thrown away, if it could just stay fresh another 5-
7 days then 2 million tons of flour per year would be saved. That corresponds to
40% of the bread consumed in a country such as the USA. This means more bread
becomes available with no increase in input. In combination with other enzymes,
bread can also be made bigger, more appetizing and better in a range of ways.

Reduced dependence on fertilizers, pesticides and other

agrochemicals
The focus on current commercial applications of modern biotechnology in
agriculture is on reducing the dependence of farmers on agrochemicals. For
example, Bacillus thuringiensis (Bt) is a soil bacterium that produces a protein with
insecticidal qualities. Traditionally, a fermentation process has been used to
produce an insecticidal spray from these bacteria. In this form, the Bt toxin occurs
as an inactive protoxin, which requires digestion by an insect to be effective. There
are several Bt toxins and each one is specific to certain target insects. Crop plants
have now been engineered to contain and express the genes for Bt toxin, which
they produce in its active form. When a susceptible insect ingests the transgenic
crop cultivar expressing the Bt protein, it stops feeding and soon thereafter dies as
a result of the Bt toxin binding to its gut wall. Bt corn is now commercially available
in a number of countries to control corn borer (a lepidopteran insect), which is
normally controlled by insecticide spraying.
The introduction of herbicide tolerant crops has the potential of reducing the number
of herbicide active ingredients used for weed management, reducing the number of
herbicide applications made during a season, and increasing yield due to improved
weed management and less crop injury. Transgenic crops that express tolerance to
glyphosate, glufosinate and bromoxynil have been developed. These herbicides can
now be sprayed on transgenic crops without inflicting damage on the crops while
killing nearby weeds. 17
Production of novel substances in crop plants

New uses
Other than food, biotechnology is being applied for new uses. For example, oilseed
can be modified to produce fatty acids for detergents, substitute fuels and
petrochemicals. Potatoes, tomatoes, ricererere tobacco, lettuce, safflowers, and
other plants have been genetically-engineered to produce insulin and certain
vaccines. If future clinical trials prove successful, the advantages of edible vaccines
would be enormous, especially for developing countries. The transgenic plants may
be grown locally and cheaply. Homegrown vaccines would also avoid logistical and
economic problems posed by having to transport traditional preparations over long
distances and keeping them cold while in transit. And since they are edible, they will
not need syringes, which are not only an additional expense in the traditional
vaccine preparations but also a source of infections if contaminated.18 In the case of
insulin grown in transgenic plants, it is well-established that the gastrointestinal
system breaks the protein down therefore this could not currently be administered
as an edible protein. However, it might be produced at significantly lower cost than
insulin produced in costly, bioreactors.

INDUSTRIAL
The third wave of biotechnology is already successfully competing with traditional
manufacturing processes and has shown promise for achieving industrial
sustainability. To industry, sustainable development means continuous innovation,
improvement and use of clean technologies to make fundamental changes in
pollution levels and resource consumption.
Living systems manage their chemistry efficiently, and their wastes are recyclable or
biodegradable. Biocatalysts, and particularly enzyme-based processes, operate at
lower temperatures and produce less toxic waste, fewer byproducts and lower
emissions than conventional chemical processes. They may also use less purified
raw materials. Biotechnology can also reduce energy required for industrial
processes. And it is providing new methods of monitoring environmental conditions
and detecting pollutants.
Industrial biotechnology is making manufacturing processes more efficient in many

industries, including textiles, paper and pulp, and specialty chemicals. Some
observers predict biotechnology will transform the industrial manufacturing sector in
much the same way that it has changed the pharmaceutical, agricultural and food
sectors. Industrial biotechnology will be a key to achieving industrial and
environmental sustainability.
Some of the industrial applications of biotechnology are:
Biocatalysts (Industrial Enzymes)

Biofuel
Green Plastics
NANOBIOTECHNOLOGY
The word nanotechnology derives from nanometer, which is one-thousandth of a
micrometer (micron), or the approximate size of a single molecule. Nanotechnology
is the study, manipulation and manufacture of ultra-small structures and machines
made of as few as one molecule. This was made possible by the development of
microscopic tools for imaging and manipulating single molecules and measuring the
electromagnetic forces between them.
Nanobiotechnology joins the breakthroughs in nanotechnology to those in molecular
biology. Molecular biologists help nanotechnologists understand and access the
nanostructures and nanomachines designed by 4 billion years of evolutionary
engineering i.e. cell machinery and biological molecules. Exploiting the

extraordinary properties of biological molecules and cell processes,

nanotechnologists can accomplish many goals that are difficult or impossible to
achieve by other means. For example, rather than build silicon scaffolding for
nanostructures, DNAs ladder structure provides nanotechnologists with a natural
framework for assembling nanostructures. Thats because DNA is a nanostructure;
its highly specific bonding properties bring atoms together in a predictable pattern
on a nano scale.
Nanotechnologists also rely on the self-assembling properties of biological
molecules to create nanostructures, such as lipids that spontaneously form liquid
crystals. DNA has been used not only to build nanostructures but also as an
essential component of nanomachines. Most appropriately, DNA (the information
storage molecule) may serve as the basis of the next generation of computers. As
microprocessors and microcircuits shrink to nanoprocessors and nanocircuits, DNA
molecules mounted onto silicon chips may replace microchips with electron flow-
channels etched in silicon. Such biochips are DNA-based processors that use
DNAs extraordinary information storage capacity. Biochips exploit the properties of
DNA to solve computational problems; in essence, they use DNA to do math.
Scientists have shown that 1,000 DNA molecules can solve in four months
computational problems that would require a century for a computer to solve.
Other biological molecules are assisting in our continual quest to store and transmit
more information in smaller places. For example, some researchers are using light-
absorbing molecules, such as those found in our retinas, to increase the storage
capacity of CDs a thousand-fold.
Some applications of nanobiotechnology include:
Increasing the speed and power of disease diagnostics.
Creating bio-nanostructures for getting functional molecules into cells.
Improving the specificity and timing of drug delivery.
Miniaturizing biosensors by integrating the biological and electronic
components into a single, minute component.
Encouraging the development of green manufacturing practices.
BIOREMEDIATION AND BIODEGRADATION

The elimination of a wide range of pollutants and wastes from the environment is an
absolute requirement to promote a sustainable development of our society with low
environmental impact. Biological processes play a major role in the removal of
contaminants and biotechnology is taking advantage of the astonishing catabolic
versatility of microorganisms to degrade/convert such compounds. New
methodological breakthroughs in sequencing, genomics, proteomics, bioinformatics
and imaging are producing vast amounts of information. In the field of
Environmental Microbiology, genome-based global studies open a new era
providing unprecedented in silico views of metabolic and regulatory networks, as

well as clues to the evolution of degradation pathways and to the molecular

adaptation strategies to changing environmental conditions. Functional genomic
and metagenomic approaches are increasing our understanding of the relative
importance of different pathways and regulatory networks to carbon flux in particular
environments and for particular compounds and they will certainly accelerate the
development of bioremediation technologies and biotransformation processes.19
Due to oil spills of coastal regions and the open sea, marine environments are
especially vulnerable able and mitigation is difficult. In addition to pollution through
human activities, millions of tons of petroleum enter the marine environment every
year from natural seepages. Despite its toxicity, a considerable fraction of petroleum
oil entering marine systems is eliminated by the hydrocarbon-degrading activities of
microbial communities, in particular by a remarkable recently discovered group of
specialists, the so-called hydrocarbonoclastic bacteria (HCCB). 20

USING NEW KNOWLEDGE TO DEVELOP PRODUCTS

Just understanding the biological systems is not enough, especially in medicine.
Companies must turn the information gleaned from basic research, genomics and
proteomics into useful products. The tools and techniques of biotechnology are
helpful not only in product discovery but also are useful throughout the development
process.
PRODUCT DISCOVERY
To improve the rate of product discovery is a fundamental challenge for many
sectors of the biotechnology industry. Scientists believe that current technology can
vastly reduce the time it takes to discover a drug. Moreover, biotechnology is
creating the tools to pinpoint the winning compounds far earlier in the process.
Scientists had long known the amino acid sequences of insulin and growth
hormone, it was possible to commercially produce recombinant versions relatively
soon after the advent of the technology. Discovering endogenous proteins that
stimulate the immune system and red blood cell production led rapidly to their use
as therapeutics. Other basic research has led to new products such as enzymes for
food processing or industrial manufacturing and microbes with novel biochemistry
for breaking down or synthesizing molecules.
Knowing only portions of the DNA sequence of certain genes can provide useful
products, even without knowing about the genes function or the protein it encodes.
For example, new product discoveries based solely on DNA sequence data
acquired through structural genomics include:
Diagnostics for plant, animal and human diseases.
Tests to identify the presence of genetically modified food products.
Antisense molecules to block gene expression.
Tests to identify genetic susceptibilities to certain diseases.
Tests for microbial contaminants in food products or donated blood.
Tests for drug-resistant strains of HIV and other pathogens.
Gene-based therapeutics, such as DNA vaccines and gene therapies.
The information accumulating from studies of structural and functional genomics,
proteomics and basic biology bolsters new product discovery by helping us
understand the basic biology of the process we want to control or change.
Understanding the process leads to new and better products, and sometimes
provides new uses for old products. For example, understanding the molecular
bases of high blood cholesterol and diabetes, as well as the molecular mechanism
of action of statin drugs (designed to reduce cholesterol levels), leads many
researchers to believe that statins might also help people with diabetes.

The benefits of this deeper understanding to new product discovery apply to all
industrial sectors that use biotechnology: pharmaceuticals, diagnostics, agriculture,
food processing, forestry and industrial manufacturing. Medical applications of
biotechnology illustrate how understanding molecular details encourages product
discovery.
PRODUCT DEVELOPMENT
Understanding the molecular basis of a process of interest allows many products to
be tested in cells, which can save companies time and money and lead to better
products. For example, agricultural biotechnology companies developing insect
resistant plants can measure the amount of protective protein that a plant cell
produces and avoid having to raise plants to maturity. Pharmaceutical companies
can use cell-culture and microarray technology to test the safety and efficacy of
drugs and observe adverse side effects early in the drug development process.
In addition, by genetically modifying animals to produce therapeutic protein targets
or developing advanced transgenic animal models of human diseases, we can learn
more about drug candidates in vivo effects before they enter human clinical trials.
These technologies can help companies identify the best potential drug compounds
quickly.
A single technology can be used at many steps in the development process. For
example, a small piece of DNA that the research lab uses to locate a gene in the
genome of a plant pathogen may eventually become a component of a diagnostic
test for that pathogen. A monoclonal antibody developed to identify therapeutic
leads might be used to recover and purify a therapeutic compound during scale-up.
Targeted Products
The intimate knowledge of molecular biology leads to development of highly
targeted products. For example, because we now understand the cell cycle and
apoptosis, we are better able to develop products to treat diseases rooted in these
processes. All cancers stem from uncontrolled cell multiplication and autoimmune
diseases from a failure of apoptosis. Drugs for these ailments can be targeted to
any of the molecules or cell structures involved in awry cell processes. Functional
genomics has provided information on the molecular changes that occur in
precancerous cells. With this knowledge, we can develop detection tests for
molecular markers that indicate the onset of cancer before visible cell changes or
symptoms appear.
Most of the chemotherapeutic agents target proteins active during cell division.
They make no distinction between healthy cells like hair and blood that divide
frequently and cancerous cells. Companies are developing medicines that would
stop the cell cycle of healthy cells before delivering a dose of a chemotherapeutic
agent.

Follow-on Biologicals
The first generation of biopharmaceuticals manufactured using recombinant
technologies was launched in the 1980s, and patents protecting them are now
nearing expiration. As with small molecule drugs, the expiration of patents creates
an opportunity for generic biologicals to enter the market. Due to the complexity of
biological drugs, such products are usually referred to as biosimilars or follow-on
biologics, although the term biogenerics may be applied to simple peptides.
Despite delays by the US FDA, and opposition from originator companies,
biosimilars now represent one of the most rapidly evolving areas of product
development in the pharmaceutical industry. Companies active in the biosimilars
sector are currently targeting products which are now off-patent in Europe: in
particular human growth hormone (hGH), EPO and granulocyte colony stimulating
factor (G-CSF). However, there are many more potential targets for development in
areas, which have so far attracted fewer developers in the Western markets.
INTRODUCTION TO BIOPROCESSING
Biopharmaceutical products are made using micro-organisms, plants or animals.
Micro-organisms are used as microscopic factories, and large cultures are grown in
specialised equipment. The products themselves are generated either as a result of
an organisms natural metabolism or as a result of deliberate genetic changes.
Animal cell lines (e.g. Chinese hamster ovary (CHO) cells and mouse myeloma
(NS0) cells) are engineered to produce biopharmaceuticals. Both plants and
animals are also genetically modified to generate biologic products while they are
alive. The products are recovered from the culture and subject to a number of
purification steps to manufacture the final treatment. The biological basis of the
biopharmaceutical industry introduces a level of uncertainty into the manufacturing
process because biologic products tend to be complex and not easily characterised.
In addition, the variability of biopharmaceuticals is an issue. Combined with the
need to ensure the safety of any product, this gives rise to a number of special
considerations that dictate how a manufacturing facility must be built and run.
Development of new biopharmaceuticals is a long term, high-risk process spanning
almost ten years from the earliest stage of drug discovery through approval.
Additionally, the traditional markets for biopharmaceutical products have been
small, and competition within market sectors low. As a direct result, prices for the
final products have tended to be high to recoup costs. However, as markets
increase and competition emerges, the costs of developing and manufacturing have
become more important. Whereas previously the cost of manufacture had been
considered largely irrelevant, it has now become an important consideration.

Increased competition has also placed pressure on the time-to-market, generating a

demand to reduce the typical three to five years lead-time in design and build before
production can commence. Consequently, new facilities can be commissioned well
before regulatory approval, or the decision made to use third party contract
manufacturing organisations (CMOs).
Drug Discovery Process

Discovery
(2 10 years)
Preclinical Testing
(Lab & animal testing)
Phase I
(20-30 healthy volunteers used to check
for safety and dosage)
Phase II
(100-300 patient volunteers used to
check for efficacy and side effects)
Phase III
(1000-5000 patient volunteers used to
monitor
FDA Review & Approval
Post-marketing
Testing
0 2 4 6 8 10 12 14 16
The net result is considerable pressure to streamline the development and

operation of manufacturing processes. One result has been an increase in the
number of facilities that produce more than one product. At the same time, new
applications have given rise to ever more complex products increasing the risks of
manufacturing failures. Computer simulation offers a method for optimizing existing
processes and gaining an insight into the potential design flaws of a novel
production line.
Validation
A new product can only be approved for commercial manufacture once it has
successfully completed clinical trials and product approval has been received from
the relevant regulatory body. These trials assess the safety, efficacy, and impact of
the product on patients. They are designed to establish the correct dosage and the
methods available to minimize undesirable side effects. Before the product can be

manufactured for commercial sale, it needs to satisfy both the clinical criteria and
the product validation criteria.
The biopharmaceutical development process

Hollywood is the only industry that compares to pharmaceutical manufacturing with
regards to cost and time in developing a product. A blockbuster movie costs up to
US$300M to produce and takes up to five years from the scriptwriters first
conception through to the premier in Leicester Square. Once released, success is
based on the critics reviews and the marketing strategy, which determine a films
popularity with the public.
A blockbuster biopharmaceutical costs up to US$800M6 to produce and takes 10
15 years from discovery through approval for commercialization from the regulatory
authorities. During this time, the product will have to prove itself safe and efficacious
in the treatment of disease, and the production process will need to be fully
validated to ensure reproducibility. Once released, national health services and
insurance company review panels (critics) decide whether to approve the purchase
of the product; therefore the company needs an effective marketing strategy to
illustrate the benefits of its drug. This section highlights the key stages that have to
be met along the way to commercializing a successful product.
Drug discovery
Phase III
Phase II
Phase I
Lab & Animal Testing

Drug discovery commences with the identification of a disease and the

establishment of a basic understanding of the associated pathogenic mechanisms.
There are three main stages for development:
Basic research This is carried out by government research agencies,
universities, and research companies. It reveals the disease mechanisms and
processes that may become a target for pharmaceutical intervention. Bioinformatics
plays a very large part in relaying research information among all of the interested
parties and new developments in technology for databases and communications
are making collaboration among different research groups very effective.
Translational research This is carried out by research and mainstream
pharmaceutical companies, and in some cases academia and government agencies
may be involved. This stage connects basic research to applied research and is the
first stage of drug development. The main objective is to link pharmaceutical
technologies and clinical practices to the identified target mechanisms. Once a
preliminary drug has been developed, it is tested on animals and then humans to
increase knowledge and understanding of its safety, efficacy, and possible side
effects.
Applied research This is the development and testing of medicines and is
conducted primarily by pharmaceutical companies. This process involves large
scale clinical trials that establish dosage, safety, and efficacy. Throughout this
stage, research is carried out to identify important information that should be
included on the product label. This research may be carried out by the
pharmaceutical companys research department; however it is often contracted out
to smaller research organizations and academia.
During recent years, there have been many developments in drug discovery
techniques. The original methodology was trial and error, with the very first
remedies originating in Egyptian and Roman civilizations. Techniques did not
change until the beginning of the 20th century when molecular chemistry started to
play a role in defining chemical actions. Replacing chemical techniques are those
related to molecular genetics, with an understanding of micro-organism biology and
animal immune systems. Most recent are the technologies developed since the
completion of the Human Genome Project, such as genomics and proteomics.
These platforms enable rapid expression of genetic products and the subsequent
identification of defective genes.
Process development
Once a drug has been discovered, the development of process technology bridges
the gap between the laboratory and commercialization. This stage is typically

handled by a tech transfer team, that manages the transfer of the manufacturing
technology from the research and development department to the manufacturing
facilities. There are three key stages to the development of a full-scale process:
Definition of laboratory practice The final laboratory process will have been
through many development cycles in order to successfully reproduce consistent
results. All of the logs are studied and summarized for potential processing issues
that have arisen during research.
Scale-up to pilot scale studies The movement from laboratory equipment to
process unit operations requires more than geometric scale-up. Many procedures
that are possible in the laboratory will not be suitable for large-scale operation for
example the use of shake flasks, vial centrifuges (that can achieve over 1,000,000 x
g). A particular complication arises when handling the refolding and naturation of
proteins. It is at this stage in process development that a manufacturing process is
outlined and viability studies are performed. These would typically include the
investigation of cell culture, the application of particular concentration and
purification techniques and the limiting factors associated with large
chromatography columns (for the most part, cost!).
Scale-up to production The purpose of the pilot studies is to ensure that large
amounts of capital are not wasted on process equipment that will be unsuitable to
manufacture the product. Following a successful pilot campaign, it is again the job
of the tech transfer team to design the main process. Although this instance of
scale-up is considerably simpler than the transfer from the laboratory, it has to
include all of the plant utility and layout constraints that would not have been as
detailed in the previous studies.
In addition to these three stages of development, two new methods are providing
excellent results for the industry:
Ultra Scale Down A new technique in development that allows a process to be
run at a very small scale with the same process conditions and characteristics seen
at full scale. This method helps in the early development and optimization of
production lines
Computer Simulation The objectives of computer simulation are to identify
potential bottlenecks and to detail the impact of operational changes on all stages of
bioprocessing, including utility systems and staffing shifts
Scale-up of biopharmaceutical production process to generate product for

initial R&D, clinical trials and commercialization

Lab scale production Pilot scale production Process scale production

(mg scale) (g scale) (100g - kg scale)
R&D Pre-clinical/ Commercial

clinical trials product
Source: Andrew Sinclair
Clinical Trials
A clinical trial is a scientific experiment that provides information about the
effectiveness of a drug its efficacy. They are a crucial part of drug development
offering a structured and highly regulated framework for the testing of
pharmaceuticals within animals and humans. The estimated time for a new
pharmaceutical is 10 years, and only one out of ten drugs that enter clinical
investigation will be released as products. The drug development process is
lengthy, complex and highly risky. It involves drug discovery, laboratory testing,
animal studies, clinical trials, and regulatory reviews. The biopharmaceutical
companies take extraordinary measures to ensure that a potential drug is safe and
effective by subjecting it to a series of tests. There are several different stages to
clinical development.
Pre-clinical carried out in animals
Phase I small population of healthy volunteers, assesses safety and tolerability;
70% of products will continue to Phase II
Phase II initial testing in patients, the focus is on efficacy, safety, and dose
range. This is sometimes split into two stages. The initial stage is a pilot study to
check theory, and the second stage checks that it works; 45% of products will
continue to Phase III
Phase III testing in wider range of patients, proves further efficacy and safety.
This is also often split into two stages, in which the second stage tests the new drug
against competitors; 70% of products make it through to market authorisation
Phase IV post-marketing studies, very wide ranging, further evaluation of safety
The methods for comparing drugs are obviously dependent on the ability to
substitute one for another, like for like. The following methods of structuring the
trials offer investigators flexibility to find out specific information about a
pharmaceutical:

Time-to-market
Confronted with competitive pressures of limited finances and tight timelines,

biotech companies worldwide are racing to bring new biological products to market.
Once the recombinant DNA expression system for a new drug is defined and a
patent application submitted, it is essential to complete process development and
obtain regulatory approval as rapidly as possible. Such timely approval and
marketing of drugs is crucial to gain substantial market share and secure a good
profit margin. If the product is not delivered on time to the market, the company may
lose share to competitive products, which can result in a considerable loss of sales
revenue. A days delay in gaining regulatory approval and product availability could
be worth $1 million in lost sales. In addition, the product lifetimes of
biopharmaceuticals are shrinking due to intense competition, which leads to
reduced earnings in an era with increased product testing, licensing, and operating
costs. It is imperative therefore that the biopharmaceutical companies accelerate
the time-to-market while reducing the costs of development in order to maintain
attractive economic returns.
Current estimates for the time-to-market of a biopharmaceutical drug fall in the
range of five to 12 years, with an average of seven to eight years. Most of this time
is spent in the clinical phases. The license application review period has shortened
over the years, but longer clinical phases due to the need for complex and
sophisticated technologies used to characterise and manufacture biopharmaceutical
products are now extending development times. The growing complexity and length
of the clinical trials has resulted in increased development costs. The
biopharmaceutical industry is working together with the regulatory authority to
shorten time for clinical trials so as to speed up public access to effective
biopharmaceutical medicines.

INTELLECTUAL PROPERTY
Biotechnology is an industry of ideas and invention. One of the important asset a
biotech company has is in the form of patents. These are often small companies
with 50 or less employees who are developing products that can take upto15 years
and hundreds of millions of dollars in investment to bring to the marketplace.
Intellectual property protection is so critical that a 1980 case is credited with helping
launch the biotech industry. In Diamond v. Chakrabarty, the court held that
anything under the sun that is made by the hand of man (including modified cells
and other biological materials) may be patented.
Patent
An agreement between the government and an inventor whereby, in exchange for
the inventors complete disclosure of the invention, the government gives the
inventor the right to exclude others from making, using, selling or importing the
invention for a limited time is called a patent. The property right provided in a patent
is quite different from what is commonly thought of. The granted right is to stop
others from making, using, offering for sale, selling or importing the invention.
The United States Patent & Trademark Office (PTO) evaluates patent applications
and issues patents which usually last 20 years from the date on which the patent
application is filed. Thus, the enforceable term of a patent is between 17 and 20
years and PTO provides a three-year period for the agency to issue a patent.
Biotechnology, which is highly regulated industry, the effective period of patent
protection, may be much less than 17 - 20 years. For example, consider a drug
whose patent is issued during Phase I trials. Before it can enter the market, the drug
still has to undergo at least two more rounds of clinical testing and an evaluation
period at the FDA, all of which may take five to 10 years. Its patent may be granted
years before FDA approval, thus starting the clock before the product can be sold.
By the time the drug reaches patients, it may have less than 10 years of patent
protection left.
Once a patent is expired, anyone can make, use, offer for sale, sell or import the
invention without permission of the patentee.
Types of Patents
Patents fall into three categories: utility, design and plant patents:

Utility patents are granted to those who invent or discover new and useful
machines or processes.
Design patents are issued to inventors of new, original and ornamental design for
an article of manufacture.
Plant patents are given to those who invent or discover and then asexually
reproduce a new plant type.
The Purpose of a Patent

The underlying principle for a patent system is to provide an advantage to society
as a whole by rewarding the development of new inventions. Therefore, the basic
purposes of patent system, is to promote the advancement of technology and to
protect the inventor.
Patentable Inventions
Various types of invention can be patented under U.S. law:
A processfor example, a process of making a chemical by combining chemical
X with chemical Y, or a method of treating a cancer patient by administering a
specific drug.
A machinefor example, a flat-screen, high-definition television set or an X-ray
machine.
An article of manufacturefor example, a silicon computer chip or a specially
molded piece of plastic for an automobile bumper.
A composition of matterfor example, a new pharmaceutical drug or a new
plastic for use in kitchen counters.
Any new and useful improvement to an invention that falls under any of these
categories.
Naturally occurring organisms, laws of nature, natural or physical phenomena and
abstract ideas cannot be patented.
Biotechnology Patents
Biotechnology inventions generally fall into one of the following classes:
1. New compositions of matter related to:
a. Newly discovered isolated nucleic acids
b. Proteins

c. Pharmaceutical inventions based on these nucleic acids or proteins or

cell lines transformed by nucleic acids
One cannot patent a naturally occurring gene or protein as it exists in the body, but
one can patent a gene or protein that has been isolated from the body and is useful
in that form as a drug, screening assay or other application.
2. Methods of making the above products through, for example, transformation
technology or cell culture technology.
3. Methods of treating patients with a given disease through the use of a particular
gene or protein. Even if someone has a patent on a gene or protein, a second
inventor can obtain a patent on a new use of that gene or protein, if the second
inventor discovers a new use for the substance. Such methods of treatment can
also include delivery mechanisms.
4. Methods of detecting or monitoring disease states such as through detection
assays.

ETHICAL ISSUES
Some of the numerous social and ethical issues associated with biotech research,
product development and commercialization are discussed here.
GLOBAL HEALTH
Although, biotechnology has amazing potential to improve the health and well-being
of people in the developing world, but significant obstacles exist to the development
and distribution of diagnostics, therapeutics and vaccines for the infectious diseases
prevalent in developing countries. To explore the hurdles and devise mechanisms
for circumventing them, several non-profit organizations like Bill and Melinda Gates
Foundation works with companies, donors and investors to bring new vaccines,
therapies, diagnostics and delivery tools to market in developing nations.
Gene Therapy
The field of gene therapy continues to focus on patients with severe and life-
threatening diseases who usually have few treatment options or who have failed all
available therapies. Thousands of patients have now received somatic cell (non-
reproductive cell) gene therapies targeted at life-threatening genetic diseases,
cancer and AIDS.
Gene therapies continue to be in early stages of development because researchers
are methodically exploring options for routes of administration, dosing regimes,
patient populations, indications, combination therapies and novel vectors.
Gene therapy is subject to greater oversight than virtually any other therapeutic
technology. NIH guidelines require federally funded institutions and their
collaborators to submit detailed information about proposed and ongoing clinical
trials of gene therapy products and much of this information must be disclosed to
the public. The combined activities and responsibilities of the FDA, through its
statutory role as the regulator of drug development, and the NIH/Recombinant DNA
Advisory Committee (RAC), as the forum for public discussion, have served to
protect patients while ensuring that important research moves ahead.
Germ-Line Gene Therapy Moratorium

For more than a decade, the academic and industrial research communities have
observed a voluntary moratorium on human gene therapy procedures that would
affect the germ-line cells the egg and spermthat pass on genetic composition.

Stem Cells
Researchers can now separate early, undifferentiated stem cells from blastocysts
(the 5-day-old ball of cells) that eventually develops into an embryo. Such
embryonic stem cells can differentiate into any cell type found in the human body;
they also have the capacity to reproduce themselves. The ability to maintain stem
cell lines in culture and direct their development into specific cell types holds the
potential to save many lives by controlling cancer, re-establishing function in stroke
victims, curing diabetes, regenerating damaged spinal cord or brain tissue and
successfully treating many diseases associated with aging. These undifferentiated
cells lines are also powerful research tools. By studying these cells, scientists will
begin to understand the mechanisms that guide cell differentiation and de-
differentiation.
There were several major scientific breakthroughs in stem cell research during
2007-8. Researchers claimed that they had created human embryonic stem cell
lines without destroying human embryos; other researchers announced that they
had reprogrammed adult stem cells to behave like embryonic stem cells. These
discoveries are still in the early stages, and it is not yet clear whether they will yield
cell lines useful for the development of new treatments and cures.
Cloning
The process of replication of genes, cells or organisms in a laboratory, from a single
original entity is called cloning. Another type of cloning involves somatic cell nuclear
transfer to an egg, as described above. However, as the egg divides, the
undifferentiated cells are kept in culture and never implanted. A few days after cell
division begins, stem cells are separated from the rest of the cells.
The stem cells continue to divide, creating a cell line that is genetically identical to
the somatic cell from which the nucleus was removed. Undifferentiated cells that are
genetically identical to the patient have remarkable therapeutic potential. Given the
proper environments, these cells could develop into new tissues that could replace
diseased tissues and cure diseases such as diabetes, Parkinsons, Alzheimers and
various types of cancer and heart disease. This avenue of study could produce
replacement skin, cartilage and bone tissue for burn victims and nerve tissue for
those with spinal cord or brain injuries. Research also continues regarding the
environmental cues, genes and structures that direct cell differentiation into whole
organs composed of different tissue types. This application of cloning technology is
often referred to as therapeutic cloning, or somatic cell nuclear transfer (SCNT).
One reason for doing SCNT is to understand the process of reprogramminghow
the egg cell takes genetic material from a fully differentiated cell and turns it back

into an undifferentiated cell. Once that process is understood, egg cells would not
be needed and this process could be replicated in a lab.
Due to the significant potential of cellular cloning to cure diseases and restore
function of diseased tissues, in 2002 the National Academy of Sciences released a
report supporting the use of cloning for therapeutic purposes, but opposing its use
for reproductive cloning. BIO agrees with Academys conclusions and positions.
Use of Animals in Research

Research involving animals has been critical to understanding the fundamental
processes of human biology that are so integral to modern medicine. Biotech
companies have depended on this research to develop more than 200 drugs and
vaccines approved by the U.S. Food and Drug Administration, helping more than
800 million people worldwide and preventing incalculable human suffering.
In addition to human therapeutics, animal research has also been critical to the
development of biotechnology-derived veterinary biologics and vaccines approved
by the USDA to improve the health of livestock, poultry and companion animals.
Genomics, transgenics and cloning technologies provide new approaches for
advancing the quality and efficiency of meat, milk and egg productionand in
reducing the environmental impact of agriculture. These technologies are also being
used to help preserve endangered species.

INDUSTRY FACTS
The biotechnology industry emerged in the 1970s, based largely on a new
recombinant DNA technique whose details were published in 1973 by Stanley Cohen
of Stanford University and Herbert Boyer of the University of California, San Francisco.
Recombinant DNA is a method of making proteinssuch as human insulin and other
therapiesin cultured cells under controlled manufacturing conditions. Boyer went on
to co-found Genentech, which today is biotechnologys largest company by market
capitalization.
Biotechnology has created more than 200 new therapies and vaccines, including
products to treat cancer, diabetes, HIV/ AIDS and autoimmune disorders.
There are more than 400 biotech drug products and vaccines currently in clinical
trials targeting more than 200 diseases, including various cancers, Alzheimers
disease, heart disease, diabetes, multiple sclerosis, AIDS and arthritis.
Biotechnology is responsible for hundreds of medical diagnostic tests that keep the
blood supply safe from HIV and detect other conditions early enough to be successfully
treated. Home pregnancy tests are also biotechnology diagnostic products.
Agricultural biotechnology benefits farmers, consumers and the environmentby
increasing yields and farm income, decreasing pesticide applications and improving soil
and water quality, and providing healthful foods for consumers.
Environmental biotech products make it possible to clean up hazardous waste more
efficiently by harnessing pollution-eating microbes.
Industrial biotech applications have led to cleaner processes that produce less
waste and use less energy and water in such industrial sectors as chemicals, pulp and
paper, textiles, food, energy, and metals and minerals. For example, most laundry
detergents produced in the United States contain biotechnology-based enzymes.
DNA fingerprinting, a biotech process, has dramatically improved criminal
investigation and forensic medicine. It has also led to significant advances in
anthropology and wildlife management.
The biotech industry in US is regulated by the U.S. Food and Drug Administration
(FDA), the Environmental Protection Agency (EPA) and the Department of Agriculture
(USDA).
As of Dec. 31, 2006, there were 1,452 biotechnology companies in the United
States, of which 336 were publicly held.*
Market capitalization, the total value of publicly traded biotech companies (U.S.) at
market prices, was $360 billion as of late April 2008 (based on stocks tracked by
BioWorld).

The biotechnology industry has mushroomed since 1992, with U.S. health care
biotech revenues from publicly traded companies rising from $8 billion in 1992 to $58.8
billion in 2006.*
Biotechnology is one of the most research-intensive industries in the world. U.S.
publicly traded biotech companies spent $27.1 billion on research and development in
2006.*
There were 180,000 employed in U.S. biotech companies in 2006.*
The top five biotech companies invested an average of $170,000 per employee in
R&D in 2007.
In 1982, recombinant human insulin became the first biotech therapy to earn FDA
approval. The product was developed by Genentech and Eli Lilly and Co.
Corporate partnering has been critical to biotech success. According to BioWorld, in
2007 biotechnology companies struck 417 new partnerships with pharmaceutical
companies and 473 deals with fellow biotech companies. The industry also saw 126
mergers and acquisitions.
Most biotechnology companies are young companies developing their first products
and depend on investor capital for survival. According to BioWorld, biotechnology
attracted more
than $24.8 billion in financing in 2007 and raised more than $100 billion in the five-year
span of 20032007.
The biosciencesincluding all life-sciences activitiesemployed 1.2 million people
in the United States in 2004 and generated an additional 5.8 million related jobs.**
The average annual wage of U.S. bioscience workers was $65,775 in 2004, more
than $26,000 greater than the average private-sector annual wage.**
The Biotechnology Industry Organization (BIO) was founded in 1993 to represent
biotechnology companies at the local, state, federal and international levels. BIO
comprises more than 1,200 members, including biotech companies, academic centers,
state and local associations, and related enterprises.
*New data are expected in mid-2008 from Ernst & Young, which publishes an annual
global overview of the biotechnology industry.
** The data are from a BIO-sponsored Battelle Memorial Institute report, Growing the
Nations Biotech Sector: State Bioscience Initiatives 2006. A new, updated report is
expected to be released in 2008.
Source: Biotechnology Guide 2008

Biotechnology commercialization in developing

countries
The government has been running programs to commercialize biotechnology in
developing countries. However, research and development of biotechnology are
mainly under the control of private firms in Developed countries. Therefore,
alliances between private firms from the already developed countries and public or
private institutions in the developing countries will be viewed with suspicion unless
the developing countries manage to stimulate private sector participation in
biotechnology.
The number of biotechnology companies, research institutions and

industrial associations in selected regions and countries
Region/country Companies Research institutions Industrial associations
Africa 43 41 1
Argentina 50 20 1
Australia 190 35 1
Brazil 35 >35 1
Canada 361 30 10
China 20 2 1
India 500 90 1
European Union 1500 >1000 19
Japan 400 1
Mexico 90 30 1
United States of America 1457 NA 37
Source: Biotechnology Industrial Organization and Ernst and Young, 2002.
Gradually but progressively, developing countries are adopting transgenic products.

In 1996, only 3 countries grew transgenic crops which drastically increased to 8 in
2001. Likewise, a tremendous increase in the area planted with transgenic crops in
developing countries has taken place. Argentina has been successful in accounting
for about 80 per cent of the acreage in developing countries furthermore the
People's Republic of China in 2001 had confirmed threefold expansion in acreage.
Plants are at the centre stage of the current biotechnology uprising for manufacture
of pharmaceuticals, fine chemicals, industrial enzymes and other products that are
not essentially food or feed. Unfortunately, the debate over the safety of genetically
modified organisms for human health and environment has undermined the
importance of plant biotechnology as a supply of renewable fuels, degradable
plastics, rubbers, adhesives and other products derived from fossil fuels, in addition
to industrial and food products.

Even certain drugs, namely aspirin and menthol, which are presently in use, have
been taken up from plants which are then manufactured chemically to meet quality
demands and economic concerns. By either enhancing levels of the desired
ingredient(s) in the plant or improving the efficient recovery and quality of final
product, biotechnology may be able to substitute better production systems of plant
products.
There is still room for improvements in this field which is why development is still
taking place. Underprivileged countries with exceptional growing conditions for
tobacco, potatoes and corn, among others have a good opportunity to become the
future hub for biofarming centers. Countries with the facility to purify, produce and
package these products may have extra benefits. Still under development are the
national regulatory regimes and international governance policies of transgenic
crops engineered to produce drugs. To facilitate contribution and participation of
developing nations will depend upon the flexibility, responsiveness and
inclusiveness of these regulations.
Examples of biotechnology commercialization efforts in

developing countries
Development of Biocon India

The progress of Biocon India demonstrates the significance of international
alliances. The corporation was established in 1978 in Bangalore as a joint venture
involving Biocon Biochemicals of Ireland and local interests. The company started
with the manufacture of easy fermentation goods and later embarked on its own
R&D program that saw it become a key competitor in the fields of modern
biotechnology. The R&D hard work was motivated by the need to diversify the
companys product portfolio. One of the first efforts was to replace Konji which was
imported from Japan with a local carefully fermented mass of cooked soybean meal
and roasted wheat. This is a good supply of amylases and proteases, enzymes
crucial in the hydrolysis of carbohydrates and enzymes.
The original process was intricate and mainly available in Japan but after three
years, Biocon India effectively mastered the method, leading to new fermentation
stages and enzymes that matched those from Japan. Biocon Ireland was confident
about these accomplishments, which bought products from the company. Biocon
India became a vendor of latest fermentation equipment, and two manufacturing
plants were specially made to meet the demand. Subsequently, Biocon India
became a supplier of food enzymes to United States and European markets. In
addition to enzyme production, the company also invested in the development of
new production systems that had the advantages of solid state and submerged
fermentation.. After five years of endeavor, the team developed Plafractor, a solid
phase fermentation stage with computerized and programmable controls, allowing
consistency, repeatability and reproducibility. It is also a closed system that protects
the operator and the environment from any toxic agents produced during
fermentation. Further, it allows the rapid and convenient recovery of fermentation
products and conserves space and labor. The patented bioreactor won the 2001
Biotechnology Product and Process Development Award from the Indian

Department of Biotechnology in the Ministry of Science and Technology.
The success story of Biocon India is an example of the importance of international
partnerships. While Biocon India carried out innovations and production, Biocon
Ireland provided the market for its products, enabling the newly formed firm to have
a steady flow of income as well as eliminating marketing costs of products. In 1989,
Unilever acquired Biocon Ireland and its 30 per cent share in Biocon India.
Unilevers financial muscle and global standing gave Biocon new linkages and
access to funds. Biocon learned Unilevers global operations, standards and
financial methods.
With expanded operations, Biocon India has ventured into other fields such as
pharmaceutical research. It established Syngene, which in turn spun off Clinigene
International as a wholly owned subsidiary. Syngene has close collaborations with
AsraZeneca, Glaxo and BMS, which contribute to its research efforts. Clinigene
specializes in genomics and clinical studies to support the pharmaceutical section of
the Biocon Group. Biocon has thus developed rapidly through strategic partnerships
with end users of its products. Research, to a great extent, has been driven by the
demand of its customers, resulting in accumulation of proprietary technology and
development of products and processes. This flow of information between producer
and end user was an important input in R&D activities.
Biocon India went through a steep learning curve in global management, standards
and negotiations. It exploited the chances that were presented to it, through
association with global companies, to expand its markets and product range. All
these lessons helped the company to consolidate its position, identify funding
opportunities and take advantage of market availability. The creation of different
units into individual companies spurred their expansion, depth of research and
product development. The autonomy enjoyed by the different units soon led to
innovations that became the basis of new companies and new associations with
other companies outside the group. Biocon India represents one model of
biotechnology commercialization that depends largely on international partnerships
and alliances. It carries with it the attributes of inclusion that should be encouraged
in the development of industrial and environmental biotechnology.
The development of Heber Biotech, Cuba

Cuban experiences in biotechnology commercialization also demonstrate the case
of market inclusion through international coalitions. The Center for Genetic
Engineering and Biotechnology (CIGB) has about 192 laboratories in total,
equipped with the best instruments from countries such as Japan, Germany and
Sweden. These facilities produce vaccines for meningitis B and hepatitis B.
Vaccines for HIV, haemophilia and cholera are under development. In diagnostics,
CIGB has produced analytical systems capable of detecting HIV, hepatitis B, herpes
simplex, Chagas, leprosy and other diseases. It has also produced probes for plant
diseases, about 50 enzymes (some of which are produced only in Cuba), and 160
medical and pharmaceutical products.

Cuba formed a semi-private venture known as Heber Biotech and moved into the
commercialization of biotechnology products. By 1998, Heber Biotech was
recording about $290 million in sales of hepatitis B vaccines and its
pharmaceuticals in 34 countries. The company also had representatives in about 50
countries. Nationally, biotechnology was placed just behind tourism, nickel
production and tobacco in terms of export earnings. The company is extending its
partnerships with other developing countries. For example, in 2001, it established a
joint venture with Kee Pharmaceuticals of India, in Haryana. This marketing venture
is aimed at getting access to the Indian market through special pricing and
technology transfer. Some of the companys main products, such as a recombinant
of streptokinase called cardiostrep, is used for the hydrolysis of coronary clots or
prevention of heart attacks and has a potential market value of about $11 million per
year. The market value is expected to grow by 30 per cent annually. Other products
involved included interferon and human transfer factor, also owned by Heber
Biotech.
Cuba recognizes that participating in the global market involves forging alliances
with a wide range of enterprises, especially those that have extensive marketing
networks. For this reason, a US-based multinational firm, Pfizer, is marketing some
of Heber Biotech's biotechnology products, such as the meningitis B vaccine.
Cubas biotechnology industry is an example of the importance of political
leadership on technological matters, domestic funding for research activities,
creation of appropriate research institutions, and international alliances for product
commercialization. The future of the Cuban biotechnology program will depend on
the degree to which these elements are maintained, especially in the face of
worsening economic conditions that might divert allocation of resources and political
commitment to other sectors.
The existence of a critical mass of scientists in natural and applied sciences as well
as a political commitment to technological innovations is the main factor leading to
Cuban success in biotechnology. From its investments in biotechnology over the
last two decades, Cuba can earn much more benefits if the markets of United
States are opened to Cuban products and the cooperation between Cuban
scientists and their American counterparts will increase.
Scope of trade
The evolution of market opportunities for biotechnology is not easy to forecast,
partly because of the promising nature of the industry, lack of public awareness and
a need for concentrated efforts to advance the policy environment for the
dissemination of biotechnology products. A likely emerging scenario seems to be
dominated by niche markets in a wide range of sub-sectors. Furthermore, the
undefined boundaries between agriculture, health and industry, makes difficult to
predict potential areas of market expansion. Even though the life science industries
model is at present being questioned, the basic nature of the technology
recommends that companies that have a reputable lead in pharmaceutical or
agricultural biotechnology are more likely to become equally important players in
industrial biotechnology.

However, a wide range of starting points in industrial biotechnology could lead to

expansion. For example, enzymes are likely to grasp a world market value of $1.6
billion, of which North America and Europe account for 35 per cent and 31 per cent,
respectively. During the period 1992 1998, split of the enzymes market in the
textile and detergents sectors diminished, while that in animal feeds, specialty
chemicals and food applications increased at least fivefold.
Asia has the fastest growing market for feed additives, presently estimated to be
over $6 billion globally, followed by Latin America. Amino acids and vitamins
account for about $3 billion, digestive enhancers for about $1.3 billion and disease
preventing agents for $480 million. The amino acid and digestive enhancers market
is predicted to continue growing. The market for probiotics should continue to grow,
following the opening of legislation in Europe and other countries to ban the use of
antibiotics in animal feed.
However, it is also important to note that a number of the current biotechnological
products are more expensive than their traditional equivalents. Biopesticides are still
lagging behind chemical pesticides due to target specificity, instability and batch
variation. This makes the marketing and production of biopesticides difficult and
their use by farmers, households and industry unattractive. They are estimated to
be worth about $380 million (or $74 million without Bacillus thuringiensis) out of an
estimated $8 billion pesticide market.
In developed countries, bioplastics and biofuels have been more costly than
customary plastics and petroleum-derived equivalents. Even though the
environmental benefits with the use of these products are difficult to assess,
bioplastics and biofuels remain worthwhile areas for development. Bioplastics are
now frequently used in hospitals and in home products and disposable utensils.
Moreover, the costs of petroleum products are different in developing and
developed countries, which makes them attractive in the former. It is along these
lines that genetic engineering may increase the value, but reduce the cost of
production of these products.
The impact of biotechnology on industry is liable to increase in the coming years,
and it will spread from the farm to the manufacturing segment. As new materials
with enhanced properties are developed, the need for superior household, industrial
and scientific products will increase. Most of the products we touch, wear and see
are already produced, in one way or another, through the use of biotechnology
derived products. The use of modern tools like genetic engineering or recombinant
DNA technology, will transform many of these processes and products to higher
levels of efficiency not yet experienced.
Market structure
The market is presently being dominated by biotechnology powerhouses in
developed countries. The main companies dealing in chemical, oil, agricultural, food
and pharmaceuticals are also major competitors in biotechnology, which in itself is
good for technological development through increased investments. However, there
is pessimism about these firms, which have not made any efforts in transferring
technology to developing countries in the past, will modify their approach regarding

biotechnology development. United States and Europe have invested in

biotechnology infrastructure, human capital and research activities; therefore market
is heavily dominated by them. Other important players include Canada, Japan,
Australia, China, India and Cuba.
Some of the leading R&D centers, producers and exporters of biotechnology
products are in these countries. It is probable to conclude where many players are
situated by recognizing the major producers and their chief consumers, as well as
the markets that they serve. Enzymes and plastics give an indication of
biotechnology market shares. Most of the industrial enzymes are produced in
Europe and the United States, while most of the plastics are consumed in Asia,
followed by North America and Europe. Biotechnology appliance in industry is
following style akin to those observed in agricultural and pharmaceutical sectors,
where the major producers grow clarifications that are custom-made to meet the
needs of their markets. This pattern is reinforced by alliances between technology
developers and end-users.
Potential market gains

For many developing countries Biofertilizers can be an affordable industry. The use
of inorganic fertilizer in many African countries has increased soil acidity, reducing
the yield per ton of fertilizer over time. Biofertilizers are relatively cheaper to
manufacture, suitable for small-scale farmers if produced locally thereby eliminating
distribution costs, and the investment in technology is far lower than that of
inorganic fertilizers. Biofertilizers have been produced, packaged and sold
commercially in India, while in a number of African and Latin American countries,
biofertilizers have been produced at national research centers. Most importantly, the
demand for biofertilizers has outstripped production in almost all these countries. It
is estimated that about $40,000 to $50,000 is required to build a 100-150 metric ton
biofertilizer plant. Alternatively, $500,000 for 10 plants in different locations could
produce up to 1000-1500 MT to meet the demand by rural farmers. Biofertilizers
have a demand in local market and possibly internationally as well if the production
capacity is increased.
The increasing urbanization of most developing countries has caused the
emergence of health problems like dental caries, diabetes, obesity, cancers and
cardiac diseases often thought of as being Western problems with the result in
rising demand for body and health products. It is a rapidly expanding industry that
offers growing prospects for both developed and developing countries.
Nutraceuticals already have a big market in developed and developing countries.
The demand for natural remedies is likely to increase and present a market for
developing countries endowed with wide biodiversity.
The agriculture and food industry in many developing countries is still facing quality-
related problems, due to their continued use of chemical preservatives and
pesticides that many international markets are unwilling to accept. The use of
natural products to inhibit bacteria and fungal growth will improve the acceptability
of products. Further, most of the enzymes involved are now easy to prepare locally
or could be obtained in the international market at a fair price from different sources.

The products to be affected will include fruit and vegetable preparations, fish and
meat products and fresh grains (e.g. corn) exports.
Developing countries could expand their exports using biotechnology in textiles and
leather industry. Many of the recently industrialized countries in Asia have already
registered a marked increase in textile exports. Biotechnology in these areas has
been and continues to be used to increase product quality, reduce waste and save
energy. The use of biotechnology in leather and textiles industry should increase
with many of the biotechnology companies moving into developing countries
exploring new markets.
The mining sector is the mainstay of many developing countries and its contribution
to the economy is often large. The technology currently on the market has focused
on the large mining conglomerates that produce copper, gold, zinc, nickel and other
bulky metals. The semi-precious mining sector (the small mining sector, as it is
popularly called) has attracted very little attention from technology developers,
despite its importance. This sector could increase its share of earning, if appropriate
technology is developed.
Enzymes, vaccines and some drugs in future will be produced by plants and
animals and will require processing. Developing countries will need to acquire
capacity, not only to produce, but also to process products. The international market
for industrial enzymes and products is large. It presents an area of interest in which
developing countries such as India and China are already involved. For example,
the company Maps (India) has registered growth of above 150 per cent per year
and is an exporter of industrial enzymes. It should be possible for other developing
countries to develop their own industrial products that supply their home industries
and compete on the international market.
Potential market losses

The firms that invest in biotechnology early enough are the ones that are likely to
take advantage of these market opportunities and gains mentioned above as these
will not occur automatically. This may also suggest that large enterprises with an
edge in technological innovation stand the best opportunity to make inroads into the
emerging markets. But such advances, especially in a world marked by growing
industrial inequalities, could trigger market opposition and even resistance to
biotechnology. It is therefore important to understand and raise awareness about
the market risks posed by the new technologies, in order to appreciate their
potential for wider commercialization of biotechnology products.
When biotechnology products replace conventional sources of raw materials or
where chemical processes are replaced by bioprocesses, market losses are likely to
take place in these areas. The fact is that product substitution is likely to occur.
Indeed, the new innovations are expected to have an impact on the composition of
products and processes. Equally critical is the design of mechanisms that allow for
the wider distribution of benefits and risks. The participation of petro-chemical
enterprises in the new technology is essential for the wider diffusion of
biotechnology, mainly because perceptions of potential market losses are likely to
be high in these sectors.

Life Science Parks of Asia

Industry clusters have long led the development of various industries, globally. In
the emerging life science industry as well, the cluster model has been effectively
driving growth and innovation in the life science industry, with start-ups and MNCs
setting up base in these geographical clusters. Almost all governments across Asia
Pacific region have allocated resources and framed policies to drive this growth.
Today, Singapores Biopolis is where some of the great research work is on and the
country has given a leg up to its economy with this thrust to biomedical industry.
India has about 25 such parks and already boasts of the highest number of FDA-
approved plants. China is rapidly scaling up infrastructure and has build world class
facilities. Mature markets like Australia and Korea also are banking heavily on life
in the country.
The specialized infrastructure is certainly doing much good to the industry.
According to a recently released report on bioclusters, seven of the top 10 big
pharma and more than 110 indigenous Chinese CRO are operating out of the
Zhangjiang Drug Valley in China, one such cluster. Indias Genome Valley in
Hyderabad is 100 percent occupied. And these are just some of the successful
examples. Taiwan is replicating the success for it first such infrastructure Taipeis
Nankang Biotechnology Plaza across the nation. At least 10 parks will be
operational in Taiwan in the near future. Malaysia, a relatively late starter in the area
too is making progress and in 2008 launched its Triple Helix initiative linking all such
infrastructure in the country.
Some of Biotech Parks in India: Some of Biotech Parks in China:

Bangalore Helix, Bangalore Suzhou BioBay, Suzhou
TICEL Bio Park, Chennai Hong Kong Science and Technology Parks
Gujarat Akruti Biotech Park, Vadodara Zhongguancun Life Science Park
Shapoorji Pallonji Biotech Park, Hyderabad Shanghai Zhangjiang Hi-Tech Park
International Biotech Park, Pune
Kinfra Biotech Parks, Thiruvananthapuram
ICICI Knowledge Park, Hyderabad
MITCON Biotech Park, Pune
Biotech Park, Lucknow
Marine Biotech Park, Visakhapatnam
Agri Science Park, Hyderabad
Biotech Parks in Rajasthan
Golden Jubilee Biotech Park for Women Society, Kanchipuram

BIOTECHNOLOGY IN PAKISTAN
In Pakistan Biotechnology is at a junction, on one side we possess enormous
natural assets but on the other end vast political, social and economic problems
persist. It is evident from the history that the policy makers of Pakistan lack the
political will when it comes to issues in science and technology.
A number of worthwhile programs in natural sciences, health, education and
economic development, had been initiated by the preceding governments, progress
continues to be inhibited by limited financial resources and an incompetent and
burdensome administrative structure. The allocation of financial resources and even
foreign aid among scientific institutions is uneven to the core.
The result being, some institutions have the latest equipment and hardware, while
many others don't even have funds for stationery. In such an environment,
biotechnology and genetic engineering face seemingly insurmountable hurdles.
There are a variety of funding mechanisms now in place to support research and
development in different biotech disciplines in the country and incentives have been
provided to enhance performance. At present there are hundreds of scientists,
working for more than 29 centers, who conduct biotech research in different areas.
(See Annexure -a)
A great number of scientists are being trained through local PhD programs and
through training at foreign universities.
Pakistan today has achieved a unique status in agricultural, health, industrial and
environmental biotechnology. It is appropriate therefore that it should support
research efforts in biotechnology and commercialization of the products developed.
Institutional Infrastructure
In Pakistan the biotechnology program actually started with the establishment of the
National Institute for Biotechnology and Genetic Engineering (NIBGE) at Faisalabad
in 1987 by the Pakistan Atomic Energy Commission (PAEC). This institute has
emerged as an important linkage in the advancement of biotechnology.
However the whole idea about the institute emerged in 1981 when a course on
recombinant DNA technology was organized by the Nuclear Institute for Agriculture
and Biology (NIAB) at Faisalabad. At that time NIAB was one of the three
agricultural centres of the PAEC. The training workshop asked the government of
Pakistan to develop a national centre of biotechnology and genetic engineering. The
Ministry of Education later approved the establishment of a Centre of Excellence in
Molecular Biology (CEMB), to be built on the campus of Punjab University. The

National Institute for Biotechnology and Genetic Engineering (NIBGE) was

approved in 1986. NIBGE was developed by Government of Pakistan with the
investment of US$ 10.00 million.
The government of Pakistan is also supporting some other initiatives such as the
Centre for Advanced Molecular Biology (CAMB) and the Institute of Biochemistry
and Biotechnology (IBB). Recently, an Institute for Biotechnology has also been
established at Karachi.
Although most biotech research institutes assert that they have the ability to carry
out biotech research and development in many fields, only a few have made worth
mentioning achievements. A brief about some of the key centers in the country is:
Nuclear Institute of Agriculture and Biology (NIAB)

The government of Pakistan launched a program under which expatriates visited
different research laboratories and participated in short-term courses and training
workshops in the early 1980s. The Nuclear Institute of Agriculture and Biology
(NIAB), Faisalabad in 1981 organized a course on recombinant DNA methodology
and genetic engineering which was a marked beginning of initiatives in
biotechnology.
NIAB, established in 1972 by the Pakistan Atomic Energy Commission (PAEC), has
a few major achievements which include the introduction of new crop varieties and
studies related to the control of salinity and pests. Pakistans best-known cotton
variety, NIAB-78, which was formulated at this institution, now covers about 50 per
cent of the area under cotton cultivation in the country.
Another variety NIAB Karishma, which gives a higher yield, has shown tolerance to
cotton leaf curl virus (CLCV) disease. Research activities at NIAB are carried out in
different divisions, including those that deal with mutation breeding, entomology,
biological chemistry, biochemistry and natural products.
The institution has well-equipped laboratories. It collaborates with a number of
international research institutions like the International Atomic Energy Agency,
International Foundation for Science, Third World Academy of Sciences and
International Crop Research Institute for Semi Arid Tropics.
The National Centre of Excellence in Molecular Biology (CEMB)

Founded in 1985 the National Centre of Excellence in Molecular Biology (CEMB),
University of the Punjab, now comprises of state-of-the-art laboratories for carrying
out cutting-edge research in molecular biology and biotechnology. Apart from its

research and library facilities, CEMB has land as well as infrastructure for testing
genetically tailored crop varieties.
One hundred and 60 persons, including 31 senior scientists, 10 post-doctoral
fellows, 53 MPhil and PhD scholars, nine technicians and 66 administrative and
para-scientific staff are employed there. It has a total annual budget of about
$500,000.
The institution has to its credit a number of major achievements in modern
biotechnology. It developed plant expression vectors for the introduction of foreign
genes and synthesized four Bt pesticidal genes used in cotton and rice against
American bollworm and rice leaf-folder.
The genetically modified pest resistant varieties produced there include Bt rice
Indica Basmati 370, while three novel Bt genes are being patented through a US
company. Confined field trials of Bt basmati rice were successfully carried out last
season. In addition, studies are being carried out to evaluate virus and insect
resistance in genetically modified crops of mango, potato, tomato, chickpea,
sugarcane, tobacco and cucurbits.
The centre has discovered 45 new restriction enzymes. It has also developed
procedures for the diagnosis of genetic and infectious diseases and is known as a
pioneer in DNA-based methods for pre-natal diagnosis of beta thalassaemia.
On the international scene, CEMB collaborates with the University of Washington,
New England Biolabs, University of Cincinnati and National Institute of Health, USA.
The National Institute for Biotechnology and Genetic Engineering (NIBGE),

Faisalabad, is a federal research institute that was established in 1992. Within a
short span of five years, this centre earned a place among institutions of excellence
in the country. It has been granted the status of an partner centre for the
International Centre for Genetic Engineering and Biotechnology.
There are seven research centres of NIBGE, including plant biotechnology division,
biofertilisers technology division, health biotechnology division, industrial
biotechnology division and environmental biotechnology division. In the plant
research sector, the relationship of Gemini Viruses with cotton leaf curl disease has
been understood at the molecular level and Burewala strains-linked disease has
been tackled by developing ways to differentiate between different viral genomes.
As cotton is the backbone of our economy, the plant biotechnology division focuses
on it. The centre is involved in a project with the John Innes Centre, Norwich, United
Kingdom, and the University of Arizona, USA, through the International Cotton
Advisory Committee, Washington DC.

A bio fertilizer, with the trade name of Bio Power, has been launched for various
crops by NIBGE. It is the first Pakistani institute that has developed diagnostic tools
for various diseases based on the Polymerase Chain Reaction. Bio mining of low-
grade Pakistani ores is another process that's ready for commercial application.
Impact of Biotechnology
After suffering the losses from acute epidemics of cotton leaf curl virus, the
biotechnological interventions have contributed significantly towards sustaining the
cotton production. In addition, development of virus-free potato seed, banana and
micro-propagation of sugarcane through tissue culture are only some examples of
biotechnology benefits in Pakistan. Commercialization of biofertilizers for rice, wheat
and legumes has also come about because of the biotechnology researches carried
out at NIBGE and NARC. According to a study with the introduction of the BT cotton
in Pakistan could result in a 45-55 per cent reduction in insecticide use on cotton.
This would mean a benefit of about Rs. 4 to 5 million, apart from the favorable
impact on the environment and increase in cotton yield. So far, transgenic plants
have been produced in about 60 plant species. Cotton has received special
attention of the biotechnological companies in the developed countries who were
attracted by the profit motives associated with the high value added to the
transgenic seeds.
NIBGE has become internationally a lead centre for research on cotton leaf curl
virus by deciphering the virus genetic code and documenting the genetic diversity
existing in the field. A useful input from University of Arizona, Tuscon; John Imn
Centre, Norwich, UK; Imperial College and Queen Mary College London resulted in
accumulation of useful data, which is now being utilized for developing transgenic
cotton resistant to CLCuV. Similarly establishment of a Plant Genomic Laboratory in
collaboration with PARC (Pakistan Agricultural Research Council) is a step in right
direction. The Institute has also excelled in the area of biofertilizers with support
from IAEA and more recently from Islamic Development Bank through which
Biofertilizer Resource Centre (BIRCEN) has been established at NIBGE.
Commercialization of biofertilizers under the trade name of BioPower is greatly
helping in development of sustainable agriculture.
International Collaborations
Several programs have been initiated and launched in biotech and advanced
molecular technology in Pakistan in collaboration with other countries.

Pakistan has signed an agreement with China for cooperation in the areas like
agriculture, health and industrial biotechnology. Under this agreement, scientists as
well students from both sides will be exchanged at graduate level and postdoctoral
level. Exchange of eminent scientists as teaching faculty to participate in the
academic activities of national universities and institutes will also take place.
Exchange of microbial culture to enhance fermentation technology capability shall
be encouraged. It has also been recommended that joint bilateral symposium
should be regularized on annual basis. The action plan also includes submission of
joint research projects to be reviewed by scientific committees on both sides and
their subsequent implementation. More than 72 projects have been submitted to the
Ministry of Science and Technology by various R&D organizations which will be
screened for undertaking joint research projects under Pak-China joint Research
Fund.
A joint operating arrangement (JOA) worth $10 million for scientists cooperation in
the field of natural sciences has been signed between Pakistan and United States.
The arrangement has been designed for further cooperation among scientists of the
two countries in the areas of significant mutual interest with a focus on collection,
evaluation and exchange of germplasm, plant genomics, plant biotechnology, stress
biology, bio-informatics, application of information technology in agriculture,
identification and control of animal and plant diseases, dry land/sustainable
agriculture production systems, biotechnology/microbiology and agribusiness
development.
Some of the projects selected for joint funding under Pakistan-US Science and
Technology Cooperative Program include: Gene pyramiding through genetic
engineering for increased salt tolerance in wheat; Understanding and control of
plant viral disease complexes in Pakistan; Intensification of forensic services and
research at the Centre for Applied Molecular Biology.
In May of 2005 a meeting was held between Pakistan, India and the US at Lahore.
In this meeting, an "umbrella agreement" on biotech science was initialed which is
the first one with any country in the region. This would serve as an oversight panel
for the tripartite collaborative project on pro-poor and pro-nature agricultural
biotechnology. The main objectives of this include breeding crops for
tolerance/resistance to abiotic stresses with particular reference to drought and
salinity, risk and safety assessment, human resource development in advanced
technologies with particular reference to techniques relevant to the collaborative
research program, and technology sharing in areas of mutual benefit.
Pakistan has also benefited by the Asian Development Bank loan of $905,000 for
the research and cultivation of iron-rich rice. The project duration was from 2002 to
2005.

Islamic Academy of Sciences (IAS) of which Pakistan is also a member, organized

a special session on biotechnology and genetic engineering. IAS adopted a Rabat
Declaration in 2001, urging leaders and decision-makers of the OIC member
countries to divert available resources to science education with a view to building a
scientific and technological manpower-base capable of adapting and developing
new technologies. The member states were also urged to re-define national
developmental objectives in the area of science and technology, especially
biotechnology and information technology, in view of globalization and free trade
arrangements. Equally stressed was the need for OIC countries to introduce
biotechnology programs at various stages of the educational process.
Private Sector Participation

The first generation biotechnology is yet to be commercialized in Pakistan at a large
scale. Practically, all the plant tissue culture (PTC) laboratories are in public sector
and universities. Commercial exploitation remains insignificant despite noticeable
contribution in basic research in PTC technology. Most of the research work
conducted in universities or research institutions has not been developed beyond
laboratory level achievements. This may be due to the fact that mostly research in
Pakistan is based on public funds and is of academic nature. The interest of
research laboratories does not match with those of industry unless preference is
given to applied research at the time of funding. Thus no commercially viable plant
tissue culture laboratory has been established in private sector, all over the country.
However, Agriculture Biotechnologies Pakistan (Pvt) Ltd. is operating in the field of
micro-propagation and seed production since 1995 to achieve the excellence in
high technology agriculture.
In the private sector, Monsanto Pakistan, is one of the active players among TNCs.
It has acquired businesses of Pakistan Cargill Hybrid Seeds, Dekalb Genetics and
Asgrow. Now Monsanto deals with proprietary Corn, Sunflower and Forage
Sorghum hybrid seeds. As part of a commitment, Monsanto is the only multinational
producing and marketing genetically modified seeds. Monsanto has initiated some
work on producing drought tolerant plants. Although the research is in the initial
stages, the results are encouraging. Scientists are working on the project by
sequencing the genes in corn, soy, and rice genomes. Monsanto is confident of
providing drought tolerant varieties, which will also improve the yield. Under severe
water stress tests the productivity of these varieties increased at least two-fold.
NIBGE has also established a private commercial arm. This is called Pakistan
Innovative Biotechnology service (PIBS). The mandate of PIBS is to expedite the

commercialization of technologies applied in various sectors of the industry and

agricultural fields, which might have a direct and indirect impact on economy.
Biosafety framework
The government has ratified or signed many international agreements, like the
Convention on Biological Diversity, Trade Related Aspects of Intellectual Property
Rights, and Cartagena Protocol of Biosafety, to exhibit its growing interest in the
genetically modified organisms trade under WTO rules and regulations. Still the
biosafety regulatory legislation for research and development is in its infancy.
Pakistani research institutes do follow international biosafety regulations, such as
those approved by the US National Institutes of Health. The legal protection for
intellectual property is being strengthened. Regulations to govern and supervise
DNA research and products (Biosafety Guidelines 2005), involving genetically
modified organisms, have been approved by the ministry of environment. Pakistan's
National Biosafety Committee is in charge of ensuring that risk assessment is
carried out in accordance with biosafety guidelines.

POTENTIAL PROJECTS FOR COMMERCIALIZATION
Industrial Enzymes
Xylanase
The paper industry is another old technology that relies heavily on wood, energy,
water and chemicals. New technologies have emerged that are changing the face of
this industry. The pulp and paper industry was estimated in 2000 to be the fastest
growing market for industrial enzymes. Enzymes are quickly replacing traditional
chemicals in pulping, in paper production and in de-inking recycled paper.
Bio-pulping (using fungi) results in a nearly 30 per cent saving of electricity, while
treatment with cellulase and hemi-cellulase reduces wood-drying time considerably.
Bioleaching of pulp reduces chemical requirements by 50 per cent. The use of

enzymes and fungi increases the physical properties of the fibers and the quality of
paper. Many developing countries have lagged behind in technological
developments in paper manufacturing and have become importers of paper, even
when they have the potential to be exporters.
Large amount of lignin and hemi-cellulose are fragmented and solubized during
pulping in paper industry. The remaining lignin hemi-cellulose gives the pulp a dark
color. For whitening of the pulp to required degrees, bleaching chemicals like
Chlorine, ozone, peroxides, chlorine dioxide etc are used resulting in huge
quantities of toxic waste. Xylanase enzyme which acts on xylan (A polymer
containing mainly xylose) is used for pre-bleaching to reduce the amount of
chemicals used and ultimately reduce the toxic waste.
The enzyme Xylanase is produced by Thermomyces species of bacteria. Hyper

production of Xylanase by these bacteria has been obtained at NIBGE for a pilot
project with one of the leading paper industry and the results have shown to have
significant economical benefits
There is ~ 2 degree increase in brightness as compared to the control

A reduction of Kappa no. by ~ 1.7
Xylanase along with NaOCl 4%, 4.5% and 5.5% were used to obtain a final
brightness of 80% of the treated pulp as compared to control pulp
The results show that the Xylanase when used required only 4 % to 4.5 % of
NaOCl, thereby, saving the costs on the chemicals to 25 % (approx.)
The replacement of chemical with enzyme has direct effect on reduction of
toxic release of hypocholrates.

Feasibility determined at industrial scale may provide economic as well as

environmental benefit to pulp and paper industry apart from many other industries
where it is used.
Citric Acid
Pakistan is importing citric acid to meet local demand and spends about Rs.100
million per annum on its import. Demand for citric acid is on the rise. Indigenous
product can substitute or finally replace the imported one. This product will play a
vital role in not only reducing foreign exchange spending but will also give impetus
to local biotechnology expertise.
Citric Acid is used in food industry, confectionary and beverages. Approximately
15% of citric acid finds usage in chemical industry (removal of sulphur dioxide from
flue gases of power stations, metal smelters, metal plating, in detergents, tanning
and textiles) and 10% in pharmaceuticals and cosmetics (solvent and flavoring
agent, effervescent with carbonic acid, antioxidant and synergist).
The raw material is sugar cane molasses and beet molasses which are abundantly
and cheaply available. Steep liquor, a byproduct of starch industry, can be used as
a nitrogen source. Seed culture of Aspergilluss Niger mutant is developed in
glucose medium and serially transferred to larger fermenter to provide 10% (v/v)
inoculum for large scale fermenter (50,000 litre fermenter working volume) in
750,000 litres fermenter. Cells are recovered using drum filters. The acid is
recovered by neutralizing it with lime and heating to 90 C. The acid is regenerated
by treatment with sulphuric acid, decolorized, crystallized and packed for marketing.
This facility can also be utilized for mass production of acetic acid and lactic acid
(for food industry)
At NIBGE, Aspergilluss Niger strains are available and have been extensively
studied for production of citric acid. All conditions have been optimized for hyper
production of this product. Up-scaled fermentation process is needed for mass
production of this product with an estimated total cost of project at Rs. 100 million

Cellulase
We are importing over 500 tons of cellulase to meet the demand of hosiery and
denim units in the country. A significant portion of export earnings from this sector is
spent on the import of cellulase. Indigenous product can substitute or finally replace
the imported one. This product will play a vital role and will not only reduce foreign
exchange spending but also give impetus to local biotechnology expertise.
Cellulase is used in textile technology, feed and fruit juice industry. The raw
materials are wheat straw, wheat bran and other lignocellulosic substrates. These
are our main agricultural residues and are abundantly and cheaply available.
Mineral salts are used additionally. Vegetative inoculum of Humicola insolens,
Humicola grisea or other thermophilic fungi developed in the laboratories, producing
thermo stable cellulose enzymes is used. Glucose medium is transferred to larger
fermenter to provide 10% (v/v) inoculum for large-scale fermenter (50,000 litre
fermenter working) in 750000-litre fermenter. After adding the carbon and nitrogen
sources the electrolyte will add to allow the cells to settle down on the bottom. The
cells are recovered using high-speed centrifuge. The supernatant is sold as
cellulase to local vendors. This facility can be utilized for production of other
enzymes as well.
The requirement is to upscale fermentation process for mass production of
industrial enzymes, initially a-amylase, followed by cellulases, xylanases, proteases
and lipases. Several potent strains are available at NIBGE and have been
extensively studied for production of industrial enzymes. Some of the organisms
were improved by mutagenesis or recombinant DNA technology. All conditions have
been optimized for hyper production of a-amylase and other enzymes. A detailed
feasibility is needed but the approximate cost of the project is expected to be Rs. 60
million
Alpha Amylase
The main targets will be to upscale fermentation process for mass production of
industrial enzymes, initially a-amylase, followed by cellulases and xylanases.
Several potent strains are available at NIBGE and have been extensively studied for
production of industrial enzymes. Some of the organisms produced products with
low titers and were improved by mutagenesis or recombinant DNA technology. All
conditions have been optimized for hyper production of a-amylase and other
enzymes. Further work is needed for production of other products.
Pakistan is importing about 5000-7000 tons of alpha amylase to meet the demand
of textile industry in the country spending > Rs. 700 million annually on import of
this enzyme. This product will play a vital role and will not only reduce foreign

exchange spending but also give impetus to local biotechnology expertise. In

addition to the use of alpha amylase in textile and feed industry, it is also used in
production of high fructose syrup.
The required raw material is wheat bran, a byproduct of wheat flour mills which is
abundantly and cheaply available. Corn steep liquor, a byproduct of starch industry,
can be used as a nitrogen source. Both are easily available and there will be no
scarcity of both media components.
Seed culture of bacillus licheniformis is developed in glucose medium and serially
transferred to larger fermenter to provide 10% (v/v) inoculum for large-scale
fermenter (50,000 litre fermenter working) in 750000-litre fermenter. Electrolyte is
added to allow the cells to settle down on the bottom. The cells are recovered using
high-speed centrifuge. The supernatant is collected as alpha-amylase. The strains
are available at NIBGE. This facility can be utilized for production of other enzymes
and the total cost of the project is estimated at Rs. 100 million
Lysine
Main use of lysine is in food industry and animal feed. Lysine is deficient in cereal-
based animal feed and needs supplementation. Pakistan imports lysine to meet
local demand of animal feed industry. To meet the ever-increasing demand of
lysine, there is a need to indigenously produce the product that can substitute and
finally replace the imported one. Main raw materials are sugar cane molasses and
beet molasses. These are abundantly and cheaply available. Corn steep liquor, a
byproduct of starch industry, can be used as a nitrogen source.
Seed culture of Corynebacterium glutamicum can be developed in glucose medium
and serially transferred to larger fermenter to provide 10% (v/v) inoculum for large-
scale fermenter (50,000 litre fermenter working) in 750000-litre fermenter. Cells can
be recovered using ultracentrifuge. The acid can be crystallized and packed for
marketing. This facility can be utilized for mass production of other amino acids like
methionine (for food and feed industries).
Up-scaling of fermentation process for mass production of Lysine is required.
Corynebacterium glutamicum strain is available at NIBGE and has been studied for
production of Lysine. The mutant organisms will be developed for application in
mass production of this product. All conditions will be optimized for hyper production
of this product. Further work is needed for mass production of this product. The
approximate cost of the project would be Rs.100 million

BioPower
A key limiting factor in crop production is supply of Nitrogen. Chemical fertilizers are
often short in Pakistan or beyond the reach of many poor farmers. However,
biological nitrogen fixation (BNF), the fixing of atmospheric nitrogen by microbes
and making it available to plants, could be harnessed to improve the soil fertility and
productivity of crops (Mekonnen et al., 2002). These microorganisms are often
referred to as biofertilizers. However, biofertilizers also include microorganisms that
solublize phosphorus to make it available for plants (Garg et al., 2001).
Microorganisms like Azospirillum, Azotobacter, Rhizobium, Sesbania, algae and

Mycorrhizae, have the ability to fix nitrogen. P. striata, and B. megaterium and
Aspergillus are among other microorganisms that solublize phosphorus. In return,
the plant provides these organisms with a favorable environment and a carbon
source in a symbiotic relationship. It is this relationship that is critical in seeking to
broaden the use of biofertilizers in association with many food crops. Countries
such as Bangladesh, Brazil, Kenya, the United Republic of Tanzania, Zimbabwe
and Zambia have had successful pilot plants for the production of biofertilizers, and
demand has often exceeded production.
Biopower developed by NIBGE with a successful commercial production at their

pilot plant presents an excellent opportunity to enhance the crop yields of our
farmers. This could provide an affordable source of agricultural inputs, especially in
rural areas where resource-poor farmers cannot afford the chemical inputs.
However NIBGE failed to increase the sales rather could not sustain the initial
successful sales due to lack of marketing and sales expertise or a commercial
department. BioPower can be easily produced locally and the technology needed to
produce it is not complex.
It is estimated that about 3 to 4 million rupees are required to build a 100-150 metric
ton Biofertilizers plant. Alternatively, 40 million for 10 plants in different locations
could produce up to 1000-1500 MT to meet the demand by rural farmers.
Biofertilizers have a market locally and possibly internationally with increased
production capacity.

Human Healthcare Vaccine & Biopharmaceutical Development

Good health defined in terms of state of complete physical, mental and social well
being is a prerequisite for a nation to be productive. This is because ill health not
only covers disease but also hunger, exclusion, isolation, insecurity and
powerlessness which consequently prevent individuals from realizing their full
potential. Good health, in contrast is not only valued in its own right, but it also
raises the human capital of a country, thereby positively contributing to the
economic and social development.
Maternal and infant mortality remains high as is the population growth rate.
Pakistan has grown much more than other low-income countries, but has failed to
achieve social progress commensurate with its economic growth. Meeting the vision
embraced in the Millennium Development Goals by 2015 (including the reduction of
infant and child mortality by two thirds and maternal mortality by three quarters and
halving the percentage of the population living in poverty) will require renewed
efforts in Pakistan.
Vaccines are important tools in disease prevention programs and their availability at
good quality and at affordable cost represents a challenge for health systems,
particularly in developing countries. New global changes and challenges, including
increased competition, difficulties in accessing cutting edge technology, reduction in
the number of vaccine suppliers, limited market and profit margins and decreased
interest in vaccine production by the industrialized countries, are putting additional
strains on self-sufficiency initiatives. The multinational manufacturers who have
traditionally supplied a large proportion of the vaccines to EPI, which targets the
killer diseases of childhood, are now diverting their business to more profitable
products. This move has created a void for EPI vaccines, which is being filled by
manufacturers from developing countries. In 1992, 100% of the vaccines purchased
by UNICEF came from the industrialized countries; in 2000, 53% came from
developing countries. 65% of all BCG vaccine and 56% of all measles vaccine
produced globally are manufactured in India and Indonesia. These factors have
direct and great implication for the policy makers in Pakistan. The incidence of
earthquake in 2005 exposed our vulnerability to the critical availability of life saving
vaccines and biological like anti Tetanus serum.
THE VACCINES SITUATION IN PAKISTAN

The vaccines are classified in a variety of ways;
Vaccines for use in human or for Veterinary or Poultry use
Pediatrics v/s Adolescent and Adult vaccines

Bacterial, Viral or other Microorganism target vaccines

Regular v/s Emergency response vaccines like Anthrax, Small pox
Therapeutic v/s Preventive vaccines
A quick look on the market side will focus the attention to the market forces which
determine the commercial issues adversely affecting this market
The size of the global vaccine industry is close to US$ 10 Billion in 2007-8. A few
multinational manufacturers dominate this market like GSK, Novartis and Sanofi
Aventis. The growth rate of the vaccine market is faster than the Global
Pharmaceutical market but it is risky and challenging. The growth rate is good in
contrast to the slow activity witnessed in eighties.
In Pakistan, almost 80% of the vaccine market is with the public sector. Based on
IMS data the total size of the private vaccine market in Pakistan is estimated at Rs 1
Billion annually. This is a small fraction of the annual market size of Rs 105 billion
for pharmaceuticals. It is thus readily apparent that without a concerted effort it will
be difficult to get the Vaccine industry off to a jump start in Pakistan as the market is
neither considered sizeable nor financially lucrative.
In the private sector there are several multinationals operating such as Glaxo Smith
Kline (GSK), Aventis (through Sind Medical Stores), Wyeth and Novartis. Only one
national company Amson Vaccines is doing some value addition steps in vaccine
manufacturing.
Vaccines for public health use in Pakistan were largely imported through UNICEF
procurement systems. Although NIH has vaccine production facilities, there has
been erratic supply of EPI vaccines through this system and has provided some
vaccines to the EPI over the past few years, it is estimated that about 90% of all
vaccines were imported by direct purchase or through UNICEF.
The National Institute of Health is a premier research organization in the field of
public health. The institute acts as the research arm of the Ministry of Health and is
a WHO collaborating center for research in viral diagnostics. Its Biological
Production Division manufactures bacterial and viral vaccines and therapeutic anti
sera. Vaccines are being manufactured both from raw material i.e. "Basic
Manufacture" and through "Production Sharing" i.e. buying of bulk concentrates and
processing for filling and packaging into final containers.
Present failure of NIH in vaccine production can largely be attributed to its inability
to invest in research and development which is essential for the indigenous
development of raw materials (seed virus, seed bacteria, culture media etc). For
sustainable and self reliant vaccine manufacture such facility is the need of time. To
restructure and reorganize Biological Production Division to run as a commercial
organization with corporate culture is the only solution.

Therapeutic Proteins - Interferon

National Program for Prevention and Control of Hepatitis was launched in 2005 as
the Prime Ministers initiative, the program was a response to the high prevalence of
hepatitis B and C (estimated at 3 % in the general population and 5-22 % in the high
risk group). The program focuses on mandatory vaccination of all children less than
one year of age, vaccination of high-risk groups, promotes safe blood diffusion,
disposal of syringes, sterilization of medical devices and availability of safe water
and disposal of sewage. Currently the baseline for this program is being
established.
New PC1 worth 11 billion rupees for next 5 years has been approved for the
National Hepatitis Program with emphasis on increased share for treatment of
Hepatitis as compared to 2.59 billion rupees of the last 5 years which had major
share for diagnosis and prevention.
Interferon:
The current market of Interferons in Pakistan is valued at Rs. 2.4 billion according to
IMS with an average 10% growth rate over the last 3 years. The market is expected
to grow @ >10% per annum for next 3 5 years. The prescription / Institutional
sales ratio is approximately 30:70 whereas IMS gives the prescription data only.
Several low priced Chinese brands are coming in the market leading to strong price
competition. At the same time increasing exchange rate is resulting in lower
margins for importers of finished products.
Hepatitis disease incidence will keep on increasing especially Hepatitis-C. The
change in disease pattern i.e. increasing resistant serotypes is leading to increased
period of therapy required as compared to 24 months. This means that the demand
for the product will keep on increasing.
CEMB Lahore has developed a process which requires less quantity of fermenter.
The product is ready for finishing and formulation on commercial basis at some
GMP compliant sterile facility.

Project Kick-Off
Technology Transfer
Bio-Process Chart Cell Line Development

Screening & Selection
Process Development
Fast-Tracked Process Development
Upstream
Downstream
Virus Clearance Studies
Scale-up studies
Characterization of Purified Protein
Generation of Toxicology Material
Method Development
Method Qualification
Process Transfer to GMP Production

GMP Documentation Preparation
GMP Production
Master & Working Cell Banks Generation
Production of Bulk Drug Substance
Primary Formulation
Q C Test
Q A Release
Stability Studies
Regulatory Support
CMC & Quality Data Preparation
Support for IND & BLA, EUDRA, CTA & MAA

Animal Healthcare Vaccine development

Veterinary Vaccines:
This is one of the most important segments in Vaccines. Its economic impact is
comparable to human vaccines. A series of workshops were conducted under the
COMSTECH, HEC and USDA. This can revolutionize the social sector in Pakistan.
The Indian example is a good model. A multinational group Merrial of France tried
to have a Public Private partnership with Punjab government to manufacture Foot
and Mouth Disease vaccine but could not materialize due to unknown factors.
Current status of vaccine production in the veterinary sector
In the year 2006, six institutes of the country produced over 32 million doses of
vaccines against five bacterial diseases. Similarly for same period and from same
institutes, over 282 million doses of vaccines against nine viral diseases were
produced. The six institutes producing these vaccines include
1. Veterinary Research Institute Lahore
2. Veterinary Research institute Peshawar
3. Veterinary Research Institute Quetta
4. Sindh Poultry Vaccine Center Karachi
5. Nuclear Institute of Agricultural Biology Faisalabad
6. Poultry Research Institute Rawalpindi
Almost 95% of vaccines against large animals are produced locally in public sector
institutes and only Foot and Mouth disease vaccine is currently imported. Recently,
few private entrepreneurs have also started to produce vaccines but only in limited
quantity. The data from 2006 indicate that over 2 - 3 million doses of different
vaccines have been produced in the private sector.
Despite the aforementioned capacity the local needs for animal vaccine far outstrip
existing capacity. For more than 105 millions cattle, buffaloes, sheep and goats the
country is producing only slightly over 32 million doses of vaccines for five different
bacterial diseases. It is reported by the Livestock Departments of all Provinces that
only 5 to 10% animals are vaccinated each year.
The foot and mouth disease for cattle (a source of great economic loss in the west)
is causing heavy losses every year and a large quantity of vaccine against this
disease is being imported from France and Iran. There is urgent need to develop a
high quality vaccine against the strains of Foot and Mouth disease causing virus
prevalent in Pakistan. Development of DNA Vaccine is most appropriate option.
Domestic Poultry is not fully vaccinated, however all commercial poultry farms are
hundred percent vaccinated against the viral diseases. The Breeders flocks do not
use local vaccine to avoid vertical transmission of virus. It is estimated that poultry
vaccines worth of 1.2 billion are imported every year. There is urgent need to have

Specific Pathogen Free Eggs production facilities in the country for the production of
better quality vaccines. Biotechnological Interventions can be very effectively used
for production of better quality vaccines for poultry diseases to capture ever-
increasing demands for all types of poultry vaccines.
All vaccines for the infectious disease of Dogs and Cats are imported. VRI Lahore is
producing Anti-Rabies vaccine for dogs in limited quantity but it is not well accepted
by the dog owners. They preferred imported vaccines. It is estimated that every
year 0.2 million doses of Rabies vaccine for dogs and cats are imported. To control
Rabies, compulsory vaccination of all dogs and cats is required. Biotechnological
intervention is essential to produce good quality local vaccine for mass vaccination.
Vaccine development for Foot & Mouth Disease (FMD)

Pakistan is said to be an Agricultural Country where agriculture contributes about
21.6% to the GDP/GNP. Out of this the share of livestock is 49.6% or in other words
livestock contribution to GDP/GNP is around 11%1. Contribution of Livestock is
8.0% in the Total Exports of Pakistan. Average household holdings are 2-3
cattle/buffalo, 3-4 sheep/goats and 10-12 poultry per family which contribute 35 to
40 percent of their income.
Animals provide food (meat, milk, milk products and eggs) for domestic
consumption and sale; hides and skins, which are essential inputs to the country's
leather industry ; wool and hair for textile and carpet industry; and, a range of by-
products, including manure and bone meal. Animals also have a vital role in
providing traction for cultivation and transportation.
The strategic location of the country and potential of livestock sector creates a good
export avenue for our livestock and livestock products. The major exports include
animal casings, bone and its products, animal wastes, live animals, meat, dry milk,
wool, hair, feeding stuff for animals and poultry.
According to latest statistics, Pakistan is the 4th largest milk producing country in
the world with an estimated 30 (available for human consumption) million tons of
annual milk production from 50 million animals. These animals are managed by
approximately 8 million farming households. The rural urban share of this milk
production is 71 vs 29%. Only 3% of the total production of milk is processed and
marketed through formal channels.
Despite immense potentials, the dairy sector in Pakistan has been victim of criminal
neglect by the successive governments in the country. Even at its present lowest-in-
the-world yield per milk cattle, Pakistan is hugely surplus in milk productions but due
to lack of proper planning, collection and distribution facilities, a major portion of the
total production is consumed, per force, by the producer in the far flung areas. As

against this we are importing about 25000 tonnes of powder milk annually to meet
the demand of the urban areas at a cost of above 400 million dollars.
It is an untapped market with a huge potential for growth which can bring about a
dairy revolution in the country, creating new jobs and improving the poverty
situation. Unfortunately at present the dairy sector of the rural economy is not
making a significant impact in the national economy in accordance with its potential.
This is because of old and traditional dairy farming practices, poor infrastructure in
rural areas, lack of contact for farmers to the market mechanism, lack of knowledge
about optimal feed, lack of a cold chain to protect milk quality, adulteration and lack
of access to well trained support service staff such as veterinarians and vaccination
to protect against bacterial and viral diseases. .
In Pakistan the meat supply can be categorized into Poultry and Red meat
segments. The poultry segment is fairly established and modern farming methods
are being applied, although a lot of areas for improvement can be identified. On the
other hand the existing red meat production system is both traditional and
inefficient. Beef mostly comes from the end of career i.e old animals, or emergency
slaughtered animals. Mostly 1 2 week old baby buffaloes and calves are
slaughtered, only a few are raised up to 60-80 kg and that also on poor and
unbalanced diet.
Large scale cattle farming and formal meat sector is practically non existent in
Pakistan except for one or two meat processing plants. Majority of the rural
population is engaged in livestock farming, having 2 to 5 cattle/buffalo, 5 to 6
sheep/goats and a few chickens per family. Generally, traders purchase old weak
and culled animals from the rural areas and sell them to animal markets in urban
areas. Butchers prefer to purchase these animals and slaughter them in slaughter
houses. Butchers dominate the meat market both in rural as well urban areas.
Even with this state of affairs the livestock contribution in total exports of Pakistan is
8%. Considering the huge potential and implementation of Prime Ministers Special
Initiative for Livestock, the situation is expected to change for better. Prevention and
control of animal disease with better veterinary services and provision of quality
vaccines and medicines at affordable prices is one of the key elements of this
policy.
Foot & Mouth Disease (FMD)
Foot and Mouth Disease (FMD) is a highly contagious, notifiable disease of cattle,
sheep, pigs, goats, other farmed mammals and wild ruminants, and is one of the
most important diseases of livestock. It can occasionally infect people but is not a
significant health hazard.

Seven distinct serotypes of the virus have been identified. The clinical signs of FMD
are similar to several other vesicular diseases and confirmation of diagnosis can
only be made following laboratory tests. On introduction to a herd or flock the virus
can spread very rapidly by direct and indirect transmission. Affected animals have a
high temperature, which is followed by the development of blisters chiefly in the
mouth and on the feet. However, in some species (notably sheep and goats), the
disease is frequently less severe or occurs as a sub-clinical infection. The disease
is not usually fatal in adult animals, although many young animals may die.
However, it causes severe pain and distress, especially in cattle; animals may be
left permanently lame and the productivity of recovered animals may be reduced.
The last outbreak of FMD was in 2001 in the UK where 2,030 farms were affected
between February and September with an estimated loss of 3.1 billion to
agriculture and food industry.
In Pakistan, economic losses are estimated to the tune of six billion rupees per
annum (Zulfiqar 2005) or a loss of Rs 566,000/- per 1000 animals. This does not
include the costs of animal loss.
Prevalence of FMD in Pakistan
Punjab 10 54%
Sindh 12 34%
NWFP 19.4 37.3%
Balochistan 3 70%
AJK 7 31%
Participating Disease Search Data
Mortality rate is 3 5% in adult animals but in young calves it is 15%
FMD Serotypes in Pakistan
A, O, and Asia-1
Two types of inactivated tissue culture FMD virus strains O, A and Asia-1 vaccines
are available. One is Oil adjuvanted and the other is adsorbed on Aluminium
Hydroxide
Dosage regimens is different for both the types
Vaccine availability & usage
o Trivalent vaccine is available in Pakistan. It is manufactured locally mostly by
VRIs and also imported by different importers.
o FMD vaccine is used only on need basis due to:

o Lack of awareness
o Poverty
o Informal farming sector
o Epidemiological-based priorities
o Lack of infrastructure, funds, manpower and commitment
o No Vaccination Strategies
Potential for FMD Vaccine
Current
Animal population 137 million
Dosage requirement per animal 2
Total dosage requirement - 274 million
After 10 years
Animal population 178 million
Dosage requirement per animal 2
Total dosage requirement - 356 million
Current Usage and Sales
In Pakistan 70% ordinary farmers who own less than 5 animals have no awareness
of FMD and do not use any vaccines. However the awareness of FMD is increasing
in the rural farming sector because of the production losses and market orientation.
These are mostly small rural farms and milk farms around cities. In Pakistan
vaccination is done only in cattle and not sheep / goats.
Veterinary Research Institutes at Lahore, Peshawar and Quetta, produce only
300,000 doses of FMD vaccine. These are public sector research institutes with
very limited capacities and produce these vaccines by old methods. Imported
vaccines are expensive and are only used in big farms
Strategies to increase the usage of FMD vaccine in Pakistan
Availability of low cost high quality vaccine for local serotypes
Local manufacturing
Govt. procurements
Awareness campaigns in rural areas for small farmers
Cold Chain facilities

Public/private partnerships for vaccine manufacture

At present the vaccine production & regulation in Pakistan is not capable of
producing vaccines of acceptable quality, efficacy and international standards. The
public sector production / formulation standards for human & veterinary vaccines
are far below the minimum acceptable international standards.
Vaccine production and marketing are most sustainable when undertaken in some
form of commercial environment. In developing countries, experience has shown
that neither relying on purely market forces nor on governmental production and
free distribution of vaccines in total disregard of commercial practices is sustainable.
Vaccine production and distribution in a conventional governmental department
setting tends to focus on the number of doses; it often does not adhere closely to
good manufacturing processes or quality assurance programs and there is little
focus on return on investment and/or technology renewal. Consequently, there is a
tendency to persist with out-dated technology, and little effort is made to ensure
purity, efficacy, or potency of the product.
Almost invariably, government-led production does not target the export market
because of the need to meet demanding quality standards, so all that remains is the
non-lucrative domestic market. By contrast, the private sector will only concentrate
on those vaccines that guarantee high profitability. So there is an increasing need in
developing countries for public/private partnerships for vaccines production.
Similarly, in Pakistan public/private partnerships would be valuable for vaccine
production. For any partnership to flourish there needs to be either a convergence
or complementarities of interests and objectives. Government objectives for
vaccines revolve around national animal health programs and the need for quality
assured vaccines that are affordable, efficacious and safe. The objective for vaccine
production companies is to generate profit from the sale of vaccine.
Where there is an assured high volume demand for particular vaccines there is
good incentive for the private sector to invest in vaccine manufacturing plants, since
it is reasonably certain that they will recoup their investment. Governments role
should be to regulate and ensure the quality control of the end product and monitor
the efficiency and efficacy of vaccine use, rather than involve in production
themselves.
It is suggested that the Public /Private partnership be complementary, as the
government requires a sustained supply of efficacious and affordable vaccines from
the private sector, while the private sector should be satisfied to have a
government-guaranteed demand.

Vaccine development for Egg drop syndrome (EDS) Oil emulsion (Poultry
Vaccine)
Egg Drop Syndrome (EDS) oil emulsion vaccine is effective against egg drop
syndrome in pullets and layer commercial flocks. It maintains the egg production in
layer flock. This vaccine is used in Pullets at the age of 14 -18 weeks, preferably
before laying. Route of this vaccine is intramuscular or subcutaneous. The use of
multivalent vaccine as ND + IB + EDS oil emulsion is very common.
The vaccine is not produced locally and has substantial demand by the layer
farmers. They are forced to purchase imported vaccine on very high price. The
process has already been developed by the Sindh Poultry Vaccine Center (SPVC).
A joint venture strategy can be worked out. Data needs to be established to work
out the feasibility of this project. The establishment of this project would also save
substantial foreign exchange and the vaccine would be made available to the
farmers at a much lower price.
Raw material is available in local market except that identification of etiological
agents of a local strain needs further research. Total cost of the project including
plant and machinery is approximately Rs. 2.5 million

PRODUCTS AVAILABLE FOR COMMERCIAL

PRODUCTIONS
Center of Excellence in Molecular Biology (CEMB), Lahore.

Products: (Products ready in laboratory for marketing)
Product Segment / Industry
Disease Free Potato (Agriculture)

Disease Free Sugarcane (Agriculture)
Transgenic Basmati (Agriculture)
Transgenic Cotton (Agriculture)
Bt biopesticide (Agriculture)
Interferon/Pagylated Interferon (Pharmaceutical)
Kit for detection of HCV genotyping (Diagnostic, Health)
Kit for the detection of TB (Diagnostic, Health)
Kit for the detection of Typhoid (Diagnostic, Health)
Kit for the detection of HBV (Diagnostic, Health)
Kit for the detection of HCV (Diagnostic, Health)
Taq Polymerase
Insulin (Pharmaceutical, Health)
Nuclear Institute for Agriculture and Biology (NIAB),

Faisalabad.
Veterinary Vaccines (Livestock, Poultry)

I. Hydropericardium syndrome (HPS)
II. New Castle virus (NDV)
III. Haemorrhaegic septicemia (HS)
Multi-nutrient Feed blocks (Livestock, Poultry)
Radioimmunoassay (RIA) (Livestock)

Karachi Institute of Biotechnology & Genetic Engineering,

(KIBGE) Karachi.
Alpha amylase from Bacillus subtilis (Industrial Processes - ethanol)

(KIBGE-HAR & KIBGE-HAS)
Proteases from Bacillus subtilis (Pharmaceutical, Food, Detergent)

(KIBGE-HAS)
Dextransucrase from Leuconostoc mesenteroides (AA1) (Pharma, Food, Cosmetic)
Alkaline Phosphatase from Bacillus subtilis (Diagnostics)

(KIBGE-HAS)
HEJ Research Institute, Plant Biotechnology Section, ICCS,

University of Karachi.
Virus free Banana Plants (Agriculture)

Orchids as a Cut-flower (Commercial Agriculture).
Institute of Industrial Biotechnology, GC University Lahore.

Enduglucanase (Textiles)
L-Lysine (Chick Feed)
Alkaline Protease (Leather)
Glucose Oxidase (Diagnostic Kits)

PCSIR Laboratory Lahore

PCSIR BIO-PRO ZINC BACITRACIN (Livestock, Poultry)

(Feed grade antibiotic)
National Institute for Biotechnology & Genetic Enginnering

(NIBGE)
IBD 4: Production of alpha amylase (Textile and Feed industry)

Bio-processing of Ores (Mines)
IBD 2: Thermo-stable celluloses & xylanase (Poultry feed industry)
IBD 1: Development of thermophilic yeasts (Industrial ethanol production)
IBD 3: Pilot and industrial scale production of methane from agro industrial waste
BTD 1: Biodesulfurization of High Sulfur Pakistani Coal by Heap Leaching
PBD 4: High Yielding Pak Upland Cotton Varieties: NIBGE-2 and NIBGE-115
Veterinary Research Institute, NWFP, Peshawar

OIL Adjuvant Haemorrhagic Septicaemia Vaccine. (Livestock)
University of Veterinary & Animal Sciences, Lahore

Foot & mouth Disease (FMD) Vaccine. (Livestock)

RECOMMENDATIONS OF THE CONSULTANT

Since biotechnology is a discipline with great potential, the government's role is of
vital importance so that biotechnological tools could be used safely and effectively
for the benefit of the masses and at the same time safeguard the health of the
commons.
In general the government should:
Formulate clear polices
Provide adequate funding
Formulate and enforce intellectual property rights
Enhance cooperation amongst different ministries & departments such as
o Ministry of Science & Technology
o Ministry of Health
o Ministry of Food, Agriculture & Livestock
o Ministry of Commerce
o Ministry of Industries
o Ministry of Law
Enhance cooperation with the private as well as public sector in the
development of biotech products and services
Enforce biosafety rules to minimize risks
Give equal status to all biotech institutions and scientists
Develop Biotechnology Parks in major cities
Establish a Department of Biotechnology
Commercial Development
Provide support services
Establish Technology incubators
Involve SMEDA to
o Provide free feasibility reports
o Develop Business plans for commercialization
Involvement of Ministry of Commerce and Ministry of Industries
Involvement of FBR for tax holiday
The commercial release of new products must be regulated

Incentives and protection initiatives in various combinations

o Tax Rebates and special tax holidays
o Sharing financial burden of technology transfer rights, royalties etc.
o Loan on soft terms
o Special incentives for export business
o Training incentives to technical staff
Active Public-Private partnerships must be promoted
Fast track approval for biological registration and a preferential treatment for
regulatory support
Research and Education

It is envisaged that a technological base is critical for future research and
developments in the fields of biotechnology. This requires an investment in
strengthening the science base and training of a work force in key areas such as
microbiology, immunology and molecular biology. In addition, biotechnology
projects and training programs must focus on training individuals for future research
and development needs and markets.
HEC to give preference to applied research projects
Establish commercial wings of research institutes / universities
Establish Focus groups in different industries to take up pilot projects
Permanent department for Academia Industry linkage
Monitor to avoid overlapping research
Establish Centralized data base with free access to all
Establish Life Sciences Parks
Capacity-building: Determining the needs
The biotechnology industry development flourishes on solid scientific foundation.

Therefore, assessing and building strong scientific and entrepreneurial bases is
important. Innovations are driven by many factors such as passion, profits and
excellence. The lessons from developing countries and countries with economies in
transition that have built significant capacity in biotechnology can help us to prepare
a model to develop our biotech industry which meets our local needs.

Setting research priorities
Biotechnology is a diverse field in its application and multiplicity of procedures in

each given area. Therefore, research priority setting is important though difficult in
the face of limited resources and manpower, and overwhelming conflicts of
interests. Research priority setting gives both a focus and benchmarks to be
attained. This approach increases specialization. Countries have used this
approach to create institutions whose research area is limited to one crop (e.g.
three cassava research centres in Zambia), one animal disease (e.g.
trypanosomiasis research facility in Kenya) or one objective (e.g. vaccine production
institute in Cuba).
The process of research priority setting should be legitimate and fair. Similarly, the
research priorities may have to be acceptable if they have to gain support. More
importantly, the goals should seem reasonable and justifiable if the projects will
have to be funded. The aim in setting research priority should be to help achieve
some depth and avoid rediscovery of what is readily available.
Often, scientists and their institutions conduct research based on assumptions built
on current knowledge. New development could often change the objectives. For
example, if vaccine development is the main aim and then promising leads for new
drugs development are overlooked, the benefits of an effective drug may be lost if a
vaccine is not developed in time. Therefore, priority setting should not supersede
the need for flexibility to pursue promising leads. At the same time new
development should not overshadow the original goal.
In United States small biotechnology firms developed transgenic crops to generate

resources to finance development of pharmaceutical products which take a long
time to bring to market (Schimmelpfennig et al., 2000). We can adopt a similar
strategy and focus on biotechnology development niches which can provide
significant short-term returns to the national economy. The experience gained
during this process may lead to development of more sophisticated tools, products
and services. Brazil's genomic power was developed in a short period of time by
combining the genomic and information technology to develop virtual genomics
institutions. In the three-year life of its centre, Brazil has contributed more than a
million human expressed sequence tags (ESTs) and three whole organism
genomes; this makes it one of the most productive genome sequencing and
analysis centers in the world.
The case of industrial and environmental biotechnology in the Islamic Republic of

Iran is another example of priority setting. Industrial and environmental
biotechnology was placed above food and medical biotechnology but below

agricultural biotechnology. Iran as an oil producer is likely to derive greater benefits

from industrial and environmental biotechnology due to the structure of its economy.
The Biotechnology Centre of the Iranian Research Organization for Science and
Technology (IROST) has five research areas, of which two focus on application of
biotechnology in processing and engineering, and on environmental remediation.
Health-related biotechnology research priority setting
The potential of biotechnology-related tools for improving the health of mankind is

high. However, meeting the health needs of the millions of Pakistanis is a challenge.
Pakistan does have enough human, institutional and reasonable financial resources
to meet the investments required in order to participate in biotechnology research.
It is important to select the tools that could be used to meet the research priorities.
The tools may be selected on the basis of their ability to make a significant
difference in improving health, address the most important issues and meet
objectives within a realistic time frame. Technologies may also be selected on the
basis of their ability to create new knowledge, economic implications and social
acceptability. Diagnostics, recombinant vaccine and drug / vaccine delivery
technologies should be among the top three.
Assessing national biotechnology capabilities
The assessment of national capabilities in biotechnology is an important step for

developing countries. It also fulfills the requirement of the Cartagena Protocol on
Biosafety. This assessment can also help policy makers, funding and investors in
mapping out biotechnology development plans. A number of countries have used
public institutions, private companies, regional and international centers and
combinations of the four to foster biotechnology development with the aim to
accelerate delivery of products and services to the market place.
The changes in developed countries that have occurred in the biotechnology

industry provide lessons for us as well. The earlier acquisition of biotechnology
start-up firms by large ones in the 1990s has been followed by mergers and spin-
offs of specialized units. A complex network of firms and research institutions has
developed, each providing a specialized service leading to increased outsourcing. If
those with developed financial bases are abandoning the all-in-one model, we need
look in to the possibility of adopting this model to maximize returns on the national
investment.

Human resource development
One of the key determinants in biotechnology development has been identified as

the availability of human resource. The dawn of the US biotechnology industry has
been associated with presence of individuals gifted with intellectual capital (Zucker
et al., 1994). The wealth of scientists with intellectual capital and the flexibility in
interaction between academia and industrial clusters accelerated the growth of the
biotechnology sector. The strength of basic research capabilities seems to be a
determinant in biotechnology or genetic product design and development
(Henderson et al., 1999). Many countries have combined local training programs
with international training opportunities. For example, the Department of
Biotechnology in India initiated a program to train at least 500 graduates a year at
post-graduate level in biotechnology. There is no dearth of biotechnology
institutions in Pakistan which are producing capable scientists, only the need is to
give them a focused direction for applied research.
Financing biotechnology development
Pakistan lacks mature venture capital markets and investment in biotechnology is

viewed as risky and the opportunities it provides seem unclear due to non
availability of authentic data on market sizes. Alternative methods are needed to
help finance biotechnology development at all levels. Investments in research and
development activities are very difficult to obtain even in developed countries.
Government programs are usually the main sources of finance for research
activities.
To overcome this snag of deficient funding for institutional development

(infrastructure and personnel development), some Governments have formed
biotechnology venture capital firms (e.g. Chrysalis Biotechnology and Bioventure in
South Africa) or provided direct finances to the institutions (e.g. Republic of Korea
and India). It is difficult and expensive to build one state-of-the-art facility to meet all
the biotechnology needs. Alternatively we could use universities and other such
centers for research purposes and industrial partners for development, production
and marketing requirements as long as regulations clearly stipulate the
relationships, benefits and privileges of the various players.

Managing capacity development
Development of entrepreneurs is equally important in biotechnology. In many

developed countries, technology transfer offices are now available in most research
facilities operated by universities, non-profit and government funded institutions.
They identify inventions, determine the value, define protection of inventions and
suggest alternatives to commercialization. These efforts help to elevate the profiles
of the institutions, open up new sources of funding and leverage the institutions'
bargaining power. Similar mechanisms can be developed in our research centers as
non of these have well established technology transfer, management and marketing
systems. Biotechnology in Pakistan is generally treated as research tool rather than
an industry. Therefore, the policy makers do not see biotechnology as another tool
in their efforts to industrialize.
Regulatory capacity development
The biosafety regulations have been developed in Pakistan but are still in its
infancy. There is a need to establish monitoring bodies who can implement these
regulations in true spirit. Weak regulatory regimes may lead to indiscriminate
distribution of biotechnology products, while a strict regulatory regime may hinder
technology transfer, adoption and development. The Convention on Biological
Diversity (CBD) emphasizes the need to balance the risk and benefits of modern
biotechnology products and services.
Still the development of intellectual property regimes has remained contentious in

our country. There is a growing recognition of the need to balance protection to
encourage innovations, public access to advanced technology and protection to
conserve traditional knowledge. Protection of traditional knowledge remains largely
undefined. There may be need for harmonization of local regulations to meet the
minimum international norms to enhance trade and development of biotechnology
products and services. We need to develop strong and trusted regulatory regimes
that are transparent enough to dispel suspicions, especially in the wake of
bioterrorism and abuse of intellectual property, be it traditional or modern.
Technology acquisition and diffusion capacity
The three stages of technological development include development of capabilities

to operate production efficiently, create new production systems and produce novel
products (Dahlman et al., 1985). Technology development also involves application

of foreign technologies in production, incorporation of technology by diffusion and

adaptation and improvements of the technology by local experts (Kim, 1980). This
suggests that we need to accumulate foreign technology to enhance production and
then improve its performance to achieve greater efficiency. Finally, the technology is
mastered to facilitate production of novel technological capabilities.
Unless our industrialists can anticipate the benefits associated with the technology
and have a solid scientific foundation backing, it is not likely that they will take a
biotechnology route. Legal and financial incentives may have to be used to
encourage firms to acquire new technologies.
The purchase of transgenic seeds or recombinant vaccines does not constitute

technology transfer per se. It is the acquisition of biotechnological capabilities, such
as fermentation technologies, that constitutes technology transfer. These
technologies are often proprietary knowledge and constitute competitive advantage.
This is the knowledge that firms in developing and developed countries are
interested in acquiring. Countries such as India that already had a relatively strong
pharmaceutical manufacturing base could easily reconfigure it to meet the needs of
biopharmaceutical production processes. They only need to broaden or streamline
their operation, such as production, engineering and marketing structures.
It is obvious that building capacity to absorb, diffuse and establish new technologies
is complex and expensive. However, there are alternatives to the traditional
technology transfer models. The use of public institutions such as universities and
research centers to acquire, adapt and diffuse new technologies through the use of
interactive teams has played a very important role in development of the
biotechnology industry in developed countries. Many universities and research
institutions in developed and some developing countries have built incubator
facilities and technology transfer offices. Incubator facilities nurture inventions into
innovations that could be marketed. Industries in Pakistan do not carry out research
and development activities. Such industries are unlikely to acquire new inventions
or innovations. Incubator facilities could help bridge this knowledge gap by bringing
industry, government and research centers to forge a common front.
Government may also offer incentives that bring competing members of the
innovation system together. These could include tax incentives for industries willing
to invest in university research and increased funding for research teams working
with the private sector. Such incentives will increase access to technology and
promote commercialization.
It is gratifying to note that most of the biotechnology research in Pakistan is taking

place in universities and centers of excellence, it is important to bring the private

sector and the government programs to these research facilities. New approaches
to overcome barriers to technology transfer and diffusion could include economic
incentives to encourage local private sector participation in biotechnology
development and seeking out opportunities for partnerships between the public
sector and private sector and ways of utilizing knowledge and skills of nationals
based in other countries. India is one country that already uses the above initiative.
Government can also trade technology for resources and market access in a win
win situation. Agreements with firms exploiting some of the local resources should
include local capacity-building. The technologies in such agreements should be
acceptable to both parties. Such agreements do not necessarily need to be within
the same field of biotechnology.
International alliances for capacity building
One of the most significant developments in the global biotechnology industry is the
development of networks involving partnering activities. These networks are
products of complex inter linkages between a wide range of enterprises, links which
are designed to reduce the risks associated with the development of new products,
as well as to facilitate information exchange. More specifically, these partnering
arrangements help to provide sources of financing through licensing and upfront
fees for R&D expenses, reimbursement of expenses for partnered products and
services, royalties, profits and other success fees associated with the achievement
of certain milestones. Such arrangements are particularly important in areas with
limited access to other forms of financing, such as venture capital. Even where
venture capital is available, these arrangements still serve an important risk-
reducing function. Partnering activities are naturally more concentrated in the
industrialized countries, but these arrangements are being extended to developing
countries, especially in agricultural biotechnology. In addition to the risk-reducing
benefits outlined above, partnering arrangements could also play a key role in the
development of technological capabilities in the firms and institutions in developing
countries. Such capacity would be specialized and related to specific products and
services. In biotechnology, especially pharmaceuticals, partnerships in research
and development, production, distribution and marketing are promising. An
excellent example of this partnership is the Indian biopharmaceutical industry.
Unfortunately, Pakistan is lacking behind in such partnerships.

Patent regimes and industrial innovations
Strong arguments are given both in favor and against the patents. Some patents
may be good for innovations while other may not. Patents on genes have
encouraged private funding in research and development activities, motivated
scientists to innovate, and research institutions such as universities to benefit from
their work. As a result the number of patents granted to universities and other public
institutions has increased worldwide. Similarly, the number of technology transfer
and commercialization offices in research institutions has increased as well.
However, many of the downstream patents such as those on genes are beginning
to work against innovations in developed countries. Patent holders either may not
allow other companies to work on it or keep demanding unreasonable royalties.
Pakistan needs a refined patent policy keeping a balance both for industry and
research centers or universities.
Public awareness and participation
Public trust in science, and particularly biotechnology, cannot be achieved without

open communication about the potential or perceived risks associated with the
technology. It may require dialogue with the public, policy makers and the scientific
community, and listening to, and taking account of, public concerns and
recommendations. To achieve maximum impact the public awareness and
participation programs must be planned, deliberate and sustained. This is likely to
be costly in the short term but justifiable in the long run.
The task of building greater scientific awareness will not be an easy one. It will
depend on the ability and willingness of many different groups of people, particularly
policy makers, the scientific community and the public themselves, to participate. To
improve information flows and engage in meaningful dialogue, the choice of the
most appropriate and cost effective mechanisms to promote public awareness and
to facilitate public participation in decision-making will be important.
Bridging the information gap
There seems to be a large technological information gap between the developed

and developing countries, among the scientists, policy makers, media and other
stakeholders within countries, and between regulators and industry. The ability of
any of these groups to articulate biotechnology issues may be limited to self

interest, and people with limited sources of information can be misleading as they
access resources with a similar viewpoint.
This information gap may be closed by building working groups of scientists,

regulators, industrialists and policy makers. Those with working knowledge of
biotechnology become advisers to those with limited experience in the field. Industry
will bring the commercial interests and scientists the technical experiences that
could help the government to make informed decisions. Such teams may be well
placed to conduct public awareness campaigns and encourage participation. Public
awareness and participation in Ghana is a good example to follow. See Annexure

Possible Development Models
Biotechnology is revolutionizing agricultural, medical, industrial and environmental

research and development. Some developing countries like Cuba, Korea and China
have taken strides to be considered frontrunners. Their size may not match that of
developed nations, but they have impressed and attracted the interest of companies
from developed countries. They serve as signals of the coming of age of the
biotechnology industry in developing countries. The cases of Brazil, Cuba, India,
Ghana and the Republic of Korea provide excellent examples of ingenious ways of
achieving and managing technical change within their national resources by building
local capacity and strategic alliances with leading nations. We can try to be like
them, but not necessarily copy, their strategies.
Use of technological niches
The use of technological niches to quickly develop facilities and human resource is
highlighted in the case of ONSA, Brazil, which created the virtual genomic institute.
A commercially viable example is the high demand for flowers and green
vegetables in developed countries has created a lucrative market for products from
developing countries. Even in time of starvation, this sector remains very strong.
Technologies such as biofertilizers and biopesticides targeting this market would
provide an added advantage. Extra jobs and wealth will be generated.
Currently, technology niches are not even on the agenda. While it is important to
focus on the most difficult problems, widely used products and services, and
socially or politically significant issues such as vaccine development, we do not
have any competitive edge in some of these areas. These niches provide an
opportunity from which biotechnology may grow and alliances may be developed to
later take on the more challenging and complex tasks.
Development of national biotechnology program
The national biotechnology program should clearly state the goals, when they
should be achieved and the levels of productivity expected. This program could
benefit from professionals at home and abroad. The Government could be
represented at a high level, preferably a minister or deputy minister, and interested
donors at a high level as well. The rest of the team could come from industry and

academic/research institutions with interests in the development of biotechnology.

This team could work with other experts to develop training programs to meet the
goals. It should also ensure that biotechnology is included in technical assistance
and other bilateral and multilateral agreements. Mechanisms for financing and
technology acquisition could be developed, marketed and/or negotiated.
National Commission on Biotechnology (NCB) has played a significant role in

developing biotech policy, framing bio-safety rules and guidelines in addition to
creating awareness about biotechnology by conducting series of meetings on
biotechnology related to agriculture, health, industry and environment to coordinate
between scientists and entrepreneurs to pave the way for commercialization of
biotechnology products so far developed by the research institutes in Pakistan. In
spite of achieving these milestones, important issues like Intellectual Proprietary
Rights, developing Biotech Parks and Commercialization of biotechnology products
remain to be tackled. These efforts focus on technology, talent, and capital, the key
ingredients needed to grow a bioscience-driven economy.
To facilitate and formulate policies for these issues, involvement and cooperation
between different ministries like Science & Technology, Environment, Agriculture
and ministry of Health is required on long term basis. There is need for a permanent
role of NCB as a focal organization to keep the pace of progress in the field of
biotechnology. To achieve these goals and coordinate between the said ministries,
it is proposed to establish a Department of Biotechnology under the ministry of
Science & Technology.
Establishing industries using incubators
Incubator facilities in research institutions and universities continue to be very

popular. They are important in commercializing research products, especially in
countries without mature venture capital markets. They are also important in
attracting finance as projects are likely to be funded if linked to incubator facilities
that have acquired a good reputation rather than in isolation. Incubator facilities may
have to be developed inside or within walking distance of research centers /
universities. Incubator facilities reduce the cost of space, research & development,
and professional advice. They also increase information flow, recombination of
ideas and expansion of knowledge horizon. They may also benefit from government
incentives, such as tax relief on equipment, rentals and salaries. For these reasons,
they could help increase the survival and generation of new firms. However, the
success of incubators has to be measured by the number of successful firms
graduated rather than the number of firms in tenancy.

Building interactive teams for industrial development
Although the idea of bringing industries, academia and Governments together is a

highly favored model, implementation remains loosely articulated. Interactive teams
formed around specific projects could include donors and government as financing
and technology transfer entities, industry as product developers and academia as
researchers and human resource developers. Therefore, identifying projects that
could allow the various public and private institutions to make some contribution and
realize benefits (social, economic or political) may be vital to the creation of
interactive teams. Once a start has been made, different players will identify other
areas of collaboration.
National agricultural research institutes and other biotechnology research centers

are owned and funded by government and work in isolation. Therefore, the flow of
new innovations to farmers is slow. To solve this problem, many research
institutions have taken on the role of extension services and marketing firms.
Unfortunately, their small size and limited financial and communication systems are
working against this one-in-all model. It would seem reasonable to integrate
extension services and agricultural marketing firms in order to increase
specialization and commercialization of products as well as receive feedback.
Establishing Life Sciences Parks
Globally industry clusters have played a significant role in the development of

various industries. The cluster model has been effectively driving growth and
innovation in the life science industry as well. Both multinational companies and
start-ups are setting up base in these geographical clusters. Almost all governments
across Asia Pacific region have allocated resources and framed policies to drive this
growth.
Singapores Biopolis, where some of the great research-work is on and the country
has given a leg up to its economy with this thrust to biomedical industry. India has
about 25 such parks and already boasts of the highest number of FDA-approved
plants. China is rapidly scaling up infrastructure and has build world class facilities.
Even the mature markets like Australia and Korea are banking heavily on life
in the country. This can be good food for thought for the policy makers in Pakistan.

Annexure - a
Institutes of Biotech & Genetic Engineering in
Pakistan
S/No Name of Institute Name of Head
Faisalabad
Ayub Agricultural Research Institute, Dr. Ghulam Ahmad
1.
Department of Biotechnology, Faisalabad. (Director General)
Center for Agricultural Biotechnology Dr. lftkhar Ahmad
2.
University of Agriculture, Faisalabad (Chairman)
Dr. Mohsin lqbal
Nuclear Institute for Agriculture and Bilogy (NIAB). P.O.Box
3. (Chief Scientist/Director
128, Jhang Road, Faisalabad
NIAB)
National Institute for Biotechnology & Genetic Engineering Dr. Ahmad Mukhtar Khalid
4. (NIBGE).
P. 0. Box - 577, Jhang Road, Faisalabad (Director General )
Rawalpindi / Islamabad
Agriculture Biotechnology Institute, Dr. Rasped Anwar
1.
National Agriculture Research Centre (NARC), Islamabad (Deputy Director General )
Biomedical & Genetic Engineering Division,
Dr. S. Qasim Mehdi
2. Dr. A. Q. Khan Research Laboratories, P.O. Box-2891,
(Director General)
Islamabad
Department of Biochemistry Dr. Azra Khanum
3.
University of Arid Agriculture, Rawalpindi (Chairperson)
Department of Plant Pathology Prof Dr. Irfan-ul-Haq
4.
University of Arid Agriculture, Rawalpindi (Chairman)
Department of Biological Sciences, Dr. Afsari Qureshi
5.
Quaid-i-Azam University, Islamabad (Chairperson)
Karachi
Dr. Punjwani Center for Molecular Medicine and Drug Dr. lqbal Chaudhary
1.
Research University of Karachi, Karachi (Acting Director)
Dr. Saifullah Khan
Plant Tissue Culture Lab, H.E.J Institute
2. (Assistant Professor &
Research Institute of Chemistry, Karachi
lncharge)
Dr. A. Q. Khan Institute of Biotechnology & Genetic Dr. Mujtaba Naqvi
3.
Engineering, Karachi (Director)
4. Department of Biotechnology, Dr. Altaf Khan

University of Karachi (Dean Faculty of Science)

Center for Molecular Genetics Dr. Nuzhat Ahmad
5.
University of Karachi, Karachi (Director Center)
Dept. of Microbiology Prof Dr. Shahana Urooj
6.
University of Karachi, Karachi Kazmi (Chairperson)
Lahore
Centre for Excellence in Molecular Biology, Dr. S. Riazuddin
1.
University of Punjab, Lahore (Director)
Institute of Biochemistry and Biotechnology, University of Prof. M. Waheed Akhter
2.
Punjab, Lahore (Dean Faculty of Science)
Biotechnology Laboratory Department of Botany Dr. lkram-ul-Haq
3.
Govt. College, University Lahore (Head)
School of Biological Sciences, Prof. M. Akhtar
4.
Punjab University, P.o.Box - 54590, Lahore (Director General)
Dept. of Microbiology and Molecular Genetics. Prof. Shahida Hasnain
5.
University of Punjab (Chairperson)
Biotechnology and Food Research Centre, Dr. Nazir Hussain Shah
6.
PCSIR Laboratories, Lahore (Director )
Peshawar
Institute of Biotechnology & Genetic Engineering, Dr. Zahoor Ahmad Swati
1.
N.W.F.P Agricultural University, Peshawar (Director)
Dr. Mohammad Subhan
Center for Animal Biotechnology Veterinary Research
2. Qureshi Officer-in-charge
Institute, N.W.F.P, Peshawar
CAB
Department of Biotechnology Dr. Farrukh Hussain
3.
University of Peshawar, Peshawar (Director)
Multan
Dr. Muhnmmad Islnm Gill
Central Cotton Research Institute,
1. (Chief Scientific Officer/
Old Shujabad Road, P.O.Box - 572, Multan
Director)
Quetta
Institute of Biochemistry, Dr. Masoom Yasin Zai
1.
University of Balochistan, Quetta (Professor )
Jamshoro
Institute of Biotechnology and Genetic Engineering, Dr. Umar Dahot
1.
University of Sindh, Jamshoro. (Director)

Annexure - b
Industries That Benefit
o The chemical industry: using biocatalysts to produce novel compounds, reduce waste
byproducts and improve chemical purity.
o The plastics industry: decreasing the use of petroleum for plastic production by
making green plastics from renewable crops such as corn or soybeans and, in the
future, cellulosic biomass.
o The paper industry: improving manufacturing processes, including the use of enzymes
to lower toxic byproducts from pulp processes.
o The textiles industry: lessening toxic byproducts of fabric dying and finishing
processes. Plus, fabric detergents are becoming more effective with the addition of
enzymes to their active ingredients.
o The food industry: improving baking processes, fermentation derived preservatives
and analysis techniques for food safety.
o The livestock industry: adding enzymes to increase nutrient uptake and decrease
phosphate byproducts.
o The energy industry: using enzymes to manufacture cleaner biofuels from agricultural
wastes.
Biological fuel cells
Fine and bulk chemicals
Chiral compound synthesis
Synthetic fibers for clothing
Pharmaceuticals
Food flavoring compounds
Biobased plastics
Biopolymers for automobile parts
Bioethanol for transportation
Nutritional oils
Oil and gas desulfurization
Leather degreasing
Biohydrogen
Biopolymers for plastic packaging
Coal bed methane water treatment
Chem/bio warfare agent decontamination
Pulp and paper bleaching
Biopulping (paper industry)
Specialty textile treatment
Enzyme food processing aids
Metal ore heap leaching
Electroplating/metal cleaning
Rayon and other synthetic fibers
Metal refining
Vitamin production
Sweetener production (high-fructose corn syrup)
Oil-well drill-hole completion (non-toxic cake breakers)
Road surface treatment for dust control
Textile dewatering
Vegetable oil degumming

Annexure - c
Some Consumer Goods Made With Industrial Biotech
Consumer Old Process New Industrial Biotech Enabling Consumer Benefit
Product Biotech Process Technology
Detergent Phosphates Addition of Genetically Elimination of
added as biotechnology enhanced microbes water pollution
brightening and enzymes as or fungi engineered from phosphates
cleaning agents brightening and to make enzymes Brighter, cleaner
cleaning agents: clothes with lower-
Proteases remove temperature wash
protein stains water
Lipases remove Energy savings
grease stains
Amylases remove
starch stains
Bread Potassium Addition of Microorganisms High-quality bread
bromate, a biotechnology genetically Longer shelf life
suspected enzymes to: enhanced to
cancer-causing produce baking
No potassium
enhance rising bromate
agent at certain enzymes (directed
strengthen dough
levels, added as evolution and
a preservative prolong freshness recombinant DNA)
and a dough
strengthening
agent
Polyester Polyester Biotech polyester Existing bacillus PLA polyester
Bedding produced (PLA) produced from microbe used to does not harbor
chemically from corn sugar feedstock ferment corn sugar body odor like
petroleum to lactic acid; lactic other fibers
feedstock acid converted to a Biodegradable
biodegradable
Not made from
polymer by heating;
petroleum
polymer made into
plastic products Does not give off
and polyester toxic smoke if
burned
Vitamin B2 Toxic One-step Genetically Biologically
chemicals, such fermentation process enhanced produced without
as aniline, used uses vegetable oil as microbe chemicals
in a nine-step a feedstock developed to Greatly reduces
chemical produce vitamin hazardous waste
synthesis B2 (directed generation and
process evolution) disposal
Stonewash Open-pit mining Fabric washed with Textile enzymes Less mining
ed Jeans of pumice; biotechnology produced by Softer fabric
fabric washed enzyme (cellulase) genetically

with crushed to fade and soften enhanced Reduces energy

pumice stone jeans or khakis Microbe consumption
and/or acid (extremophiles Lower cost
and recombinant
DNA)
Paper Wood chips Enzymes selectively Wood-bleaching Reduces use of
Bleaching boiled in a degrade lignin and enzymes chlorine bleach
harsh chemical break down wood produced by and reduces toxic
solution to yield cell walls during genetically dioxin in the
pulp for paper pulping enhanced environment
making microbes Cost savings due
(recombinant to lower energy
and chemical
DNA)
costs
Ethanol Food and feed Cellulase enzyme Genetically Renewable
Fuel grains fermented technology allows enhanced feedstock
into ethanol (a conversion of crop organism Reduces
technology that is residues (stems, developed to greenhouse gas
thousands of leaves, straw and produce enzymes emissions
years old) hulls) to sugars that that convert
Increases
are then converted to agricultural wastes
domestic energy
ethanol into fermentable
production
sugars (directed
evolution, gene Is more energy
shuffling) efficient to
produce than old
process
Antibiotics Chlorinated One-step biological Genetically 65% reduction in
solvents and process uses direct enhanced energy
hazardous fermentation to organism consumption
chemicals used produce antibiotic developed to Overall cost
to produce intermediate produce the key savings
antibiotics intermediate of
through chemical certain Antibiotics
synthesis (recombinant DNA)
Contact Surfactants Protease enzymes Genetically More effective
Lens and/or saline remove protein enhanced microbes contact lens
Solution solutions (do not deposits from the engineered to cleaning
remove protein contact lens make protease Less eye
deposits) used to enzymes (directed irritation
clean lenses evolution)

Annexure - d
Examples of Industrial Enzymes
Enzymes Source or Type Applications
Carbohydrases Laundry and dishwashing

detergents, industrial pipe/ tank
cleaners, textiles, pulp and paper,
fermentation ethanol
Alpha-amylase Bacterial -amylase (e.g., Textiles, starch syrups, laundry and

Bacillus subtilis), Fungal dishwashing detergents, paper
desizing, fermentation ethanol,
-amylase (e.g., Aspergillus
animal feed
niger), Alkaline
-amylase
-amylase From a strain of Bacillus Brewing, maltose syrup
Cellulase Dishwashing detergents, animal

feed, textiles, bioenergy production
Glucanase exo- -1,4-glucanase, endo- - Brewing industry

1,4-glucanase
Glucosidase Transforms isoflavone

phytoestrogens in soymilk
Dextranase Made by various microorganisms Hydrolyzes the polysaccharide

(e.g., Leuconostoc dextran
mesenteriodes)
Dextrinase Cleaves dextrin into two

molecules of glucose
Galactosidase Could increase yield of sucrose;

(melibiase) potential use in the beet sugar
industry
Glucoamylase Aspergillus niger, Rhizopus, Manufacture of dextrose syrup and

Endomyces high-fructose syrup
Hemmicellulase/Pentos Thermomyces lanuginosus, Baking, fruit juice manufacture,

anase/Xylanase Penicillium simplicissimum wood pulp processing

Invertase Manufacture of invert syrup from

cane or beet sugar (use is
minor)
Lactase Kluyveromyces lactis, Eliminates lactose from dairy

Asperigillus oryzae, Bacillus foods
Naringinase Debitter citrus peel
Pectinase Fruit processing
Pullulanase Klebsiella aerogenes, Bacillus Antistaling agent in baked goods

acidipullulyticus, Bacillus subtilis
Proteases Brewing, baking goods, protein

processing, distilled spirits, laundry
and dishwashing detergents, lens
cleaners, leather and fur,
chemicals
Acid proteinase Endothia parasitica, Rhizopus, Baking, improves dough

Aspergillus niger, A. oryzae handling
Alkaline protease Bacillus subtilis, Bacillus Detergents, leather and fur

licheniformis
Bromelain Pineapple stem Food industry
Pepsin Porcine or bovine stomach Cheese production
Peptidases
Aminopeptidase Lactococcus lactis Food and animal feed
Endo-peptidase
Subtilisin Bacillus subtilis var. Carlsberg, Chiral resolution of chemical

Bacillus lichenformis compounds or pharmaceuticals
Lipases and Esterases Phospholidases, pregastric Cleaners, leather and fur, dairy,
esterases, phosphatases chemicals
Aminoacylase Porcine kidney, Aspergillus Optical resolution of amino acids

melleus
Glutaminase Bacillus, Aspergillus Conversion of glutamine to

glutamate
Lysozyme Chicken egg white, Antibacterial (germicidal in dairy

Saccharomyces cerevisiae, industry)
Pichia pastoris
Penicillin acylase Bacillus megaterium, Chemical synthesis

Escherichia coli
Converts glucose syrup to high-
Somerase
fructose syrup in food industry
Chemicals, detergent bleaches,
Oxireductases
pulp bleaching
Saccharomyces cerevisiae, Chiral synthesis of chemicals
Alcohol
Thermoanarobium brockii
dehydrogenase
Amino acid oxidase Porcine kidney, snake venom Chiral resolution of racemic
amino acid mixtures
Aspergillus niger Desugaring of eggs
Catalase
Algae, bacteria, fungi, Steroid synthesis
Chloroperoxidase
mammalian tissues
Horseradish Laundry and wood pulp
Peroxidase
bleaches
Lyases
Brewing industry
Acetolactate
decarboxylase
Manufacture of L-alanine from
Aspartic -
L-aspartic
decarboxylase
Achromobacter liquidum Cosmetics
Histidase
Transferases
Manufacture of cyclodextrins
Cyclodextrin
from starch
glycosyltransferase
Sources:
Diversa and Novo Nordisk

Annexure - e
Agricultural biotech Products already in the Market
Canola
LibertyLink Canola (developed by Bayer CropScience) Introduced in 1995, LibertyLink
Canola allows growers a wide application window to apply Liberty herbicide over-the-top
during the growing season. Liberty herbicide controls over 100 grass and broadleaf weeds,
with no crop injury. This results in effective weed control while maintaining excellent crop
performance and yield.
InVigor Hybrid Canola (developed by Bayer CropScience) InVigor Hybrid Canola are
high-yielding hybrid canola varieties that are also tolerant to Liberty herbicide. InVigor
hybrid seed was first sold in Canada in 1996 and in the United States in 2000.
Roundup Ready Canola (developed by Monsanto) Roundup Ready Canola allows
growers to apply Roundup herbicide overthe- top of the crop during the growing season,
for weed control with enhanced crop safety.
Corn
NutriDense Corn (developed by BASF) This nutritionally enhanced corn contains a
stacked set of output traits designed to enhance animal feed performance. Traits include
higher concentrations of amino acids, oil and certain minerals.
Rogers brand Attribute Bt Sweet Corn (developed by Syngenta Seeds) Attribute
insect-protected sweet corn varieties from Syngenta provide a high level of built-in
protection against European corn borer and corn earworm, protecting crops from ear
damage and yield loss.
Agrisure GT Glyphosate-Tolerant Corn (developed by Syngenta) Developed from a
plant-derived glyphosate-resistant gene that is evenly expressed throughout the plant, corn
hybrids with Agrisure GT provide tolerance to in-crop applications of glyphosate-based
herbicides.
Agrisure CB/LL Agrisure (developed by Syngenta) features the Bt11 event, which has
been protecting cornfields since it was introduced in 1997. The Bt11 event utilizes the
naturally occurring soil bacterium Bacillus thuringiensis and produces a protein that is toxic
to lepidopteran insects. In addition, all hybrids with Agrisure CB/LL are tolerant to Liberty
herbicide. The LibertyLink benefit gives growers another option for weed control.
Agrisure RW (developed by Syngenta) features a modified fulllength Cry3Aa gene from
Bacillus thuringiensis, offers excellent builtin control of northern, western and Mexican corn
rootworms with outstanding yield results. An innovative trait conversion process allows
hybrids with Agrisure RW to reach their full yield potential while delivering outstanding
protection from corn rootworm.

Agrisure GT3000 (developed by Syngenta) is the stacked corn product that combines
Agrisure glyphosate-tolerant corn with corn borer and rootworm resistance to provide
growers with the experience of full advantage of all traits in a single elite genetic hybrid.
Herculex I Insect Protection (developed by Dow AgroSciences and Pioneer Hi-Bred
International, Inc.) These corn hybrids provide the broadest spectrum above-ground in-
plant insect protection currently available, including first- and secondgeneration European
corn borer, southwestern corn borer, black cutworm, western bean cutworm, fall armyworm,
sugarcane borer, southern corn stalk borer and lesser corn stalk borer. All Herculex I
hybrids also contain LibertyLink, making them tolerant to over-the-top applications of
Liberty herbicide, and some are available stacked with Roundup Ready Corn 2.
Herculex RW Rootworm Protection (co-developed by Dow AgroSciences and
Pioneer Hi-Bred International, Inc.) Corn hybrids containing Herculex RW rootworm
protection provide below ground in-plant corn rootworm protection against western,
northern and Mexican corn rootworm. All Herculex RW hybrids also contain LibertyLink,
making them tolerant to over-the-top applications of Liberty herbicide, and some are
available stacked with Roundup Ready Corn 2.
Herculex XTRA Insect Protection Corn (co-developed by Dow AgroSciences and
Pioneer Hi-Bred International, Inc.) Corn hybrids containing the Herculex XTRA insect
protection, a combined trait product of both Herculex I and Herculex RW, provide the
broadest spectrum above and below ground in-plant insect protection available on the corn
market. All Herculex XTRA hybrids also contain LibertyLink, making them tolerant to over-
the-top applications of Liberty herbicide, and some are available stacked with Roundup
Ready Corn 2.
LibertyLink Corn (developed by Bayer CropScience) Introduced in 1997 in the United
States and 1998 in Canada, LibertyLink Corn allows growers a wide application window to
apply Liberty herbicide over the top during the growing season. Liberty herbicide controls
over 100 grass and broadleaf weeds fast, without crop injury.
Roundup Ready Corn (developed by Monsanto) Approved in 1997, Roundup Ready
Corn allows over-the-top applications of Roundup herbicide during the growing season for
weed control.
YieldGard Corn Borer (developed by Monsanto) Introduced in 1997 in the United
States, YieldGard Corn Borer hybrids offer season-long, whole-plant protection from the
European corn borer and also controls the Southwestern corn borer.
YieldGard Rootworm-Protected Corn (developed by Monsanto) YieldGard corn
carries built-in protection against corn rootworm. Current products include YieldGard
Rootworm stacked with Roundup Ready technology.
YieldGard Plus Corn (developed by Monsanto) YieldGard Plus Corn is the first stack of
two insect-protection traits in a single seed, combining the built-in protection against
European corn borer and corn rootworm.

YieldGard Plus with Roundup Ready Corn (developed by Monsanto) YieldGard

Plus with Roundup Ready Corn is the first seed to contain three separate biotech traits, with
insect protection against European corn borer and corn rootworm and tolerance to over-the-
top applications of Roundup herbicide.
YieldGard VT Triple Corn (developed by Monsanto) hybrids are created using a
process called VecTran technology, which stands for Vector-Stack Transformation. The
vector combines two traits, Roundup Ready and YieldGard Rootworm, using a single
DNAinsertion process and is stacked with YieldGard Corn Borer.
Carnations
Moondust Carnation (introduced in 1996 by Florigene [formerly Calgene Pacific]) The
first mauve carnation, followed by Moonshadow (1998), a violet carnation. Conventional
breeding failed to produce these flowers with hues in the mauve-blue-violet range because
of a genetic gap; they lack the ability to produce the blue pigment, delphinidin. Florigene
also has an active research and development program to extend the vase life of flowers.
Cotton
Bollgard Insect-Protected Cotton (developed by Monsanto) Introduced in 1996, cotton
with Monsantos Bollgard gene protects against cotton bollworms, pink bollworms and
tobacco budworms. Bollgard cotton is a great example of how biotechnology can reduce
the amount of pesticide applications on a specific crop. According to the technology
provider, growers using Bollgard technology sprayed an average of 2.5 fewer applications
per acre than conventional cotton growers. This data is further underscored by EPA
research. In just one year, 1999, EPA estimated that growers who planted Bollgard cotton
reduced their insecticide application by 1.6 million pounds.
Bollgard II Insect-Protected Cotton (developed by Monsanto) Bollgard II is
Monsantos second generation of insect-protected cotton technology. This new cotton
technology is designed to offer new benefits to cotton growers, including a broader
spectrum of control of damaging insects and better defense against the development of
resistance in target insects. Research indicates that Bollgard II will provide greater control
of cotton bollworm, beet and fall armyworm, and soybean loopers compared with Bollgard.
LibertyLink Cotton (developed by Bayer CropScience) LibertyLink cotton allows
growers a wide application window to apply Liberty herbicide over the top during the
growing season. Liberty herbicide controls over 100 grass and broadleaf weeds, with no
crop injury. LibertyLink cotton is offered in top FiberMax varieties.
Roundup Ready Cotton (developed by Monsanto) Approved in 1996, Roundup
Ready cotton tolerates both over-the-top and postdirected applications of Roundup
herbicide. Roundup Ready cotton provides growers with an excellent resource for practicing
conservation tillage in their fields.
Roundup-Ready Flex Cotton (developed by Monsanto) Next Generation Roundup
Ready cotton is expected to provide growers with an expanded window of application of
Roundup herbicide.

WideStrike Insect Protection for Cotton (developed by Dow AgroSciences) is a two-

gene trait that provides a very wide spectrum of insect protection. This trait protects season
long against a broad range of damaging lepidopteran pests, including cotton bollworm, pink
bollworm, tobacco budworm, armyworms and loopers.
Milk and Dairy

Chymogen (developed by Genencor International and marketed by Chr. Hansens)
Chymogen is the biotechnologyproduced version of an enzyme (chymosin) found in calves
that makes milk curdle to produce cheese. Because it is produced through biotechnology, it
is purer and more plentiful; it also eliminates variability in the quality and availability of the
enzyme in calves stomachs. It is used in approximately 60 percent of all hard-cheese
products made today.
Posilac Bovine Somatotropin (BST) (developed by Monsanto) BST is a naturally
occurring protein hormone in cows that induces them to produce milk. BST improves milk
production by as much as 10 to 15 percent and is now used by farmers whose herds
represent over 30 percent of the nations cows. The FDA approved it in 1993.
ChyMax (fermentation-derived) (developed by Pfizer, marketed by Chr. Hansens)
ChyMax is another version of chymosin, an enzyme that causes milk to coagulate. It is an
advanced fermentation ingredient that is of higher purity, quality and activity than natural
rennet.
Papa ya
Rainbow and SunUp (developed by Cornell Research Foundation and the Papaya
Administrative Committee) Rainbow (a yellow-fleshed hybrid between a conventional
papaya and a genetically enhanced one) and SunUp (a red-fleshed transgenic papaya)
have been enhanced to resist papaya ringspot virus, the deadly disease that almost
eliminated the papaya industry in Hawaii during the 1990s.
Peanuts
Flavr Runner Naturally Stable Peanut (developed by Mycogen) these peanuts have a
modified fatty acid profile to produce nuts high in oleic acid. The benefit to the industry is
longer shelf life for nuts, candy and peanut butter.
Rapesed
Laurical (developed by Calgene, LLC) Laurical is a less expensive source of high-
quality raw materials for soaps, detergents and cocoa butter replacement fats. Rapeseed
plants with more than 45 percent laurate in oil have been produced.
Soybeans
Roundup Ready Soybeans (developed by Monsanto) Introduced in 1996, Roundup
Ready Soybeans allow growers to apply Roundup herbicide over-the-top during growing
season. The result is dependable weed control with no effect on crop performance or yield.

Miscelaneous
Messenger (developed by EDEN Bioscience) This is the first of a series of products
based on naturally occurring harpin protein technology. Approved by the EPA in April 2000,
Messenger stimulates growth and defense pathways inherent within each plant without
altering the plants DNA. Messenger treatments promote healthier plants and increased
yields, as well as increased disease resistance and deterrence of insects such as
nematodes. Messenger is a labeled product, currently being sold in cotton, citrus, apples,
strawberries, rice, tomatoes, peppers, cucurbit vegetables, cane berries, grass seed,
potatoes and many other crops.
In Development
ALFALFA
Roundup Ready Alfalfa (developed with Monsanto technology) allows over-the-top
applications of Roundup herbicide during the growing season for weed control.
Apples
Bt Insect-Protected Apple (developed with Monsanto technology) These apples will
contain built-in insect protection against the codling moth.
Bananas
Disease-Resistant Bananas (developed by DNA Plant Technology Corporation) These
bananas will be resistant to the fungal disease black sigatoka.
Canola
Disease-Resistant Canola (developed by DuPont) Canola that can resist yield-robbing
diseases such as Sclerotina.
Corn
Improved Drought Response Corn (developed by DuPont) Hybrid corn that can mine
the existing moisture in the soil more efficiently or survive drought periods and still produce
high yields.
EXTRAX Corn (developed by Monsanto), a new cornprocessing system developed by
Renessen, bolts on to the front of a conventional dry-grind ethanol plant, allowing the plant
to produce a greater array of high-value products. In addition to ethanol, a mill using the
EXTRAX corn processing system will produce food grade vegetable oil and improved
animal feed products.
Drought Tolerant Corn (developed by Monsanto) First-generation drought tolerant corn
is targeted to minimize uncertainty in farming by buffering against the effects of water
limitation, primarily in areas of annual water stress. In the U.S. this area has historically
been the dryland farms of the western Great Plains.

Drought Tolerant CornSecond Generation (developed by Monsanto) The second

generation of drought tolerant corn is aimed at boosting yield stability for broad-acre
applications and reducing water input required in water-limited environments.
Higher-yielding corn (developed by Monsanto) is aimed at boosting the intrinsic yield
potential of corn hybrids through insertion of key genes.
Mavera Corn (developed by Monsanto) The Mavera family of high-value corn products
have more than 50% more oil than conventional corn products. Mavera high-oil corn
products offer exceptional value when used in Renessens new EXTRAX processing
system. Mavera high-value corn is a family of products with increasing oil levels being
added over time from both advanced breeding and biotechnology approaches.
Nitrogen Utilization Corn (developed by Monsanto) Nitrogen utilization targets ways that
corn plants can use nitrogen more efficiently, exploring the potential to boost yield under
normal nitrogen conditions or to stabilize yield in low nitrogen environments.
SmartStax Corn (developed by Monsanto), a system that combines eight different
herbicide-tolerance and insect-protection genes, will include above- and below-ground
insect-protection systems, including Dow AgroSciences Herculex I and Herculex RW
technologies; Monsantos YieldGard VT Rootworm/RR2 and YieldGard VT PRO
technologies; and the two established weed control systems, Roundup Ready and
LibertyLink.
YieldGard Rootworm III (developed by Monsanto) is designed to offer increased
control and durability against the corn rootworm by using two distinct modes of action
providing two different approaches to insect control.
YieldGard VT PRO (developed by Monsanto) is the second generation of YieldGard
Corn Borer and broadens the spectrum of insect control to include corn earworm and fall
armyworm and increases the durability of the trait with the use of two proteins for dual
mode of actions for resistance.
Increased-Energy-Availability Corn (developed by DuPont) is corn that livestock can
more readily digest and more efficiently use nutrients in the grain.
Second-Generation YieldGard Corn Borer (developed by Monsanto) The second-
generation cornborer protected product in the YieldGard family is expected to provide an
even broader spectrum of insect control than todays YieldGard. In addition to the control of
the European and southwestern corn borer, field trials indicate it will provide enhanced
control of the corn earworm, fall armyworm and black cutworm. The next-generation corn
borer-protected corn will contain a new gene with a unique mode of action compared with
YieldGard Corn Borer or other products on the market, thus providing a defense against
insect resistance and ensuring that insect-protected products will remain effective and
continue to deliver benefits for many years to come.
Corn Amylase for Enhanced Ethanol Production (developed by Syngenta) Amylase
breaks starch down to sugar; including amylase expression in processor corn has the
potential to reduce the costs of ethanol production up to 10 percent.

Corn Broad Spectrum Lepidoptera Control (developed by Syngenta) will protect corn
above the ground by delivering high-level control of a broad spectrum of lepidopteran
insects including fall army worm, corn ear worm, western bean and black cutworm and
sugar cane borer, which are key pests in the United States, Brazil and Argentina. The gene
contained in the product has a distinct mode of action that is structurally and functionally
different from the genes contained in insect control technologies currently in the
marketplace
Corn Broad Spectrum Lepidoptera Control stacked with Corn Borer Control
(developed by Syngenta) A stack of two corn traits, Agrisure CB/LL product (Bt11) and
the Broad Spectrum Lepidoptera Control, which contains a novel insecticidal protein called
Vegetative Insecticidal Protein 3A. The combination of these traits targets in-crop control of
a broad range of lepidopteran pest larvae. This stack technology will unite two unique
genesthe first new approach to Lepidoptera control in corn since transgenic technology
was first introduced in 1995.
Drought tolerance (developed by Syngenta) This will bring together a combination of
leading genes to improve plants ability to perform under drought stress. These
combinations will deliver around 10 percent more yield in drought conditions, or allow
growers to maintain existing yields while using 50 percent less water.
Nitrogen Use Efficiency Trait (developed by DuPont) The Nitrogen Use Efficiency trait
will allow farmers to apply reduced quantities of nitrogen to their corn crop while maintaining
overall yields or alternatively increase yields at existing levels of nitrogen use.
Optimum GAT trait (developed by DuPont) The Optimum GAT (Glyphosate ALS
Tolerance) trait offers corn growers a new and better choice in herbicide tolerance that
maximizes yield and productivity, improves crop safety and expands weed control options.
DuPont plans to launch Optimum GAT in corn in 2010.
Dow AgroSciences Herbicide Tolerance Corn (DHT1) (developed by Dow
AgroSciences) will provide tolerance to broadleaf and grass herbicides including phenoxy
auxins and the fop family of herbicides. DHT1 will improve the performance of glyphosate
and glufosinate herbicides and further enhances the herbicide-tolerant cropping systems
and will be stacked with Herculex Insect Protection in-plant traits.
Coton
Bollgard III cotton (developed by Monsanto) thirdgeneration of insect control further
broadens the control spectrum of lepidopteran insects, by incorporating a new Bt protein.
The goal will be broad control of multiple pests with enhanced, season-long protection.
Cotton Lygus Control (developed by Monsanto) extends the spectrum of cotton insect
control to lygus bugs, piercing-sucking insects that damage bolls and reduce overall plant
health and yield.
Dicamba- and glufosinate-tolerant stacked with Roundup Ready Flex cotton
(developed by Monsanto) represents the industrys first three-way stack of herbicide-
tolerant technologies including Roundup Ready Flex, dicamba tolerance and glufosinate

tolerance. This product will provide two new, unique modes of action combined with
Roundup Ready Flex to provide cotton growers with the most effective weed management
system available.
Drought-tolerant cotton (developed by Monsanto) is designed to minimize risk in cotton
farming by providing yield stability in environments experiencing sporadic or consistent
water stress and by reducing water needs on irrigated acres.
GlyTol Cotton (developd by Bayer CropScience) GlyTol cotton is a weed-management
solution that will provide farmers a flexible and effective alternative system for weed
management in cotton. GlyTol cotton will offer tolerance to numerous formulations of
glyphosate herbicide.
GlyTol + LibertyLink Cotton (developd by Bayer Crop- Science) GlyTol +
LibertyLink cotton will have built-in stacked herbicide tolerance to both glyphosate and
glufosinate ammonium. This product will be an effective new weed management solution
that will provide additional options and flexibility to cotton growers.
Vegetative Insecticidal Protein Cotton (VipCot) (developed by Syngenta) This second-
generation insect control has a broader spectrum and a novel mode of action. VipCot will
provide growers an alternative to existing Bt products and will improve grower flexibility in
managing insect resistance.
Letuce
Roundup Ready Lettuce (developed with Monsanto technology) Allows over-the-top
applications of Roundup herbicide during the growing season for weed control.
Potatoes
Amflora Potatoes (developed by BASF) These potatoes with genetically enhanced
starches offer considerable benefits as raw materials in many industries. Paper, textile and
adhesives industries, for example, will soon be able to take advantage of BASFs Amflora
potato, which provides pure amylopectin starch directly from the potato tuber.
Rice
LibertyLink Rice (developed by Bayer CropScience) Bayer CropScience is obtaining
appropriate regulatory clearances in key countries. When LibertyLink Rice is used together
with Liberty herbicide, it will allow farmers greater weed control flexibility and may
promote water conservation.
Soybeans
Dicamba-tolerant Soybeans (developed by Monsanto) provide a new, unique mode of
action for weed control. It is designed to provide soybean growers with the most effective
and highest yielding weed-management system available when stacked with Monsantos
Roundup Ready 2 Yield trait.

First- and Second-Generation High-Oil Soybeans (developed by Monsanto) are

targeted to increased oil content in soybean to improve oil crushing yield, thus helping
processors meet the growing demand for vegetable oil for food and bio-fuel.
High-Stearate Soybeans (developed by Monsanto) are designed with elevated levels of
stearate to enhance the texture and reduce the levels of linolenic acid for increased stability
for many types of foods that require solid fat functionality.
First- and Second-Generation Higher-Yielding Soybeans (developed by Monsanto)
are aimed at boosting the intrinsic yield potential of the soybean through insertion of key
genes.
Improved-Protein Soybeans (developed by Monsanto) will provide soybeans with
improved taste, texture and health properties to help meet consumer demand for healthier
foods.
Insect-Protected + Roundup Ready 2 Yield Soybeans (developed by Monsanto) use
the same Bt technology widely adopted in corn and cotton to control lepidopteran insect
pests that are economically important for South American farmers. Insectprotected
soybeans are targeted to be introduced together with Roundup Ready 2 Yield soybeans
for effective control of both insects and weeds.
Omega-3 Enriched Soybeans (developed by Monsanto) represent a land-based source
of essential omega-3 fatty acids. This product is targeted to produce 20 percent stearidonic
acid omega-3 fatty acid with the taste, shelf life and oil stability of soybean oil.
Roundup Ready 2 Yield Soybeans (developed by Monsanto) are the second-
generation Roundup Ready soybean product designed to provide farmers with soybeans
that are tolerant to the Roundup family of agricultural herbicide and have enhanced yields,
with a target of 7 to 11 percent yield increase compared with Roundup Ready soybeans.
Soybean Disease Resistance (developed by Monsanto) is aimed at reducing the impact
of Asian Soybean Rust on soybean production.
Soybean Nematode Resistance (developed by Monsanto) is aimed at providing superior
control of Soybean Cyst Nematode compared with current genetic sources of resistance
that are available in commercial germplasm.
Vistive III Soybeans (developed by Monsanto) are designed by combining breeding
and biotechnology to lower linolenic and saturate content of soybean oil while boosting
oleic content to produce oil with the monounsaturated fat content of olive oil and the low
saturated fat content of canola oil.
LibertyLink Soybeans (developed by Bayer CropScience) When used together with
glufosinate ammonium herbicide (Liberty, Ignite 280), these soybeans will allow farmers
greater weed control flexibility and important weed resistance management strategies.
Soybeans with Improved Protein Functionality (developed by Dupont) is a food soy
ingredient that does a better job of improving quality and consistency of food products.

Optimum GAT trait (developed by DuPont) The Optimum GAT (Glyphosate ALS
Tolerance) trait offers soybean growers a new and better choice in herbicide tolerance that
maximizes yield and productivity, improves crop safety and expands weed control options.
DuPont plans an initial introduction in 2009.
High Oleic Soybeans (developed by DuPont and Bunge) High oleic soybeans will be the
first transgenic product that provides direct consumer benefits. They are a low trans fat, low
saturate product with high heat stability for improved frying performance. The oils high heat
stability in industrial and transportation settings also enables the development of renewable,
environmentally friendly options to petroleum-based products. The high oleic soybean oil
trait is on track for commercial introduction in 2009.
Dow AgroSciences Herbicide Tolerance Soybeans (DHT2) (developed by Dow
AgroSciences) will provide tolerance to broadleaf and grass herbicides, including phenoxy
auxins, and the fop family of herbicides. DHT2 will improve the performance of glyphosate
herbicides and further enhances the herbicide tolerant cropping system.
Strawberries
Strawberry (developed by DNA Plant Technology Corporation) The company is adding
genes to confer resistance to glyphosate herbicide and fungal diseases.
Sugar Beets
Roundup Ready Sugar Beets (developed by Monsanto) Roundup Ready sugar
beets are tolerant of Roundup herbicide and provide growers with a new weed-control
option.
Turf Gras
Roundup Ready Creeping Bentgrass (developed with Monsanto technology) allows
over-the-top applications of Roundup herbicide to control Poa Annua, Poa Trivialis and
other weeds of turf on golf course fairways and greens allowing more flexible weed control
and reduced turf-management inputs.
eNERGY CROPS
Blade Switchgrass (developed by Ceres) Coming in the spring of 2009, these are the
first switchgrass cultivars developed specifically for biofuels.
Blade Sorghum (developed by Ceres) Coming in the spring of 2009, this is a high-
biomass sorghum developed specifically for biofuels.
Miscelaneous
AquaAdvantage Salmon, Tilapia, Trout and Flounder (developed by Aqua Bounty
Farms) The AquaAdvantage salmon have the capability of growing from egg to market
size (6 to 10 lb.) in one to one-and-a-half years. Conventional fish-breeding techniques
require two to three years to bring a fish to market. This new salmon could make fish
farming more environmentally sustainable, decrease over-fishing of wild salmon and lower

consumer costs. Aqua Bounty expects to introduce the AquaAdvantage salmon within
two to three years to a public for whom salmon is an increasingly popular food.
Genetically Modified Fruits and Vegetables with Longer Postharvest Shelf Life
(developed by Agritope, Inc., a wholly owned subsidiary of Epitope, Inc.) Using
ethylene-control technology, Agritope, Inc., has created delayed-ripening, longerlasting
tomatoes and raspberries.
Phytase for Animal Feed (developed by Syngenta and Zymetrics) The phytase enzyme
releases phosphorous-based nutrients in animal feed in a form that can be easily digested
by single-stomach animals such as pigs, chickens and turkeys. A phytase supplement can
enhance the nutritional value of the feed and reduce phosphorus levels in animal manure,
which can help improve environmental quality. The new microbial (Zymetrics) and corn
phytase (Syngenta) supplements are designed with enhanced thermostability, which
provides livestock producers more options in developing feed rations.

Annexure - f
Time Line in Biotechnology
8000 B.C.
Humans domesticate crops and livestock.
Potatoes first cultivated for food.
4000-2000 B.C.
Biotechnology first used to leaven bread and ferment beer, using yeast
(Egypt).
Production of cheese and fermentation of wine (Sumeria, China and Egypt).
Babylonians control date palm breeding by selectively pollinating female
trees with pollen from certain male trees.
500 B.C.
First antibiotic: moldy soybean curds used to treat boils (China).
A.D. 100
First insecticide: powdered chrysanthemums (China).
1322
An Arab chieftain first uses artificial insemination to produce superior horses.
1590
Janssen invents the microscope.
1663
Hooke discovers existence of the cell.
1675
Leeuwenhoek discovers bacteria.
1761
Koelreuter reports successful crossbreeding of crop plants in different
species.
1797
Jenner inoculates a child with a viral vaccine to protect him from smallpox.
1830-1833
1830-Proteins discovered.
1833-First enzyme discovered and isolated.
1835-1855
Schleiden and Schwann propose that all organisms are composed of cells,
and Virchow declares, "Every cell arises from a cell."
1857
Pasteur proposes microbes cause fermentation.
1859
Charles Darwin publishes the theory of evolution by natural selection. The
concept of carefully selecting parents and culling the variable progeny greatly

influences plant and animal breeders in the late 1800s despite their
ignorance of genetics.
1865
Science of genetics begins: Austrian monk Gregor Mendel studies garden
peas and discovers that genetic traits are passed from parents to offspring in
a predictable way-the laws of heredity.
1870-1890
Using Darwin's theory, plant breeders crossbreed cotton, developing
hundreds of varieties with superior qualities.
Farmers first inoculate fields with nitrogen-fixing bacteria to improve yields.
William James Beal produces first experimental corn hybrid in the laboratory.
1877-A technique for staining and identifying bacteria is developed by Koch.
1878-The first centrifuge is developed by Laval.
1879-Fleming discovers chromatin, the rod-like structures inside the cell
nucleus that later came to be called chromosomes.
1900
Drosophila (fruit flies) used in early studies of genes.
1902
The term immunology first appears.
1906
The term genetics is introduced.
1911
The first cancer-causing virus is discovered by Rous.
1914
Bacteria are used to treat sewage for the first time in Manchester, England.
1915
Phages, or bacterial viruses, are discovered.
1919
First use of the word biotechnology in print.
1920
The human growth hormone is discovered by Evans and Long.
1928
Penicillin discovered as an antibiotic: Alexander Fleming.
A small-scale test of formulated Bacillus thuringiensis (Bt) for corn borer
control begins in Europe. Commercial production of this biopesticide begins
in France in 1938.
Karpechenko crosses radishes and cabbages, creating fertile offspring
between plants in different genera.
Laibach first uses embryo rescue to obtain hybrids from wide crosses in crop
plants-known today as hybridization.
1930

U.S. Congress passes the Plant Patent Act, enabling the products of plant
breeding to be patented.
1933
Hybrid corn, developed by Henry Wallace in the 1920s, is commercialized.
Growing hybrid corn eliminates the option of saving seeds. The remarkable
yields outweigh the increased costs of annual seed purchases, and by 1945,
hybrid corn accounts for 78 percent of U.S.-grown corn.
1938
The term molecular biology is coined.
1941
The term genetic engineering is first used, by Danish microbiologist A. Jost in
a lecture on reproduction in yeast at the technical institute in Lwow, Poland.
1942
The electron microscope is used to identify and characterize a
bacteriophage-a virus that infects bacteria.
Penicillin mass-produced in microbes.
1944
DNA is proven to carry genetic information-Avery et al.
Waksman isolates streptomycin, an effective antibiotic for tuberculosis.
1946
Discovery that genetic material from different viruses can be combined to
form a new type of virus, an example of genetic recombination.
Recognizing the threat posed by loss of genetic diversity, the U.S. Congress
provides funds for systematic and extensive plant collection, preservation
and introduction.
1947
McClintock discovers transposable elements, or "jumping genes," in corn.
1949
Pauling shows that sickle cell anemia is a "molecular disease" resulting from
a mutation in the protein molecule hemoglobin.
1951
Artificial insemination of livestock using frozen semen is accomplished.
1953
The scientific journal Nature publishes James Watson and Francis Crick's
manuscript describing the double helical structure of DNA, which marks the
beginning of the modern era of genetics.
1955
An enzyme involved in the synthesis of a nucleic acid is isolated for the first
time.
1956

Kornberg discovers the enzyme DNA polymerase I, leading to an

understanding of how DNA is replicated.
1958
Sickle cell anemia is shown to occur due to a change of a single amino acid.
DNA is made in a test tube for the first time.
1959
Systemic fungicides are developed. The steps in protein biosynthesis are
delineated.
IN THE 1950s
Discovery of interferons.
First synthetic antibiotic.
1960
Exploiting base pairing, hybrid DNA-RNA molecules are created.
Messenger RNA is discovered.
1961
USDA registers first biopesticide: Bacillus thuringiensis, or Bt.
1963
New wheat varieties developed by Norman Borlaug increase yields by 70
percent.
1964
The International Rice Research Institute in the Philippines starts the Green
Revolution with new strains of rice that double the yield of previous strains if
given sufficient fertilizer.
1965
Harris and Watkins successfully fuse mouse and human cells.
1966
The genetic code is cracked, demonstrating that a sequence of three
nucleotide bases (a codon) determines each of 20 amino acids. (Two more
amino acids have since been discovered.)
1967
The first automatic protein sequencer is perfected.
1969
An enzyme is synthesized in vitro for the first time.
1970
Norman Borlaug receives the Nobel Peace Prize (see 1963).
Discovery of restriction enzymes that cut and splice genetic material, opening
the way for gene cloning.
1971
First complete synthesis of a gene.
1972

The DNA composition of humans is discovered to be 99 percent similar to

that of chimpanzees and gorillas.
Initial work with embryo transfer.
1973
Stanley Cohen and Herbert Boyer perfect techniques to cut and paste DNA
(using restriction enzymes and ligases) and reproduce the new DNA in
bacteria.
1974
The National Institutes of Health forms a Recombinant DNA Advisory
Committee to oversee recombinant genetic research.
1975
Government first urged to develop guidelines for regulating experiments in
recombinant DNA: Asilomar Conference, California.
The first monoclonal antibodies are produced.
1976
The tools of recombinant DNA are first applied to a human inherited disorder.
Molecular hybridization is used for the prenatal diagnosis of alpha
thalassemia.
Yeast genes are expressed in E. coli bacteria.
The sequence of DNA base pairs for a specific gene is determined.
First guidelines for recombinant DNA experiments released: National
Institutes of Health-Recombinant DNA Advisory Committee.
1977
First expression of human gene in bacteria.
Procedures developed for rapidly sequencing long sections of DNA using
electrophoresis.
1978
High-level structure of virus first identified.
Recombinant human insulin first produced.
North Carolina scientists show it is possible to introduce specific mutations at
specific sites in a DNA molecule.
1979
Human growth hormone first synthesized.
IN THE 1970s
First commercial company founded to develop genetically engineered
products.
Discovery of polymerases.
Techniques for rapid sequencing of nucleotides perfected.
Gene targeting.
RNA splicing.
1980

The U.S. Supreme Court, in the landmark case Diamond v. Chakrabarty,

approves the principle of patenting organisms, which allows the Exxon oil
company to patent an oil-eating microorganism.
The U.S. patent for gene cloning is awarded to Cohen and Boyer.
The first gene-synthesizing machines are developed.
Researchers successfully introduce a human gene-one that codes for the
protein interferon-into a bacterium.
Nobel Prize in Chemistry awarded for creation of the first recombinant
molecule: Berg, Gilbert, Sanger.
1981
Scientists at Ohio University produce the first transgenic animals by
transferring genes from other animals into mice.
Chinese scientist becomes the first to clone a fish-a golden carp.
1982
Applied Biosystems, Inc., introduces the first commercial gas phase protein
sequencer, dramatically reducing the amount of protein sample needed for
sequencing.
First recombinant DNA vaccine for livestock developed.
First biotech drug approved by FDA: human insulin produced in genetically
modified bacteria.
First genetic transformation of a plant cell: petunia.
1983
The polymerase chain reaction (PCR) technique is conceived. PCR, which
uses heat and enzymes to make unlimited copies of genes and gene
fragments, later becomes a major tool in biotech research and product
development worldwide.
The first genetic transformation of plant cells by TI plasmids is performed.
The first artificial chromosome is synthesized.
The first genetic markers for specific inherited diseases are found.
First whole plant grown from biotechnology: petunia.
First proof that modified plants pass their new traits to offspring: petunia.
1984
The DNA fingerprinting technique is developed.
The entire genome of the human immunodeficiency virus is cloned and
sequenced.
1985
Genetic markers found for kidney disease and cystic fibrosis.
Genetic fingerprinting entered as evidence in a courtroom.
Transgenic plants resistant to insects, viruses and bacteria are field-tested
for the first time.

The NIH approves guidelines for performing gene-therapy experiments in

humans.
1986
First recombinant vaccine for humans: hepatitis B.
First anticancer drug produced through biotech: interferon.
The U.S. government publishes the Coordinated Framework for Regulation
of Biotechnology, establishing more stringent regulations for rDNA organisms
than for those produced with traditional genetic modification techniques.
A University of California-Berkeley chemist describes how to combine
antibodies and enzymes (abzymes) to create pharmaceuticals.
The first field tests of transgenic plants (tobacco) are conducted.
The Environmental Protection Agency approves the release of the first
transgenic crop-gene-altered tobacco plants.
The Organization of Economic Cooperation and Development (OECD) Group
of National Experts on Safety in Biotechnology states: "Genetic changes
from rDNA techniques will often have inherently greater predictability
compared to traditional techniques" and "risks associated with rDNA
organisms may be assessed in generally the same way as those associated
with non-rDNA organisms."
1987
First approval for field test of modified food plants: virus-resistant tomatoes.
Frostban, a genetically altered bacterium that inhibits frost formation on crop
plants, is field-tested on strawberry and potato plants in California, the first
authorized outdoor tests of a recombinant bacterium.
1988
Harvard molecular geneticists are awarded the first U.S. patent for a
genetically altered animal-a transgenic mouse.
A patent for a process to make bleach-resistant protease enzymes to use in
detergents is awarded.
Congress funds the Human Genome Project, a massive effort to map and
sequence the human genetic code as well as the genomes of other species.
1989
First approval for field test of modified cotton: insect-protected (Bt) cotton.
Plant Genome Project begins.
IN THE 1980s
Studies of DNA used to determine evolutionary history.
Recombinant DNA animal vaccine approved for use in Europe.
Use of microbes in oil spill cleanup: bioremediation technology.
Ribozymes and retinoblastomas identified.
1990

Chy-MaxTM, an artificially produced form of the chymosin enzyme for cheese-

making, is introduced. It is the first product of recombinant DNA technology in
the U.S. food supply.
The Human Genome Project-an international effort to map all the genes in
the human body-is launched.
The first experimental gene therapy treatment is performed successfully on a
4-year-old girl suffering from an immune disorder.
The first transgenic dairy cow-used to produce human milk proteins for infant
formula-is created.
First insect-protected corn: Bt corn.
First food product of biotechnology approved in U.K.: modified yeast.
First field test of a genetically modified vertebrate: trout.
1992
American and British scientists unveil a technique for testing embryos in vitro
for genetic abnormalities such as cystic fibrosis and hemophilia.
The FDA declares that transgenic foods are "not inherently dangerous" and
do not require special regulation.
1993
Merging two smaller trade associations creates the Biotechnology Industry
Organization (BIO).
FDA approves bovine somatotropin (BST) for increased milk production in
dairy cows.
1994
First FDA approval for a whole food produced through biotechnology:
FLAVRSAVRTM tomato.
The first breast cancer gene is discovered.
Approval of recombinant version of human DNase, which breaks down
protein accumulation in the lungs of CF patients.
BST commercialized as POSILAC bovine somatotropin.
1995
The first baboon-to-human bone marrow transplant is performed on an AIDS
patient.
The first full gene sequence of a living organism other than a virus is
completed, for the bacterium Hemophilus influenzae.
Gene therapy, immune system modulation and recombinantly produced
antibodies enter the clinic in the war against cancer.
1996
The discovery of a gene associated with Parkinson's disease provides an
important new avenue of research into the cause and potential treatment of
the debilitating neurological ailment.
1997
First animal cloned from an adult cell: a sheep named Dolly in Scotland.
First weed- and insect-resistant biotech crops commercialized: Roundup

Ready soybeans and Bollgard insect-protected cotton.
Biotech crops grown commercially on nearly 5 million acres worldwide:
Argentina, Australia, Canada, China, Mexico and the United States.
A group of Oregon researchers claims to have cloned two Rhesus monkeys.
1998
University of Hawaii scientists clone three generations of mice from nuclei of
adult ovarian cumulus cells.
Human embryonic stem cell lines are established.
Scientists at Japan's Kinki University clone eight identical calves using cells
taken from a single adult cow.
The first complete animal genome, for the C. elegans worm, is sequenced.
A rough draft of the human genome map is produced, showing the locations
of thousands of genes.
Five Southeast Asian countries form a consortium to develop disease-
resistant papayas.
IN THE 1990s
First conviction using genetic fingerprinting in the U.K.
Discovery that hereditary colon cancer is caused by defective DNA repair
gene.
Recombinant rabies vaccine tested in raccoons.
Biotechnology-based biopesticide approved for sale in the United States.
Patents issued for mice with specific transplanted genes.
First European patent on a transgenic animal issued for transgenic mouse
sensitive to carcinogens.
2000
First complete map of a plant genome developed: Arabidopsis thaliana.
Biotech crops grown on 108.9 million acres in 13 countries.
"Golden rice" announcement allows the technology to be available to
developing countries in hopes of improving the health of undernourished
people and preventing some forms of blindness.
First biotech crop field-tested in Kenya: virus-resistant sweet potato.
Rough draft of the human genome sequence is announced.
2001
First complete map of the genome of a food plant completed: rice.
Researchers with China's National Hybrid Rice Research Center report
developing a "super rice" that could produce double the yield of normal rice.
Complete DNA sequencing of the agriculturally important bacteria
Sinorhizobium meliloti, a nitrogen-fixing species, and Agrobacterium
tumefaciens, a plant pest.

A single gene from Arabidopsis inserted into tomato plants to create the first
crop able to grow in salty water and soil.
2002
The first draft of a functional map of the yeast proteome, an entire network of
protein complexes and their interactions, is completed. A map of the yeast
genome was published in 1996.
International consortia sequence the genomes of the parasite that causes
malaria and the species of mosquito that transmits the parasite.
The draft version of the complete map of the human genome is published,
and the first part of the Human Genome Project comes to an end ahead of
schedule and under budget.
Scientists make great progress in elucidating the factors that control the
differentiation of stem cells, identifying over 200 genes that are involved in
the process.
Biotech crops grown on 145 million acres in 16 countries, a 12 percent
increase in acreage. More than one-quarter (27 percent) of the global
acreage was grown in nine developing countries.
Researchers announce successful results for a vaccine against cervical
cancer, the first demonstration of a preventative vaccine for a type of cancer.
Scientists complete the draft sequence of the most important pathogen of
rice, a fungus that destroys enough rice to feed 60 million people annually.
By combining an understanding of the genomes of the fungus and rice,
scientists can elucidate the molecular basis of the interactions between the
plant and pathogen.
Scientists are forced to rethink their view of RNA when they discover how
important small pieces of RNA are in controlling many cell functions.
Japanese pufferfish genome is sequenced. The pufferfish sequence is the
smallest known genome of any vertebrate.
Scientists at Stony Brook University in New York assemble a synthetic virus,
polio, using genome sequence information. The project raises ethical and
security questions.
2003
Researchers find a vulnerability gene for depression and make strides in
detecting genetic links to schizophrenia and bipolar disorder.
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 fluorescence gene.
Worldwide biotech crop acreage rises 15 percent to hit 167.2 million acres in
18 countries. Brazil and the Philippines grow biotech crops for the first time in
2003. Also, Indonesia allows consumption of imported biotech foods, and
China and Uganda accept biotech crop imports.
The U.K. approves its first commercial biotech crop in eight years. The crop
is a biotech herbicide-resistant corn used for cattle feed.

The U.S. Environmental Protection Agency approves the first transgenic

rootworm-resistant corn, which may save farmers $1 billion annually in crop
losses and pesticide use.
An endangered species (the banteng) is cloned for the first time. 2003 also
brought several other cloning firsts, including mules, horses and deer.
Dolly, the cloned sheep that made headlines in 1997, is euthanized after
developing progressive lung disease. Dolly was the first successful clone of
an adult mammal.
Japanese researchers develop a biotech coffee bean that is naturally
decaffeinated.
China's State Food and Drug Administration grants the world's first regulatory
approval of a gene therapy product, Gendicine, developed by Shenzhen
SiBiono GenTech. The product delivers the p53 gene as a therapy for
squamous cell head and neck cancer.
2004
The FDA approves the first anti-angiogenic drug for cancer, AVASTIN
(bevacizumab).
The FDA clears a DNA microarray test system, the AmpliChip Cytochrome
P450 Genotyping Test, to aid in selecting medications for a wide variety of
common conditions.
An RNA-interference product for age-related "wet" macular degeneration
becomes the first RNAi product to enter a clinical trial.
The United Nations Food and Agriculture Organization endorses biotech
crops and states that biotechnology is a complementary tool to traditional
farming methods that can help poor farmers and consumers in developing
nations.
The National Academy of Sciences' Institute of Medicine finds biotech crops
do not pose any more health risks than do crops created by other
techniques, and that food safety evaluations should be based on the
resulting food product, not the technique used to create it.
FDA finds biotech wheat safe after a food safety review.
Monsanto introduces low-linolenic soybeans (produced through conventional
breeding methods) that will reduce or eliminate trans fatty acids in processed
soybean oil.
Chicken genome sequenced by the Chicken Genome Sequencing
Consortium.
First cloned pet, a kitten, is delivered to its owner.
Laboratory rat genome is sequenced.
Researchers complete the sequence of the chimpanzee-humanity's closest
primate relative.
The Canadian biotech company Iogen achieves the first commercial
production and delivery of bioethanol, producing the fuel with biotech
enzymes and wheat straw.

California voters pass Proposition 71, which supports embryonic stem cell
research with $3 billion in funding over 10 years.
2005
Researchers at the University of Georgia successfully produce a cow cloned
from the cells of a carcass.
FDA for the first time approves a drug for a specific race. The drug,
NitroMed's BiDil, treats congestive heart failure in self-identified black
patients. The company hopes a genetic test can be developed to identify
patients likely to benefit, regardless of race.
The Energy Policy Act is passed and signed into law, authorizing numerous
incentives for bioethanol development.
The National Institutes of Health in December launches a pilot project to
determine the feasibility of The Cancer Genome Atlas. The ultimate goal
would be a complete map of the genomic changes involved in all types of
human cancer.
Using new genome sequence information, scientists at the Centers for
Disease Control & Prevention partially synthesize the flu virus that killed at
least 20 million people worldwide in 1918-1919.
Scientists at Harvard University report success in converting skin cells into
embryonic stem cells through fusion with existing embryonic stem cells.
USDA, Monsanto and Genaissance Pharmaceuticals announce a joint
soybean genome project.
The British government approves the Equine Fertility Unit's research in using
nuclear transfer in horse cloning.
On May 7, the one billionth acre of biotech seed is planted.
The World Health Organization (WHO) issues the report Modern Food
Biotechnology, Human Health and Development, which states biotech foods
can contribute to enhancing human health and development. According to
the report, biotech foods can increase crop yield, food quality, and the
diversity of foods which can be grown in a given area. They lead to better
health and nutrition and thereby help raise health and living standards.
The British research firm PG Economics Ltd. finds that the global use of
biotech crops has added $27 billion to farm income, and greatly reduced
agriculture's negative impacts on the environment.
The National Science Foundation, USDA, and the Department of Energy
award $32 million to a team of university and private laboratory researchers
to sequence the corn genome.
A consortium of scientists led by the National Human Genome Research
Institute publishes the dog genome, which belongs to a 12-year-old boxer.
Global biotech crop acreage reaches 222 million acres.
2006

A team of researchers headed by the University of Illinois receives a $10

million federal grant to complete the sequence of the swine genome. The
project is expected to be completed within two years.
In his State of the Union address, President Bush expresses support for
bioethanol made from agricultural wastes. "Doesn't it make sense," he asked,
"to determine whether or not we can use these raw materials to make
something out of nothing so that we continue the advance of ethanol and so
the market for ethanol expands throughout the United States?"
The National Institutes of Health begins a 10-year, 10,000-patient study
using a genetic test that predicts breast-cancer recurrence and guides
treatment. Patients whose cancer is deemed unlikely to recur will be spared
chemotherapy. The genetic test, Oncotype DXTM was developed by the
biotech company Genomic Health and is already commercially available.
In January, the American Dietetic Association (ADA) publishes a reaffirmed
statement of support on agricultural and food biotechnology. The ADA states
that agricultural biotechnology techniques can enhance the quality, safety,
nutritional value, and variety of food available for human consumption while
increasing the efficiency of food production, food processing, food
distribution, and environmental and waste management.
Dow AgroSciences announces it has received the first regulatory approval for
a plant-made vaccine from USDA's Center for Veterinary Biologics. The
vaccine protects poultry from Newcastle disease, and is the first plant-made
vaccine to be approved.
Renessen LLC, a joint venture of Monsanto and Cargill, receives approval
from USDA to begin selling the first crop improved through biotechnology
with added benefits for use in animal feed. The product, Mavera High
Value Corn with Lysine, has been improved to grow with increased levels of
lysine, an amino acid that is essential for animal diets, especially those of
swine and poultry.
USDA awards $5 million to a consortium of public wheat breeders and 18
universities for wheat genome research.
Researchers develop biotech pigs that produce high levels of omega-3 fatty
acids. The biotech pigs were developed by inserting the "fat-1" gene that
comes from the roundworm Caenorhabditis elegans. The biotech pigs were
cloned, and six of the 10 clones produced increased levels of omega-3 fatty
acids, which are believed to ward off heart disease.
The World Trade Organization issues a confidential final ruling on the
U.S./Canada/Argentine challenge against the European Union (EU) on
approval of new biotech crops. According to news reports, the ruling
concludes that the EU breached its trade commitments with respect to 21
agricultural biotechnology products-including types of oilseed, rape, maize
and cotton.
The French agriculture ministry authorizes 17 new field tests for biotech corn
and tobacco crops.

Source:
Access Excellence
Biotech 90: Into the Next Decade, G. Steven Burrill with the Ernst & Young High Technology Group
Biotechnology Industry Organization
Genentech, Inc.
Genetic Engineering News
International Food Information Council
ISB News Report
International Service for the Acquisition of Agri-Biotech Applications
Texas Society for Biomedical Research
Science
Science News
The Scientis

Annexure - g
Glossary
A
ADME An acronym for absorption, distribution, metabolism and excretion; refers to how a
drug travels through the body.
Acclimatization Adaptation of an organism to a new environment.
Action letter An official FDA communication that informs a company seeking a drug
approval of a decision by the agency. An approval letter allows commercial marketing of the
product.
Active immunity A type of acquired immunity whereby resistance to a disease is built up
by either having the disease or receiving a vaccine to it.
Adjuvant Insoluble material that increases the formation and persistence of antibodies
when injected with an antigen.
Aerobic Needing oxygen for growth.
Agrobacterium tumefaciens A common soil bacterium used as a vector to create
transgenic plants.
Allele Any of several alternative forms of a gene.
Allogenic Of the same species, but with a different genotype. Also allogeneic.
Alzheimers disease A disease characterized by, among other things, progressive loss of
memory. The development of Alzheimers disease is thought to be associated, in part,
with possessing certain alleles of the gene that encodes apolipoprotein E.
Amino acids Building blocks of proteins. There are 20 common amino acids: alanine,
arginine, aspargine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine,
isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan,
tyrosine and valine.
Two more amino acids have been discovered in microbes: selenocysteine and pyrrolysine.
Amplification The process of increasing the number of copies of a particular gene or
chromosomal sequence.
Anaerobic Growing in the absence of oxygen.
Antibiotic Chemical substance formed as a metabolic byproduct in bacteria or fungi and
used to treat bacterial infections. Antibiotics can be produced naturally, using
microorganisms, or synthetically.
Antibody Protein produced by humans and higher animals in response to the presence of
a specific antigen.

Anticodon Triplet of nucleotide bases (codon) in transfer RNA that pairs with (is
complementary to) a triplet in messenger RNA. For example, if the codon is UCG, the
anticodon is AGC. See Base; Base pair; Complementarity.
Antigen A substance that, when introduced into the body, induces an immune response by
a specific antibody.
Antigenic determinant See Hapten.
Antihemophilic factors A family of whole-blood proteins that initiate blood clotting. Some
of these proteins, such as factor VIII, can be used to treat hemophilia. See Factor VIII;
Kidney plasminogen activator.
Antisense A piece of DNA producing a mirror image (antisense) messenger RNA that is
opposite in sequence to one directing protein synthesis. Antisense technology is used to
selectively turn off production of certain proteins.
Antiserum Blood serum containing specific antibodies against an antigen. Antisera are
used to confer passive immunity to many diseases.
Apolipoprotein E (Apo E) Certain alleles of the gene that encodes the protein
apolipoprotein E have been associated with the development of heart disease and
Alzheimers disease.
Assay Technique for measuring a biological response.
Attenuated Weakened; with reference to vaccines, made from pathogenic organisms that
have been treated so as to render them avirulent.
Autoimmune disease A disease in which the body produces antibodies against its own
tissues.
Autoimmunity A condition in which the body mounts an immune response against one of
its own organs or tissues.
Autosome Any chromosome other than a sex chromosome.
Avirulent Unable to cause disease.
B
Bacillus subtilis A bacterium commonly used as a host in recombinant DNA experiments.
Important because of its ability to secrete proteins.
Bacillus thuringiensis (Bt) Naturally occurring soil bacterium that generates a protein toxic
to a variety of lepidoptera, such as corn borers, but is harmless to people and animals.
Bacteriophage Virus that lives in and kills bacteria. Also called phage.
Bacterium Any of a large group of microscopic organisms with a very simple cell structure.
Some manufacture their own food, some live as parasites on other organisms, and some
live on decaying matter.

Bagasse The residue after the extraction of juice from crushed sugarcane stalks.
Base A key component of DNA and RNA molecules. Four different bases are found in
DNA: adenine (A), cytosine (C), guanine (G) and thymine (T). In RNA, uracil (U) substitutes
for thymine. Also known as nitrogenous bases. A base, a phosphate molecule and a sugar
joined together constitute a nucleotide.
Base pair Two nucleotide bases on different strands of the nucleic acid molecule that bond
together. The bases can pair in only one way: adenine with thymine (DNA), or uracil (RNA)
and guanine with cytosine.
Bioassay Determination of the effectiveness of a compound by measuring its effect on
animals, tissues or organisms in comparison with a standard preparation.
Bioaugmentation Increasing the activity of bacteria that break down pollutants by adding
more of their kind. A technique used in bioremediation.
Biocatalyst In bioprocessing, an enzyme that activates or speeds up a biochemical
reaction.
Biochemical The product of a chemical reaction in a living organism.
Biochip An electronic device that uses organic molecules to form a semiconductor.
Bioconversion Chemical restructuring of raw materials by using a biocatalyst.
Biodegradable Capable of being reduced to water and carbon dioxide by the action of
microorganisms.
Bioenrichment A bioremediation strategy that involves adding nutrients or oxygen, thereby
bolstering the activity of microbes as they break down pollutants.
Biofuel Transportation fuel derived from renewable resources such as grain, plant biomass
and treated municipal and industrial waste.
Bioinformatics The science of informatics as applied to biological research. Informatics is
the management and analysis of data using advanced computing techniques.
Bioinformatics is particularly important as an adjunct to genomics research, because of the
large amount of complex data this research generates.
Biolistic device A device that shoots microscopic DNA-coated particles into target cells.
Biological oxygen demand The amount of oxygen used for growth by organisms in water
that contains organic matter.
Biologic A therapeutic or prophylactic derived from a living source (human, animal or
unicellular). Most biologics are complex mixtures that are not easily identified or
characterized, and many are manufactured using biotechnology. Biological products often
represent the cutting-edge of biomedical research and are sometimes the most effective
way to prevent or treat a disease.
Biologic response modifier A substance that alters the growth or functioning of a cell.
Includes hormones and compounds that affect the nervous and immune systems.

Biomass The totality of biological matter in a given area. As commonly used in

biotechnology, refers to the use of cellulose, a renewable resource, for the production of
chemicals that can be used to generate energy or as alternative feedstocks for the chemical
industry to reduce dependence on nonrenewable fossil fuels.
Biomaterials Biological molecules, such as proteins and complex sugars, used to make
medical devices, including structural elements used in reconstructive surgery.
Bioplastics Green plastics manufactured using biopolymers; they are usually
biodegradable. Bioplastics are derived from plant sources such as hemp oil, soybean oil
and corn starch (unlike traditional plastics that are derived from petroleum).
Biopolymers Special class of polymers, such as starch, proteins and peptides, produced
by living organisms in which the monomer units, respectively, are sugars, amino acids and
nucleic acids. Often synonymous with bioplastics.
Biological control The human use of living organisms or viruses to control pest (plant or
animal) populations.
Bioprocess A process in which living cells, or components thereof, are used to produce a
desired product.
Bioreactor Vessel used for bioprocessing.
Biorefinery A facility that integrates biomass conversion processes and equipment to
produce fuels, power, valueadded chemicals and bioplastics.
Bioremediation The use of microorganisms to remedy environmental problems, rendering
hazardous wastes nonhazardous.
Biosynthesis Production of a chemical by a living organism.
Biotechnology The use of biological processes to solve problems or make useful products.
Biotransformation The use of enzymes in chemical synthesis to produce chemical
compounds of a desired stereochemistry.
Blastocyst (Blastula) The 4- to 5-day-old ball of undifferentiated cells from which a
prospective embryo develops. In mammals it consists of two distinct parts: the inner cell
mass and the trophoblast.
B lymphocytes (B-cells) A class of lymphocytes, released from the bone marrow, that
produce antibodies.
Bovine somatotropin (BST) A hormone secreted by the bovine pituitary gland. It is used
to increase milk production by improving the feed efficiency in dairy cattle milk. Also called
bovine growth hormone.
BRCA1 and BRCA2 (BReast CAncer genes 1 and 2) Two genes that normally help to
restrain cell growth, but which can contain certain genetic mutations associated with the
development of breast and ovarian cancer. Note, however, that inherited BRCA1 and
BRCA2 mutations are thought to account for less than 10 percent of all breast and ovarian

cancers. Recent evidence suggests that somatic cell genetic mutations (i.e., noninherited
genetic mutations) in these two genes may also play a role in the development of cancer.
C
Callus A cluster of undifferentiated plant cells that can, in some species, be induced to form
the whole plant.
Carbohydrate A type of biological molecule composed of simple sugars such as glucose.
Common examples include starch and cellulose.
Carcinogen Cancer-causing agent.
Catalyst An agent (such as an enzyme or a metallic complex) that facilitates a reaction but
is not itself changed during the reaction.
Cell The smallest structural unit of a living organism that can grow and reproduce
independently.
Cell culture Growth of cells under laboratory conditions.
Cell differentiation The process by which descendants of a common parental cell achieve
specialized structure and function.
Cell fusion See Fusion.
Cell line Cells that grow and replicate continuously outside the living organism.
Cell-mediated immunity Acquired immunity in which T lymphocytes play a predominant
role. Development of the thymus in early life is critical to the proper development and
functioning of cell-mediated immunity.
Cellulase A class of enzymes produced by fungi, bacteria, plants and animals that converts
cellulose to sugar.
Cellulose A complex carbohydrate that is composed of glucose units and forms the primary
structural component of green plants.
Cellulosic ethanol Ethanol fuel produced through enzymatic hydrolysis from a wide
variety of cellulosic biomass feedstocks including agricultural plant wastes (corn stover,
cereal straws, sugarcane bagasse), plant wastes from industrial processes (sawdust, paper
pulp) and energy crops grown specifically for fuel production (switchgrass).
Chemical genomics Using structural and functional genomic information about biological
molecules, especially proteins, to identify useful small molecules and alter their structure to
improve their efficacy.
Chemical synthesis Purposeful physical and chemical manipulations, usually involving
one or more reactions, in order to get a product or products.
Chimera The individual (animal or lower organism) produced by grafting an embryonic part
of one individual onto an embryo of either the same or a different species.

Chromosomes Threadlike components in the cell that contain DNA and proteins. Genes
are carried on the chromosomes.
Clinical studies Human studies that are designed to measure the efficacy of a new drug or
biologic. Clinical studies routinely involve the use of a control group of patients that is given
an inactive substance (placebo) that looks like the test product.
Clone A term that is applied to genes, cells or entire organisms that are derived fromand
are genetically identical toa single common ancestor gene, cell or organism, respectively.
Cloning of genes and cells to create many copies in the laboratory is a common procedure
essential for biomedical research. Note that several processes commonly described as cell
cloning give rise to cells that are almost but not completely genetically identical to the
ancestor cell. Cloning of organisms from embryonic cells occurs in nature (e.g., identical
twins). Researchers have achieved laboratory cloning using genetic material from adult
animals of several species, including mice, pigs and sheep.
Codon A sequence of three nucleotide bases that specifies an amino acid or represents a
signal to stop or start a function.
Co-enzyme An organic compound that is necessary for the functioning of an enzyme. Co-
enzymes are smaller than the enzymes themselves and sometimes separable from them.
Co-factor A nonprotein substance required for certain enzymes to function. Co-factors can
be co-enzymes or metallic ions.
Colony-stimulating factors (CSFs) A group of lymphokines that induce the maturation
and proliferation of white blood cells from the primitive cell types present in bone marrow.
Combinatorial chemistry A product discovery technique that uses robotics and parallel
synthesis to generate and screen quickly as many as several million molecules with similar
structure in order to find chemical molecules with desired properties.
Co-metabolism A microbe oxidizing not only its main energy source but also another
organic compound.
Complementarity The relationship of the nucleotide bases on two different strands of DNA
or RNA. When the bases are paired properly (adenine with thymine [DNA] or uracil [RNA];
guanine with cytosine), the strands are complementary.
Complementary DNA (cDNA) DNA synthesized from a messenger RNA rather than from a
DNA template. This type of DNA is used for cloning or as a DNA probe for locating specific
genes in DNA hybridization studies.
Computational biology A subdiscipline within bioinformatics concerned with computation-
based research devoted to understanding basic biological processes.
Conjugation Sexual reproduction of bacterial cells in which there is a one-way exchange of
genetic material between the cells in contact.
Corn stover The leaves and stalks of maize plants usually left in a field after harvest.
Crossing over Exchange of genes between two paired chromosomes.

Cross-licensing Legal, contractual procedure in which two or more firms with competing,
similar technologies and possible conflicting patent claims strike a deal to reduce the need
for legal actions to clarify who is to profit from applications of the technology.
Culture As a noun, cultivation of living organisms in prepared medium; as a verb, to grow in
prepared medium.
Culture medium Any nutrient system for the artificial cultivation of bacteria or other cells;
usually a complex mixture of organic and inorganic materials.
Cyto- Referring to cell.
Cytogenetics Study of the cell and its heredity-related components, especially
chromosomes.
Cytoplasm Cellular material that is within the cell membrane and surrounds the nucleus.
Cytotoxic Able to cause cell death.
D
Deoxyribonucleic acid (DNA) The molecule that carries the genetic information for most
living systems. The DNA molecule consists of four bases (adenine, cytosine, guanine and
thymine) and a sugar-phosphate backbone, arranged in two connected strands to form a
double helix.
Differentiation The process of biochemical and structural changes by which cells become
specialized in form and function.
Diploid A cell with two complete sets of chromosomes.
DNA See Deoxyribonucleic acid.
DNA chip A small piece of glass or silicon that has small pieces of DNA arrayed on its
surface.
DNA fingerprinting The use of restriction enzymes to measure the genetic variation of
individuals. This technology is often used as a forensic tool to detect differences or
similarities in blood and tissue samples at crime scenes.
DNA hybridization The formation of a double-stranded nucleic acid molecule from two
separate strands. The term also applies to a molecular technique that uses one nucleic acid
strand to locate another.
DNA library A collection of cloned DNA fragments that collectively represent the genome of
an organism.
DNA polymerase An enzyme that replicates DNA. DNA polymerase is the basis of PCR
the polymerase chain reaction.
DNA probe A small piece of nucleic acid that has been labeled with a radioactive isotope,
dye or enzyme and is used to locate a particular nucleotide sequence or gene on a DNA
molecule.

DNA repair enzymes Proteins that recognize and repair certain abnormalities in DNA.
DNA sequence The order of nucleotide bases in the DNA molecule.
DNA vaccines Pieces of foreign DNA that are injected into an organism to trigger an
immune response.
Double-blind trial A clinical trial in which neither the patient nor the health care provider
knows whether the drug or placebo is being administered.
Double helix A term often used to describe the configuration of the DNA molecule. The
helix consists of two spiraling strands of nucleotides (a sugar, phosphate and base) joined
crosswise by specific pairing of the bases. See Deoxyribonucleic acid; Base; Base pair.
Diagnostic A product used for the diagnosis of disease or medical condition. Both
monoclonal antibodies and DNA probes are useful diagnostic products
Drug delivery The process by which a formulated drug is administered to the patient.
Traditional routes have been oral or intravenous perfusion. New methods deliver through
the
skin with a transdermal patch or across the nasal membrane with an aerosol spray.
E
Electrophoresis A technique for separating different types of molecules based on their
patterns of movement in an electrical field.
Electroporation The creation of reversible small holes in a cell wall or membrane through
which foreign DNA can pass. This DNA can then integrate into the cells genome.
Enzyme-linked immunosorbent assay (ELISA) A technique for detecting specific proteins
by using antibodies linked to enzymes.
Embryonic stem cells Cells that can give rise to any type of differentiated cell. They can
be derived from two sources: the inner cell mass from a blastocyst or the primordial germ
cells (eggs and sperm) of an older embryo.
Endostatin An endogenous protein that blocks the proliferation of blood vessels.
Endpoints A clinical trials outcome measures (such as tumor shrinkage viral clearance, or
survival).
Environmental biotechnology The process of using cells or cell components to prevent or
clean up pollution.
Enzymatic hydrolysis The process by which enzymes are used to catalytically convert
starch or cellulose into sugar.
Enzyme A protein catalyst that facilitates specific chemical or metabolic reactions
necessary for cell growth and reproduction.

Erythropoietin (EPO) A protein that boosts production of red blood cells. It is clinically
useful in treating certain types of anemia.
Escherichia coli (E. coli) A bacterium that inhabits the intestinal tract of most vertebrates.
Much of the work using recombinant DNA techniques has been carried out with this
organism because it has been genetically well characterized.
Eukaryote A cell or organism containing a true nucleus, with a well-defined membrane
surrounding the nucleus. All organisms except bacteria, viruses and cyanobacteria are
eukaryotic. Compare Prokaryote.
Exon In eukaryotic cells, that part of the gene that is transcribed into messenger RNA and
encodes a protein. See Intron; Splicing.
Expression In genetics, manifestation of a characteristic that is specified by a gene. With
hereditary disease, for example, a person can carry the gene for the disease but not
actually
have the disease. In this case, the gene is present but not expressed. In industrial
biotechnology, the term is often used to mean the production of a protein by a gene that
has been inserted into a new host organism.
Extremophiles Microorganisms that live at extreme levels of pH, temperature, pressure
and salinity.
F
Factor VIII A large, complex protein that aids in blood clotting and is used to treat
hemophilia. See Antihemophilic factors.
Feedstock The raw material used for chemical or biological processes.
Fermentation The process of growing microorganisms for the production of various
chemical or pharmaceutical compounds. Microbes are normally incubated under specific
conditions in the presence of nutrients in large tanks called fermentors.
Functional foods Foods containing compounds with beneficial health effects beyond those
provided by the basic nutrients, minerals and vitamins. Also called nutraceuticals.
Functional genomics A field of research that aims to understand what each gene does,
how it is regulated and how it interacts with other genes.
Fusion Joining of the membrane of two cells, thus creating a daughter cell that contains
some of the same properties from each parent cells. Used in making hybridomas.
G
Gel electrophoresis A process for separating molecules by forcing them to migrate
through a gel under the influence of an electric field.

Gene A segment of chromosome. Some genes direct the syntheses of proteins, while
others have regulatory functions. See Operator gene; Structural gene; Suppressor gene.
Gene amplification The increase, within a cell, of the number of copies of a given gene.
Gene knockout The replacement of a normal gene with a mutated form of the gene by
using homologous recombination. Used to study gene function.
Gene machine A computerized device for synthesizing genes by combing nucleotides
(bases) in the proper order.
Gene mapping Determination of the relative locations of genes on a chromosome.
Gene sequencing Determination of the sequence of nucleotide bases in a strand of DNA.
See Sequencing.
Gene therapy The replacement of a defective gene in an organism suffering from a genetic
disease. Recombinant DNA techniques are used to isolate the functioning gene and insert it
into cells. More than 300 single-gene genetic disorders have been identified in humans. A
significant percentage of these may be amenable to gene therapy.
Genetic code The code by which genetic information in DNA is translated into biological
function. A set of three nucleotides (codon), the building blocks of DNA, signifies one amino
acid, the building blocks of proteins.
Genetic modification A number of techniques, such as selective breeding, mutagenesis,
transposon insertions and recombinant DNA technology, that are used to alter the genetic
material of cells in order to make them capable of producing new substances, performing
new functions or blocking the production of substances.
Genetic predisposition Susceptibility to disease that is related to a genetic mutation,
which may or may not result in actual development of the disease.
Genetic screening The use of a specific biological test to screen for inherited diseases or
medical conditions. Testing can be conducted prenatally to check for metabolic defects and
congenital disorders in the developing fetus as well as postnatally to screen for carriers of
heritable diseases.
Genetic testing The analysis of an individuals genetic material. Genetic testing can be
used to gather information on an individuals genetic predisposition to a particular health
condition, or to confirm a diagnosis of genetic disease.
Genetically enhanced microbes (GEMs) Organisms changed through selective breeding,
mutagenesis, transposon insertions or recombinant DNA technology so they can make new
substances or perform new functions.
Genome The total hereditary material of a cell, comprising the entire chromosomal set
found in each nucleus of a given species.
Genomics The study of genes and their function. Recent advances in genomics are
bringing about a revolution in our understanding of the molecular mechanisms of disease,
including the complex interplay of genetic and environmental factors. Genomics is also

stimulating the discovery of breakthrough health-care products by revealing thousands of

new biological targets for the development of drugs and by giving scientists innovative ways
to design new drugs, vaccines and DNA diagnostics. Genomic-based therapeutics may
include traditional small chemical drugs, as well as protein drugs and gene therapy.
Genotype Genetic makeup of an individual or group. Compare Phenotype.
Germ cell Reproductive cell (sperm or egg). Also called gamete or sex cell.
Germplasm The total genetic variability, represented by germ cells or seeds, available to a
particular population of organisms.
Glycoprotein A protein conjugated with a carbohydrate group.
Granulocyte One of three types of white blood cells. Granulocytes digest bacteria and
other parasites.
Granulocyte-macrophage colony stimulating factor
(GMCSF) A natural hormone that stimulates white blood cell production, particularly that of
granulocytes and monocytes (the precursors of macrophages).
Growth factors Naturally occurring proteins that stimulate the growth and reproduction of
specific cell types. Growth factors are essential to regenerative medicine and tissue
engineering.
Growth hormone A protein produced by the pituitary gland that is involved in cell growth.
Human growth hormone is used clinically to treat dwarfism. Various animal growth
hormones can be used to improve milk production as well as produce a leaner variety of
meat.
H
Haploid A cell with half the usual number of chromosomes, or only one chromosome set.
Sex cells are haploid. Compare Diploid.
Hapten The portion of an antigen that determines its immunological specificity. When
coupled to a large protein, a hapten stimulates the formation of antibodies to the
twomolecule
complex. Also called antigenic determinant.
Hemagglutination Clumping (agglutination) of red blood cells. Heredity Transfer of genetic
information from parent cells to progeny.
Histocompatibility Immunologic similarity of tissues such that grafting can be done without
tissue rejection.
Histocompatibility antigen An antigen that causes the rejection of grafted material from
an animal different in genotype from the host animal.
Homeobox Family of genes that regulate activities of other genes (turns genes on and off).

Homologous Corresponding or alike in structure, position or origin.

Hormone A chemical or protein that acts as a messenger or stimulatory signal, relaying
instructions to stop or start certain physiological activities. Hormones are synthesized in one
type of cell and then released to direct the function of other cell types.
Host A cell or organism used for growth of a virus, plasmid or other form of foreign DNA, or
for the production of cloned substances.
Host-vector system Combination of DNA-receiving cells (host) and DNA-transporting
substance (vector) used for introducing foreign DNA into a cell.
Human Genome Project An international research effort aimed at discovering the full
sequence of bases in the human genome. Led in the United States by the National
Institutes of Health and the Department of Energy.
Human immunodeficiency virus (HIV) The virus that causes acquired immune deficiency
syndrome (AIDS).
Hybridization Production of offspring, or hybrids, from genetically dissimilar parents. The
process can be used to produce hybrid plants (by crossbreeding two different varieties) or
hybridomas (hybrid cells formed by fusing two unlike cells, used in producing monoclonal
antibodies). See DNA hybridization.
Hybridoma The cell produced by fusing two cells of different origin. In monoclonal antibody
technology, hybridomas are formed by fusing an immortal cell (one that divides
continuously) and an antibody-producing cell. See also Monoclonal antibody; Myeloma.
Hydrolysis Decomposition of a chemical compound through reaction with water.
I
Immune response The response of the immune system to challenge by a foreign antigen.
Immune serum Blood serum containing antibodies.
Immune system The combination of cells, biological substances (such as antibodies) and
cellular activities that work together to provide resistance to disease.
Immunity Nonsusceptibility to a disease or to the toxic effects of antigenic material. See
Active immunity; Cell-mediated immunity; Natural active immunity; Natural passive
immunity; Passive immunity.
Immunoassay Technique for identifying substances based on the use of antibodies.
Immunodiagnostic The use of specific antibodies to measure a substance. This tool is
useful in diagnosing infectious diseases and the presence of foreign substances in a variety
of human and animal fluids (blood, urine, etc.). The approach is currently being investigated
as a way of locating tumor cells in the body.
Immunofluorescence Technique for identifying antigenic material that uses an antibody
labeled with fluorescent material. Specific binding of the antibody and antigen can be seen

under a microscope by applying ultraviolet light rays and noting the visible light that is
produced.
Immunogen Any substance that can elicit an immune response.
Immunoglobulin General name for proteins that function as antibodies. These proteins
differ somewhat in structure and are grouped into five categories on the basis of these
differences; immunoglobulin G (IgG), IgM, IgA, IgE and IgD.
Immunology Study of all phenomena related to the bodys response to antigenic challenge
(i.e., immunity, sensitivity and allergy).
Immunomodulators A diverse class of proteins that boost the immune system. Many are
cell growth factors that accelerate the production of specific cells that are important in
mounting an immune response in the body. These proteins are being investigated for use in
possible treatments for cancer.
Immunotoxins Specific monoclonal antibodies that have a protein toxin molecule attached.
The monoclonal antibody is targeted against a tumor cell, and the toxin is designed to kill
that cell when the antibody binds to it.
Inducer A molecule or substance that increases the rate of enzyme synthesis, usually by
blocking the action of the corresponding repressor.
In situ In its original or natural place or position.
Industrial biotechnology The process of using the life sciences, enzymes or microbes in
industrial processes or in producing commercial products.
Indication The specific condition a drug aims to treat. An indication may be broad (for
example, type 2 diabetes) or it may be narrower (for example, insulin-dependent type 2
diabetes).
Institutional review board (IRB) Local oversight group at a hospital, university or other
health care facility who ensure trials are conducted ethically and as safely as possible.
Interferon A class of lymphokine proteins important in the immune response. There are
three major types of interferon: alpha (leukocyte), beta (fibroblast) and gamma (immune).
Interferons inhibit viral infections and may have anticancer properties.
Interleukin A type of lymphokine that regulates the growth and development of white blood
cells. Twelve interleukins (IL-1 through IL-12) have been identified to date.
Intron In eukaryotic cells, a sequence of DNA that is contained in the gene but does not
encode for protein. The presence of introns splits the coding region of the gene into
segments called exons. See Exon; Splicing.
Investigational New Drug Application (IND) An application to begin studies of a new drug
or biologic on humans. The IND gives the plan for the study and contains formulation,
manufacturing and animal test result information.
In vitro Literally, in glass. Performed in a test tube or other laboratory apparatus.

In vivo Literally, in the living. Performed in a living organism.

Islet cells Pancreatic cells that are the source of insulin and two other hormones involved
in regulating glucose metabolism and absorption.
Isoenzyme One of the several forms that a given enzyme can take. The forms may differ in
certain physical properties, but function similarly as biocatalysts.
Isogenic Of the same genotype.
K
Kidney plasminogen activator A precursor to the enzyme urokinase, which has blood-
clotting properties.
L
Leukocyte A colorless cell in the blood, lymph and tissues that is an important component
of the bodys immune system. Also called white blood cell.
Life cycle assessment (LCA) A systematic technique for identifying and evaluating the
potential environmental benefit and impact of products or processes.
Library A set of cloned DNA fragments that taken collectively contain the entire genome of
an organism. Also called a DNA library.
Ligase An enzyme used to join DNA or RNA segments together.
Linkage The tendency for certain genes to be inherited together due to their physical
proximity on the chromosome.
Linker A fragment of DNA with a restriction site that can be used to join DNA strands.
Lipoproteins A class of serum proteins that transport lipids and cholesterol in the
bloodstream. Abnormalities in lipoprotein metabolism have been implicated in certain heart
diseases.
Lymphocyte A type of leukocyte found in lymphatic tissue in the blood, lymph nodes and
organs. Lymphocytes are continuously made in the bone marrow and mature into antibody-
forming cells. See B lymphocytes; T lymphocytes.
Lymphokine A class of soluble proteins produced by white blood cells that play a role, as
yet not fully understood, in the immune response. See Interferon; Interleukin.
Lymphoma Form of cancer that affects the lymph tissue.
M
Macrophage A type of white blood cell produced in blood vessels and loose connective
tissues that can ingest dead tissues and cells and is involved in producing interleukin-1.
When exposed to the lymphokine macrophage-activating factor, macrophages also kill
tumor cells. See Phagocyte.

Macrophage colony stimulating factor (M-CSF) A natural hormone that stimulates the
production of white blood cells, particularly monocytes (the precursors of macrophages).
Medium A substance containing nutrients needed for cell growth.
Meiosis Process of cell reproduction whereby the daughter cells have half the chromosome
number of the parent cells. Sex cells are formed by meiosis. Compare Mitosis.
Messenger RNA (mRNA) Nucleic acid that carries instructions to a ribosome for the
synthesis of a particular protein.
Metabolism All biochemical activities carried out by an organism to maintain life.
Microbial herbicides and pesticides Microorganisms that are toxic to specific plants or
insects. Because of their narrow host range and limited toxicity, these microorganisms may
be preferable to their chemical counterparts for certain pestcontrol applications.
Microbiology Study of living organisms that can be seen only under a microscope.
Microinjection The injection of DNA using a very fine needle into a cell.
Microorganism Any organism that can be seen only with the aid of a microscope. Also
called microbe.
Mitosis Process of cell reproduction whereby the daughter cells are identical in
chromosome number to the parent cells. Compare Meiosis.
Molecular genetics Study of how genes function to control cellular activities.
Monoclonal antibody (MAb) Highly specific, purified antibody that is derived from only one
clone of cells and recognizes only one antigen. See Hybridoma; Myeloma.
Monocytes One of three types of white blood cells. Monocytes are precursors to
macrophages.
Multigenic Of hereditary characteristics, one that is specified by several genes.
Mutagen A substance that induces mutations.
Mutant A cell that manifests new characteristics due to a change in its DNA.
Mutation A change in the genetic material of a cell.
Myeloma A type of cancer cell (plasma cell) that is used in monoclonal antibody technology
to form hybridomas.
N
Nanobiotechnology The merger of biotechnology and nanotechnology to build or
manipulate matter at a molecular level.
Nanotechnology The engineering of functional systems at the molecular scale; also, a
branch of science that proposes the manipulation of single atoms.
Natural active immunity Immunity that is established after the occurrence of a disease.

Natural killer (NK) cell A type of leukocyte that attacks cancerous or virus-infected cells
without previous exposure to the antigen. NK cell activity is stimulated by interferon.
Natural passive immunity Immunity conferred by the mother on the fetus or newborn.
Nitrogen fixation A biological process (usually associated with plants) whereby certain
bacteria convert nitrogen in the air to ammonia, thus forming a nutrient essential for plant
growth.
Nitrogenous base See Base.
Noncoding DNA DNA that does not encode any product (RNA or protein). The majority of
the DNA in plants and animals is noncoding.
Nuclease An enzyme that, by cleaving chemical bonds, breaks down nucleic acids into
their constituent nucleotides.
Nucleic acids Large molecules, generally found in the cells nucleus and/or cytoplasm, that
are made up of nucleotides. The two most common nucleic acids are DNA and RNA.
Nucleotides The building blocks of nucleic acids. Each nucleotide is composed of sugar,
phosphate and one of four nitrogen bases. The sugar in DNA is deoxyribose and RNAs
sugar is ribose. The sequence of the bases within the nucleic acid determines the
sequence of amino acids in a protein. See Base.
Nucleus The structure within eukaryotic cells that contains chromosomal DNA.
O
Oligonucleotide A polymer consisting of a small number (about two to 10) of nucleotides.
Oncogene Gene thought to be capable of producing cancer.
Oncogenic Cancer causing.
Oncology Study of cancer.
Operator gene A region of the chromosome, adjacent to the operon, where a repressor
protein binds to prevent transcription of the operon.
Operon Sequence of genes responsible for synthesizing the enzymes needed for
biosynthesis of a molecule.
Organic compound A compound containing carbon.
P
Parthenogenesis Asexual reproduction achieved with only a female gamete; this form of
reproduction is more common in plants and invertebrate animals.
Passive immunity Immunity acquired from receiving preformed antibodies.
Pathogen Disease-causing organism.

Peptide Two or more amino acids joined by a linkage called a peptide bond.
Personalized medicine The use of individual molecular (often genetic) information to
prevent disease, choose medicines and make other critical decisions about health.
Phagocyte A type of white blood cell that can ingest invading microorganisms and other
foreign material. See Macrophage.
Pharmacogenomics The science that examines the inherited variations in genes that
dictate drug response and explores the ways these variations can be used to predict
whether a patient will have a good response to a drug, a bad response to a drug, or no
response at all. See Pharmacogenetics.
Pharmacogenetics The study of inherited differences (variation) in drug metabolism and
response. See Pharmacogenomics.
Phenotype Observable characteristics resulting from interaction between an organisms
genetic makeup and the environment. Compare Genotype.
Photosynthesis Conversion by plants of light energy into chemical energy, which is then
used to support the plants biological processes.
Phytoremediation The use of plants to clean up pollution.
Plasma The fluid (noncellular) fraction of blood.
Plasmapheresis A technique used to separate useful factors from blood.
Plasmid A small circular form of DNA that carries certain genes and is capable of
replicating independently in a host cell.
Pluripotent cells Having the capacity to become any kind of cell or tissue in the body.
Embryonic stem cells and cells of the inner cell mass are pluripotent. Adult stem cells are
multipotent. The mammalian embryo (blastocyst trophoblast plus inner cell mass) is
totipotent because it can become an entire organism. Fully differentiated cells from many
plants are totipotent.
Polyclonal Derived from different types of cells.
Polyhydroxyalkanoates (PHAs) Linear polyesters (plastics) produced in nature by
bacterial fermentation of sugar or lipids.
Polylactide (PLA) A biodegradable, thermoplastic, aliphatic polyester derived from
renewable resources, with corn starch or sugarcane serving as common feedstocks.
Polymer A long molecule of repeated subunits.
Polymerase General term for enzymes that carry out the synthesis of nucleic acids.
Polymerase chain reaction (PCR) A technique to amplify a target DNA sequence of
nucleotides by several hundred thousandfold.
Polypeptide Long chain of amino acids joined by peptide bonds.

Preclinical studies Studies that test a drug on animals and in other nonhuman test
systems. Safety information from such studies is used to support an investigational new
drug application (IND).
Pretreatment A process that renders plant matter more susceptible to enzyme breakdown.
Prokaryote An organism (e.g., bacterium, virus, cyanobacterium) whose DNA is not
enclosed within a nuclear membrane. Compare Eukaryote.
Promoter A DNA sequence that is located in front of a gene and controls gene expression.
Promoters are required for binding of RNA polymerase to initiate transcription.
Prophage Phage nucleic acid that is incorporated into the hosts chromosome but does not
cause cell lysis.
Protein A molecule composed of amino acids. There are many types of proteins, all
carrying out different functions essential for cell growth.
Protein A A protein produced by the bacterium Staphylococcus aureus that specifically
binds antibodies. It is useful in the purification of monoclonal antibodies.
Protein production A process that covers all aspects of protein formation from gene
expression to the production of the final product.
Proteome The entire complement of proteins expressed by a genome, cell, tissue or
organism; the protein complement of an organism coded for by its genome. Each cell
produces thousands of proteins, each with a specific function. This collection of proteins in
a cell is known as the proteome (from protein and genome). Unlike the genome, which is
constant irrespective of cell type, the proteome varies from one cell type to the next.
Proteomics The science of proteomics attempts to identify the protein profile of various cell
types, assess protein differences between healthy and diseased cells, and uncover not only
each proteins specific function but also how it interacts with other proteins.
Protoplast The cellular material that remains after the cell wall has been removed from
plant and fungal cells.
Pure culture In vitro growth of only one type of microorganism.
R
Radioimmunoassay (RIA) A test combining radioisotopes and immunology to detect trace
substances. Such tests are useful for studying antibody interactions with cell receptors, and
can be developed into clinical diagnostics.
Rational drug design Using the known three-dimensional structure of a molecule, usually
a protein, to design a drug molecule that will bind to it. Usually viewed as an alternative to
drug discovery through screening many molecules for biological activity.
Reagent Substance used in a chemical reaction.
Recombinant DNA (rDNA) The DNA formed by combining segments of DNA from two
different sources.

Regeneration Laboratory technique for forming a new plant from a clump of plant cells.
Regulatory gene A gene that acts to control the proteinsynthesizing activity of other genes.
Replication Reproduction or duplication, as of an exact copy of a strand of DNA.
Replicon A segment of DNA (e.g., chromosome or plasmid) that can replicate
independently.
Repressor A protein that binds to an operator adjacent to a structural gene, inhibiting
transcription of that gene.
Restriction enzyme An enzyme that breaks DNA in highly specific locations, creating gaps
into which new genes can be inserted.
Restriction fragment length polymorphism (RFLP) The variation in the length of DNA
fragments produced by a restriction endonuclease that cuts at a polymorphic locus. This is
a key tool in DNA fingerprinting and is based on the presence of different alleles in an
individual. RFLP mapping is also used in plant breeding to see if a key trait such as disease
resistance is inherited.
Reticuloendothelial system The system of macrophages, which serves as an important
defense system against disease.
Retrovirus A virus that contains the enzyme reverse transcriptase. This enzyme converts
the viral RNA into DNA, which can combine with the DNA of the host cell and produce more
viral particles.
Rheology Study of the flow of matter such as fermentation liquids.
Rhizobium A class of microorganisms that converts atmospheric nitrogen into a form that
plants can utilize for growth. Species of this microorganism grow symbiotically on the roots
of certain legumes, such as peas, beans and alfalfa.
Ribonucleic acid (RNA) A molecule similar to DNA that delivers DNAs genetic message
to the cytoplasm of a cell where proteins are made.
Ribosome A cellular component, containing protein and RNA, that is involved in protein
synthesis.
RNA interference A natural process used by organisms to block protein production.
S
Saccharification The hydrolysis of cellulose or starch into glucose.
Scale-up Transition from small-scale production to production of large industrial quantities.
Selective medium Nutrient material constituted such that it will support the growth of
specific organisms while inhibiting the growth of others.
Sepsis The presence in the blood or other tissues of pathogenic microorganisms or their
toxins; the condition associated with such presence.

Sequencing Decoding a strand of DNA or gene into the specific order of its nucleotides:
adenine, cytosine, guanine and thymine. This analysis can be done manually or with
automated equipment. Sequencing a gene requires analyzing an average of 40,000
nucleotides.
Serology Study of blood serum and reactions between the antibodies and antigens therein.
Single-blind trial A clinical trial in which the health care provider knows whether the patient
is receiving the placebo or active drug, but the patient does not.
Single-cell protein Cells or protein extracts from microorganisms, grown in large quantities
for use as protein supplements.
Somatic cells Cells other than sex or germ cells.
Somatic cell gene therapy Somatic cell gene therapy involves the insertion of genes into
cells for therapeutic purposes; for example, to induce the treated cells to produce a protein
that the body is missing. It does not affect genetic makeup of a patients offspring and
generally does not change all, or even most, cells in the recipient. Somatic cell gene
therapy is only one way of applying the science of genomics to improve health care.
Somatic cell nuclear transfer The transfer of a nucleus from a fully differentiated cell into
an egg that has had its nucleus removed.
Splicing The removal of introns and joining of exons to form a continuous coding sequence
in RNA.
Starch ethanol Ethanol produced from the starch in fruit and seeds.
Stop codon One of three codons in messenger RNA that signal the end of the amino acid
chain in protein synthesis.
Structural gene A gene that codes for a protein, such as an enzyme.
Substrate Material acted on by an enzyme.
Suicide gene A gene that codes for an antibiotic that can kill the host bacterial cell. It is
genetically modified into the bacterium along with a molecular switch that is controlled by a
nutrient in the environment. When the nutrient disappears, the suicide gene is switched on
and the bacterium dies.
Suppressor gene A gene that can reverse the effect of a mutation in other genes.
Systems biology A hypothesis-driven field of research that creates predictive
mathematical models of complex biological processes or organ systems.
Switchgrass A bunch grass that is a good candidate for biofuel due to its hardiness, rapid
growth and low fertilization and herbicide requirements.
T
Technology transfer The process of transferring discoveries made by basic research
institutions, such as universities and government laboratories, to the commercial sector for
development into useful products and services.

Template A molecule that serves as the pattern for synthesizing another molecule.
Terminator Sequence of DNA bases that tells the RNA polymerase to stop synthesizing
RNA.
Tertiary structure The total three-dimensional shape of a protein that is essential to protein
function.
Therapeutics Compounds that are used to treat specific diseases or medical conditions.
Thymus A lymphoid organ in the lower neck, the proper functioning of which in early life is
necessary for development of the immune system.
Tissue culture In vitro growth in nutrient medium of cells isolated from tissue.
Tissue plasminogen activator (tPA) A protein produced in small amounts in the body that
aids in dissolving blood clots.
T lymphocytes (T-cells) White blood cells that are produced in the bone marrow but
mature in the thymus. They are important in the bodys defense against certain bacteria and
fungi, help B lymphocytes make antibodies and help in the recognition and rejection of
foreign tissues. T lymphocytes may also be important in the bodys defense against
cancers.
Toxin A poisonous substance produced by certain microorganisms or plants.
Transcription Synthesis of messenger (or any other) RNA on a DNA template.
Transdifferentiation The process whereby a specialized cell dedifferentiates and re-
differentiates into a different cell type; or the process whereby an adult stem cell from a
specific tissue type becomes a cell type from a very different tissue (for example, a nerve
stem cell differentiates into a kidney cell).
Transduction Transfer of genetic material from one cell to another by means of a virus or
phage vector.
Transfection Infection of a cell with nucleic acid from a virus, resulting in replication of the
complete virus.
Transfer RNA (tRNA) RNA molecules that carry amino acids to sites on ribosomes where
proteins are synthesized.
Transformation Change in the genetic structure of an organism by the incorporation of
foreign DNA.
Transgenic organism An organism formed by the insertion of foreign genetic material into
the germ line cells of organisms. Recombinant DNA techniques are commonly used to
produce transgenic organisms.
Translation Process by which the information on a messenger RNA molecule is used to
direct the synthesis of a protein.
Transposon A segment of DNA that can move around and be inserted at several sites in
bacterial DNA or in a phage, thus alerting the hosts DNA.

Tumor necrosis factors (TNFs) Rare proteins of the immune system that appear to
destroy some types of tumor cells without affecting healthy cells.
V
Vaccine A preparation that contains an antigen, consisting of whole disease-causing
organisms (killed or weakened) or parts of such organisms, that is used to confer immunity
against the disease that the organisms cause. Vaccine preparations can be natural,
synthetic or derived by recombinant DNA technology.
Vector The agent (e.g., plasmid or virus) used to carry new DNA into a cell.
Virion An elementary viral particle consisting of genetic material and a protein covering.
Virology Study of viruses.
Virulence Ability to infect or cause disease.
Virus A submicroscopic organism that contains genetic information but cannot reproduce
itself. To replicate, it must invade another cell and use parts of that cells reproductive
machinery.
W
White biotechnology European term for industrial biotechnology.
White blood cells Leukocytes.
Wild type The form of an organism that occurs most frequently in nature.
X
X-ray crystallography An essential technique for determining the three-dimensional
structure of biological molecules. This information aids in the discovery of products that will
interact with the biological molecule.
Xenobiotics Synthetic chemicals believed to be resistant to environmental degradation. A
branch of biotechnology called bioremediation is seeking to develop biological methods to
degrade such compounds.
Xenotransplantation The transplantation of living organs, cells or tissues from animals into
humans.
Y
Yeast A general term for single-celled fungi that reproduce by budding. Some yeasts can
ferment carbohydrates (starches and sugars) and thus are important in brewing and baking.

Annexure - h
References
1. ^ "The Convention on Biological Diversity (Article 2. Use of Terms)." United Nations. 1992. Retrieved
on February 6, 2008.
2. ^ Bunders, J.; Haverkort, W.; Hiemstra, W. "Biotechnology: Building on Farmer's Knowledge." 1996,
Macmillan Education, Ltd. ISBN 0333670825
3. ^ "Diamond v. Chakrabarty, 447 U.S. 303 (1980). No. 79-139." United States Supreme Court. June 16,
1980. Retrieved on May 4, 2007.
4. ^ The Recession List - Top 10 Industries to Fly and Fl... (ith anincreasing share accounted for by ...)
5. ^ Gerstein, M. "Bioinformatics Introduction." Yale University. Retrieved on May 8, 2007.
6. ^ W. Bains, Genetic Engineering For Almost Everybody: What Does It Do? What Will It Do? (London:
Penguin Books, 1987), 99.
a b c
7. ^ U.S. Department of State International Information Programs, Frequently Asked Questions
About Biotechnology, USIS Online; available from
http://usinfo.state.gov/ei/economic_issues/biotechnology/biotech_faq.html, accessed 13 Sept 2007. Cf.
C. Feldbaum, Some History Should Be Repeated, 295 Science, 8 February 2002, 975.
8. ^ http://www.cartercenter.org/news/documents/doc32.html
This op-ed appeared in the July 11, 1997, edition of The Washington Times
9. ^ Asian Development Bank, Agricultural Biotechnology, Poverty Reduction and Food Security (Manila:
Asian Development Bank, 2001). Also available from http://www.adb.org
a b
10. ^ D. Bruce and A. Bruce, Engineering Genesis: The Ethics of Genetic Engineering, London:
Earthscan Publications, 1999
11. ^ S. Abdulla. Drought Stress Nature: Science Update; available from http://www.nature.com/ nsu;
accessed 3 May 2002.
12. ^ National Academy of Sciences. Transgenic Plants and World Agriculture (Washington: National
Academy Press, 2001)
13. ^ For an account of the research and development of Flavr Savr tomato, see B. Martineau, First
Fruit: The Creation of the Flavr Savr Tomato and the Birth of Biotech Food (New York: McGraw-Hill,
2001)
14. ^ A.F. Krattiger, An Overview of ISAAA from 1992 to 2000, ISAAA Brief No. 19-2000, 9
15. ^ EuropaBio - An animal friendly alternative for cheeze makers
16. ^ EuropaBio - Biologically better bread
17. ^ L. P. Gianessi, C. S. Silvers, S. Sankula and J. E. Carpenter. Plant Biotechnology: Current and
Potential Impact for Improving Pest management in US Agriculture, An Analysis of 40 Case Studies
(Washington, D.C.: National Center for Food and Agricultural Policy, 2002), 5-6
18. ^ Pascual DW (2007). "Vaccines are for dinner". Proc Natl Acad Sci U S a 104 (26): 107578.
doi:10.1073/pnas.0704516104. PMID 17581867. http://www.pnas.org/cgi/content/full/104/26/10757.
19. ^ Diaz E (editor). (2008). Microbial Biodegradation: Genomics and Molecular Biology (1st ed. ed.).
Caister Academic Press. ISBN 978-1-904455-17-2. http://www.horizonpress.com/biod.
20. ^ Martins VAP et al (2008). "Genomic Insights into Oil Biodegradation in Marine Systems". Microbial
Biodegradation: Genomics and Molecular Biology. Caister Academic Press. ISBN 978-1-904455-17-2.
21. Guide to Biotechnology 2008

Annexure - i
Bio-safety Regulations
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DEVELOPMENT &

National Commission on Biotechnology

NCB Consultant Report Page 2

NCB Consultant Report Page 3

15. ANNEXURES ................................................................................. 90

NCB Consultant Report Page 4

In order to achieve this objective, National Commission on Biotechnology hired this

The project consultant wishes to thank the staff of National Commission on

NCB Consultant Report Page 5

NCB Consultant Report Page 6

NCB Consultant Report Page 7

is therefore essential that it should dedicatedly encourage and support research

NCB Consultant Report Page 8

PAKISTAN'S DEVELOPMENT PROGRESS

NCB Consultant Report Page 9

Magnitude of Population and its implications for health and

NCB Consultant Report Page 10

Biotechnology is the technology based on biology, especially when used in

NCB Consultant Report Page 11

NCB Consultant Report Page 12

Recombinant DNA Technology

NCB Consultant Report Page 13

THE POWER OF BIOTECHNOLOGY

NCB Consultant Report Page 14

NCB Consultant Report Page 15

consume less in resources than conventional processes used to manufacture

Biopharmaceuticals are large biological molecules known as proteins and these

NCB Consultant Report Page 16

NCB Consultant Report Page 17

Vaccine Delivery Systems

NCB Consultant Report Page 18

RECOMBINANT PROTEIN Therapeutics

NCB Consultant Report Page 19

NCB Consultant Report Page 20

Increased nutritional qualities & quantity of food crops

NCB Consultant Report Page 21

Reduced dependence on fertilizers, pesticides and other

Production of novel substances in crop plants

NCB Consultant Report Page 22

Industrial biotechnology is making manufacturing processes more efficient in many

Some of the industrial applications of biotechnology are:

Biocatalysts (Industrial Enzymes)

NCB Consultant Report Page 23

extraordinary properties of biological molecules and cell processes,

BIOREMEDIATION AND BIODEGRADATION

NCB Consultant Report Page 24

well as clues to the evolution of degradation pathways and to the molecular

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USING NEW KNOWLEDGE TO DEVELOP PRODUCTS

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Increased competition has also placed pressure on the time-to-market, generating a

Drug Discovery Process

The net result is considerable pressure to streamline the development and

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The biopharmaceutical development process

Lab & Animal Testing

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