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7.23A: Overview of Biotechnology - Biology

7.23A:  Overview of Biotechnology - Biology


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Biotechnology is the use of biological techniques and engineered organisms to make products or plants and animals that have desired traits.

Learning Objectives

  • Describe the historical development of biotechnology

Key Points

  • For thousands of years, humankind has used biotechnology in agriculture, food production, and medicine.
  • In the late 20th and early 21st century, biotechnology has expanded to include new and diverse sciences such as genomics, recombinant gene technologies, applied immunology, and development of pharmaceutical therapies and diganostic tests.
  • Biotechnology has applications in four major 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, biofuels), and environmental uses.

Key Terms

  • nanotechnology: the science and technology of creating nanoparticles and of manufacturing machines which have sizes within the range of nanometres

People have used biotechnology processes, such as selectively breeding animals and fermentation, for thousands of years. Late 19th and early 20thcentury discoveries of how microorganisms carry out commercially useful processes and how they cause disease led to the commercial production of vaccines and antibiotics. Improved methods for animal breeding have also resulted from these efforts. Scientists in the San Francisco Bay Area took a giant step forward with the discovery and development of recombinant DNA techniques in the 1970s. The field of biotechnology continues to accelerate with new discoveries and new applications expected to benefit the economy throughout the 21st century.

In its broadest definition, biotechnology is the application of biological techniques and engineered organisms to make products or modify plants and animals to carry desired traits. This definition also extends to the use of various human cells and other body parts to produce desirable products. Bioindustry refers to the cluster of companies that produce engineered biological products and their supporting businesses. Biotechnology refers to the use of the biological sciences (such as gene manipulation), often in combination with other sciences (such as materials sciences, nanotechnology, and computer software), to discover, evaluate and develop products for bioindustry. Biotechnology products have made it easier to detect and diagnose illnesses. Many of these new techniques are easier to use and some, such as pregnancy testing, can even be used at home. More than 400 clinical diagnostic devices using biotechnology products are in use today. The most important are screening techniques to protect the blood supply against contamination by AIDS and the hepatitis B and C viruses.


Biotechnology

I.I. Amarakoon , . M.E. Roye , in Pharmacognosy , 2017

28.17 Review Questions

Define biotechnology ? Has your perception of biotechnology been changed by this definition.

What are some of the products of: a.

Discuss the color code used to differentiate between the different areas of biotechnology.

Discuss some of the applications of biotechnology in medicine and agriculture.

Natural fresh water bodies and the ocean are large untapped sources of biotechnology products. Discuss using specific examples.

What do you understand by the term “recombinant DNA technology”? How is recombinant DNA technology different from hybridoma technology?

Polymerase chain reaction (PCR) and DNA cloning.

DNA hybridization and DNA sequencing.


Biotechnology: Introduction, Scope and Applications of Biotechnology

Read this article to learn about the scope and applications of biotechnology.

The applications of biotechnology includes plant tissue culture, production of transgenic in animal and plants, applications in medicine as tools and therapeutics, creation of new enzymes and their immobilization for industrial use, development of monoclonal antibodies and control of pollutions, etc.

1. Introduction:

Biotechnology is defined as the ‘application of scientific and engineering principles to the processing of material by biological agents to provide goods and services’. The Spinks Report (1980) defined biotechnology as ‘the application of biological organisms, systems or processes to the manufacturing and service industries’. United States Congress’s Office of Technology Assessment defined biotechnology as ‘any technique that used living organisms to make or modify a product, to improve plants or animals or to develop microorganisms for specific uses’.

The document focuses on the development and application of modern biotechnology based on new enabling techniques of recombinant-DNA technology, often referred to as genetic engineering. The history of biotechnology begins with zymotechnology, which commenced with a focus on brewing techniques for beer. By World War I, however, zymotechnology would expand to tackle larger industrial issues, and the potential of industrial fermentation gave rise to biotechnology. The oldest biotechnological processes are found in microbial fermentations, as born out by a Babylonian tablet circa 6000 B.C. unearthed in 1881 and explaining the preparation of beer.

In about 4000 B.C. leavened bread was produced with the aid of yeast. The Sumerians were able to brew as many as twenty types of beer in the third millennium B.C. In the 14th century, first vinegar manufacturing industry was established in France near Orleans.

In 1680 Antony Van Leeuwenhoek first observed yeast cells with his newly designed microscope. In 1857, Louis Pasteur highlighted the lactic acid fermentation by microbe.

By the end of 19th century large number of industries and group of scientists were involved in the field of biotechnology and developed large scale sewage purification system employing microbes were established is Germany and France.

In 1914 to 1916, Delbruck, Heyduck and Hennerberg discovered the large-scale use of yeast in food industry. In the same period, acetone, butanol and glycerin were obtained from bacteria.

In 1920, Alexander Fleming discovered penicillin and large scale manufacturing of penicillin started in 1944. Table 22.1 presents chronological history of biotechnology.

Fermentation to Produce Foods:

Fermentation is perhaps the most ancient biotechnological discovery. Over 10,000 years ago mankind was producing wine, beer, vinegar and bread using microorganisms, primarily yeast. Yogurt was produced by lactic acid bacteria in milk and molds were used to produce cheese. These processes are still in use today for the production of modern foods. However, the cultures that are used have been purified and often genetically refined to maintain the most desirable traits and highest quality of products.

Industrial Fermentation:

In 1897 the discovery that enzymes from yeast can convert sugar to alcohol lead to industrial processes for chemicals such as butanol, acetone and glycerol. Fermentation processes are still in use today in many modern biotech organizations, often for the production of enzymes to be used in pharmaceutical processes, environmental remediation and other industrial processes.

Food Preservation:

Drying, salting and freezing foods to prevent spoilage by microorganisms were practiced long before anyone really understood why they worked or even fully knew what caused the food to spoil in the first place.

Quarantines:

The practice of quarantining to prevent the spread of disease was in place long before the origins of disease were known. However, it demonstrates early acceptance that illness could be passed from an infected individual to another healthy individual, who would then begin to have symptoms of the disease.

Selective Plant Breeding:

Crop improvement, by selecting seeds from the most successful or healthiest plants, to obtain a new crop having the most desirable traits, is a form of early crop technology. Farmers learned that using only the seeds from the best plants would eventually enhance and strengthen the desired traits in subsequent crops. In the mid-1860’s, Gregor Mendel’s studies on inheritable traits of peas improved our understanding of genetic inheritance and lead to practices of cross-breeding (now known as hybridization).

In last fifteen years progress have been made by microbiologists and genetic engineers, and we are hopeful to solve many fold problems of the present day, specially energy and food crisis to cater the need of growing population of the world. Mineral ore deposits are also becoming more scarce and expensive to recover from earth’s crust.

Microorganisms can be used to enhance to recovery of metals from low-grade ores and from effluents containing undesirable quantities of heavy metals or other toxins. When these technologies are applied at industrial level, they constitute bio-industry (Table 22.2).

2. Scope of Biotechnology:

Genetic engineering in biotechnology stimulated hopes for both therapeutic proteins, drugs and biological organisms themselves, such as seeds, pesticides, engineered yeasts, and modified human cells for treating genetic diseases. The field of genetic engineering remains a heated topic of discussion in today’s society with the advent of gene therapy, stem cell research, cloning, and genetically-modified food.

Biotechnology is the applied science and has made advances in two major areas, viz., molecular biology and production of industrially important bio-chemical. The scientists are now diverting themselves toward biotechnological companies this has caused the development of many biotechnological industries.

In USA alone more than 225 companies have been established and successfully working, like Biogen, Cetus, Geneatech, Hybritech, etc. In world, USA, Japan, and many countries of Europe are leaders in biotechnological researchers encouraged by industrialists.

These companies are working for human welfare and opted following areas for research and development:

(a) Automated bio-screening for therapeutic agents.

(b) Bio-processing alkenes to valuable oxides and glycols.

(c) Developing immobilized cell and enzyme systems for chemical process industries.

(d) Engineering of a series of organisms for specific industrial use.

(e) Genetical improvement of microorganisms for production of pharmaceutical products.

(g) Improved production of Vitamin B12.

(h) Large-scale production of fructose from inexpensive forms of glucose.

(i) Manufacturing ethanol by continuous fermentation.

(j) Microbiological based production of human insulin and interferon’s.

(k) Microbiologically up-gradation of hydrocarbons.

(l) Production and development of vaccine to prevent calibacillosis.

(m) Production of bio-pesticide and bio-fertilizers.

(n) Production of diagnostic kits for toxoplasmosis identification.

(o) Production of monoclonal antibodies for organ transplant tissue typing.

(p) Production of photo-synthetically efficient plants.

(q) Production of transgenic plants and animals.

(r) Production of xanthan gum in oil fields for recovery of crude mineral oils.

The advances in recombinant DNA technology have occurred in parallel with the development of genetic processes and biological variations. The development of new technologies have resulted into production of large amount of biochemically-defined proteins of medical significance and created an enormous potential for pharmaceutical industries.

Biotechnology in itself is a vast subject and its scope is extended to various branches of biology. This includes plant tissue culture, production of transgenic in animal and plants, applications in medicine as tools and therapeutics, creation of new enzymes and their immobilization for industrial use, development of monoclonal antibodies and control of pollutions, etc.

3. Applications:

Industrial Applications of Biotechnology:

The industrial application of molecular biotechnology is often subdivided, so that we speak of red, green, gray or white biotechnology. This distinction relates to the use of the technology in the medical field (in human and animal medicine), agriculture, the environment and industry.

Some companies also apply knowledge deriving from molecular biotechnology in areas that cut across these distinctions (e.g., in red and green biotechnology, sequencing services). According to an investigation by Ernst and Young relating to the German biotech industry, 92% of companies are currently (2004) working in the field of red biotechnology, 13% in green, and 13% in gray or white biotechnology.

Biotechnology in Medicine:

Biotechnology products for therapeutic use include a very diverse range of products, as outlined in Tables 22.4, 22.5. Some products are intended to mimic the human counterpart, whereas others are intended to differ from the human counterpart and may be analogues, chemically modified (e.g., pegylated) or novel products (e.g., single chain or fragment antibody products, gene transfer vectors, tissue-engineered products).

Most of these products are regulated as medicinal products however, the regulatory status of others such as some cell therapies and tissue: organ-based products differs globally and falls within the borderline between the practice of medicine, medical devices and medicinal products. Different areas of medicine in which biotechnology is used to develop diagnostic kits and cure are presented in the Figure 22.1.

Biotechnology-derived pharmaceuticals may be derived from a variety of expression systems such as Escherichia coli, yeast, mammalian, insect or plant cells, transgenic animals or other organisms. The expressed protein or gene may have the identical amino acid or nucleotide sequence as the human endogenous form, or may be intentionally different in sequence to confer some technical advantage such as an optimized pharmacokinetic or pharmacodynamics profile.

The glycosylation pattern of protein products is likely to differ from the endogenous human form due to the different glycosylation preferences of the expression system used. Furthermore, intentional post-translation modifications or alterations may be made such as pegylation. It is important for the toxicologist to be aware of the nature of the product to be tested in terms of primary, secondary and tertiary structure, and any post-translational modifications such as glycosylation status, particularly as these may be altered if the manufacturing system is modified.

Red Biotechnology:

Within the field of red biotechnology, which deals with applications in human and animal medicine, there are various further distinctions that can be made: biopharmaceutical drug development, drug delivery cell and gene therapies, tissue engineering/regenerative medicine, pharmacogenomics (personalized medicine), system biology, and diagnosis using molecular medicine.

Biopharmaceutical Drug Development:

In the field of biopharmaceutical drug development, it is the development of therapeutic human proteins by recombinant methods. (Table 22.5) for use as medicines that has the longest tradition. As mentioned above, recombinant human insulin was the first recombinant medicine in the world, produced by Genentech and brought to market in 1982. Today, recombinant human insulin has almost completely driven the other preparation of insulin (isolated from human or animal tissues) from the market.

The first therapeutic antibodies, especially monoclonal antibodies, have been on the market since the late 1990s. In 2002, antibodies were (along with vaccines) the most important therapeutic class of drugs under development and there are also more recent market studies more than 100 antibodies or antibody fragments were at the clinical development stage in 2002 and research and development is being carried out on around 470 more in about 200 companies around the world (Table 22.6,7).

Since the introduction of therapeutic antibodies onto the market, they have achieved significant turnovers, which are growing continually. The market for 2008 is estimated at a volume of US $16.7 billion (from Data-monitor, November 2003). Today, in addition to proteins, which currently play the most significant role in the biopharmaceutical field, new types of drugs based on RNA (antisense drugs, ribozymes, aptamers, Spiegelmers and RNA interference) are also being developed on the basis of advances in knowledge on molecular biotechnology.

Drug Delivery:

Closed linked to the development of therapeutic agents are the means of achieving their targeted delivery to their site of action. These drug delivery systems are mainly used for drugs whose physical and chemical characteristics make them insufficiently stable in reaching their site of action intact. They can also be used to transport drugs in a targeted way to particular sites of action (tissue specific targeting), or to overcome biological barriers such as the intestinal wall or the blood-brain barrier.

Green Biotechnology:

Green biotechnology is the application of biotechnology processes in agriculture and food production. The main dominant forces in green biotechnology today are agro giants with a world­wide area of operation such as BASF, Bayer Crop-Science, Monsanto and Syngenta. They are concentrating considerable attention on molecular plant biotechnology, which is seen as a future growth factor in agro-industry. The traditional pesticide market, on the other hand has been stagnating for years.

Transgenic Plants:

The main emphasis in modern plant biotechnology is the production of transgenic plants. The first use of gene technology to bring about changes in plants became possible at the beginning of the 1980s, around ten years after the first experiment with bacteria. The market value of transgenic plants is estimated to be in excess of 2 billion euros, according to the calculation of the German Federal Office for the Environment. These figures relate to transgenic crop plants, which were being grown on an area totaling about 40 million hectares worldwide in 1999 and 2000.

Novel and Functional food:

New types of foodstuffs with novel properties are often called functional food. Another category that is often mentioned in this context is nutraceuticals. These are foods that have a medicinal effect.

Livestock Breeding:

Modern biotechnology is being employed commercially to introduce novel performance features in productive livestock. The transgenic specimens then display for example different wool characteristics for sheep, or improved milk characteristics in cattle.

Grey/White Biotechnology:

The terms Grey and White Biotechnology have been coined for the application of biotechnological processes in environmental and industrial production contexts. The latter is primarily focused on the production of fine chemicals, in particular technical enzymes.

Technical Enzymes:

Modern biotechnology already dominates the technical enzymes market. They can be found as proteases, lipases, celluloses and amylases for example in modern detergents, where the serve, amongst other purposes as protein and fat solubilizes.

Safety Concerns:

There are a number of safety issues relating to biotechnology products that differ from those raised by low molecular weight products and need to be taken into account when designing the safety evaluation programme for a biotechnology derived pharmaceutical product.

The quality and consistency of the product requires careful control in terms of product identity, potency and purity because of concerns about microbiological safety, impurities arising from the manufacturing process (e.g., host-cell contaminants, endotoxin, residual DNA levels and process chemicals), and the fidelity of the protein sequence and post-translational modifications during process improvements and scale-up.

The immunogenic nature of heterologous proteins, vectors, cells, tissues and process contaminants must also be considered in the design of the safety evaluation programme and appropriate monitoring for anti-product antibodies, particularly neutralizing antibodies included in toxicity studies to aid interpretation of the findings. For gene transfer products, there are concerns about the distribution and persistence of vector sequences, the potential for expression of vector sequences in non-target cells: tissues and, in particular, the potential for inadvertent gonadal distribution and germ-line integration.

In 1997, the Food and Drug Administration (FDA) became aware that preclinical studies from multiple clinical trial applications indicated evidence of vector DNA in animal gonadal tissues following extra gonadal administration. These positive polymerase chain reaction (PCR) signals were for DNA extracts from whole gonads subsequent to vector administration. The observations involved multiple classes of vectors, formulations and routes of administration.


7.23A: Overview of Biotechnology - Biology

Biotech improves crop insect resistance, enhances crop herbicide tolerance and facilitates the use of more environmentally sustainable farming practices. Biotech is helping to feed the world by:

  • Generating higher crop yields with fewer inputs
  • Lowering volumes of agricultural chemicals required by crops-limiting the run-off of these products into the environment
  • Using biotech crops that need fewer applications of pesticides and that allow farmers to reduce tilling farmland
  • Developing crops with enhanced nutrition profiles that solve vitamin and nutrient deficiencies
  • Producing foods free of allergens and toxins such as mycotoxin and
  • Improving food and crop oil content to help improve cardiovascular health.

Currently, there are more than 250 biotechnology health care products and vaccines available to patients, many for previously untreatable diseases. More than 13.3 million farmers around the world use agricultural biotechnology to increase yields, prevent damage from insects and pests and reduce farming's impact on the environment. And more than 50 biorefineries are being built across North America to test and refine technologies to produce biofuels and chemicals from renewable biomass, which can help reduce greenhouse gas emissions.

Recent advances in biotechnology are helping us prepare for and meet society’s most pressing challenges.

BIO is the world's largest trade association representing biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations.

We offer membership, events, industry analysis reports and more that serve the entire spectrum of the biotech industry.

BIO has put together several comprehensive reports and tools for detailed industry analysis on COVID-19 therapeutic developments, emerging company investment trends, chronic disease trends, clinical success rates and more.


Intellectual Property Rights and Biotechnology: An Overview

Read this article to learn about the intellectual property rights of biotechnology. The intellectual property is divided into two categories:

(1) Industrial Property, which includes inventions (patents), trademarks, industrial designs, and geographic indications of source and (2) Copyright, which includes literary and artistic works such as novels, poems and plays, films, musical works, artistic works such as drawings, paintings, photographs and sculptures, and architectural designs.

Introduction:

Intellectual property refers to creations of the mind: inventions, literary and artistic works, and symbols, names, images, and designs used in commerce. Intellectual property is divided into two categories: Industrial property, which includes inventions (patents), trademarks, industrial designs, and geographic indications of source and Copyright, which includes literary and artistic works such as novels, poems and plays, films, musical works, artistic works such as drawings, paintings, photographs and sculptures, and architectural designs.

Rights related to copyright include those of performing artists in their performances, producers of phonograms in their recordings, and those of broadcasters in their radio and television programs. In recent years, instruments enforcing intellectual property rights (IPRs), such as patents and trade secrets, have received attention as mechanisms by which biodiversity resources may be maintained while promoting sustainable development and a more equitable distribution of the resulting benefits among nations.

Most of the world’s biodiversity-rich countries are underdeveloped and lack the necessary technologies to transform biological resources into products yielding significant measurable benefits. With little or insignificant in situ market value, biodiversity-rich wild lands may be expected to succumb to pressure from development activities (e.g., conversion to cropland, inundation of forest lands due to hydroelectric and flood-control projects, etc.).

One way to prevent the destruction of wild lands (and, in turn, biodiversity loss) is to promote biodiversity prospecting which creates new markets for biological resources and generates incentives for their conservation. However, biodiversity prospectors generally are multinational corporations from developed countries. These corporations are reluctant to invest in biotechnologies discovered in developing countries due to poorly defined and enforced intellectual property laws.

Several scientists currently are addressing this deficiency in IPR protection. Nations which have become signatories of two major international agreements in recent years: the 1992 Convention on Biological Diversity (CBD) (UNEP, 1992) and the 1993 Trade-Related Intellectual Property Rights (TRIPS) (UN, 1993). These agreements call for establishing a set of suitable intellectual property laws in each nation, depending on the type of intellectual material in question and the economic and technological background of the nation itself.

CBD establishes a formal framework for the reciprocal transfer of biological resources and knowledge (technology) between nations. The convention promotes the idea of biodiversity as a global common heritage, which, therefore, requires biodiversity-rich countries to allow access to biological resources to other countries on ‘mutually agreed terms’ (UN, 1993). CBD requires technology-rich nations-generally, developed nations to encourage transfer of technology to biodiversity-rich, underdeveloped countries. Thus, the Convention promotes the exchange of biological resources for technology to facilitate biodiversity prospecting, which benefits all nations in the world.

Even though the resource-technology reciprocity and IPR provisions of these agreements have strong economic justification, their use at the global level raises issues concerning the transfer of wealth and respect for national and cultural sovereignty. These issues may become pressing in situations where the resource consumption associated with a patented biotechnology comes in direct conflict with traditional uses of a region’s biological resources.

Conflict may take different forms. First, the developer of a new biotechnology who normally has greater financial strength- might out-compete traditional users for raw biological material in the input market by paying higher prices.

However, the products produced by the new commercial user and traditional users may not compete with each other in the output market. Second, the commercial product developed may have intellectual similarity with traditional products.

Then, conferring IPR to a new product/ technology may limit or prevent traditional consumers from continuing their use of biological resources. Third, the new commercial product may become a substitute for a traditional product and available at a cheaper price. The lower output market price may drive the traditional producers out of business. Such conflicts can alter the underlying market incentives of competing resource users, with likely adverse implications for biodiversity.

Intellectual Property Protection of Plant Biotechnology Inventions:

It is becoming more and more difficult to obtain broad claims in patents and the strength of broad claims in issued patents is weakening. A recent example of this is a case in the USA, in which claims to a diagnostic assay – to differentiate one genus of bacteria from other were invalidated.

Trips:

The standard for intellectual property rights is outlined in the global intellectual property treaty agreement of Trade-Related Aspects of Intellectual Property Rights (TRIPS). Member countries that have signed this agreement must ensure that the requirements stated in TRIPS are met in their own legislation. TRIPS states that ‘patents shall be available for any inventions, whether products or processes, in all fields of technology, provided that they are new, involve an inventive step and are capable of industrial application’.

Although seemingly simple and consistent with the requirements for obtaining a patent in most developed countries, this statement is at the heart of most of the controversy relating to biotechnology patenting. An additional paragraph in TRIPS permits several grounds for exclusion in granting patent protection, including exclusion on moral grounds or diagnostic, therapeutic and surgical methods for the treatment of humans or animals, life forms other than microorganisms and processes for the production of plants or animals. However, these exclusions are optional and vary from country to country.

For example, the European Patent Convention (EPC) provides limited moral grounds for exclusion, yet no such grounds are defined in the Patent Acts in Canada, Australia, the USA or Japan.

TRIPS also state that if protection of plants is not available by patent, then member countries need to provide protection in some other way. A standard method for such alternative protection is plant variety protection, as set out under Union International pour la Protection des Obtentions Vegetables, known more simply as UPOV.

Plant Variety Protection:

UPOV is a global agreement setting out a minimum standard for the protection of plant varieties, similar to that of TRIPS. Member states that have signed the UPOV Convention must ensure that these standards are met within their own legislation (Table 20.1). The two versions of UPOV that are currently in force are set out in the UPOV Conventions of 1978 and 1991 and are similar in that they provide protection to a plant variety that is distinct from existing known varieties and that is uniform, stable and novel.

However, there are several significant changes in the 1991 Act. For example, the definition of propagating material has been tightened and provisions relating to farmers’ rights (or privilege) the rights that permit a farmer to replant seed for personal use have been defined.

Although plant variety protection meeting the standard set out under UPOV is accepted in 50 countries, such protection has not been uniformly accepted and many countries with strong histories of farmers’ privilege have yet to accede to the convention. A rigorous debate also continues over the effect of plant variety protection and associate Material Transfer Agreements, on sharing and developing new germplasm.

UPOV 1978 provides an exclusive right to produce and offer for sale propagating materials of a plant variety but not the harvested end product, for example a fruit. Furthermore, the right pertains only to a commercial end product and not to non-commercial uses. As a result, replanting seed is implicitly allowed under UPOV 1978, leading to farmers’ privilege.

Also provided in the 1978 convention was a breeders’ exemption permitting the use of protected varieties as a germplasm source to develop new plant varieties. The 1991 Act introduced several significant amendments. The number of plant genera and species that could be protected under UPOV was increased from the select list of plants in UPOV 1978 to all plants.

Furthermore, the 1991 Act provides the option to protect all aspects of the production and reproduction of a plant variety, thereby removing farmers’ privilege. However, the application of this provision is discretionary for each member state of UPOV and a country can provide an exemption in its laws to permit farmers’ privilege, if desired. Another important change pertains to providing protection to plant varieties that are ‘essentially derived’ from a protected variety.

An ‘essentially derived’ plant is one that comprises the properties of the protected variety along with only a minor change. The introduction of a gene using recombinant techniques into a protected plant variety might not be sufficient to exceed the ‘essentially derived’ criteria unless the gene alters the variety in a significant manner.

On 3 November 2001, the International Treaty on Plant Genetic Resources was adopted by 116 countries there were two abstentions (the USA and Japan). Before the Treaty comes into effect 40 countries must ratify it. This Treaty pertains to ensuring that the raw materials used to develop new crop varieties remain publicly available.

In so doing, the Treaty promotes the conservation of plant genetic resources for food and agriculture. The aim of the Treaty is to ensure farmers’ privilege and to develop a multilateral system comprising an aggregate of genetic material from the member countries, so that, after paying a fee, members can have access to the genetic material.

The preface to the Treaty indicates that ‘nothing in this Treaty shall be interpreted as implying in any way a change in the rights and obligations of the Contracting Parties under other international agreements’. However, there is an active debate as to whether the Treaty will remain subordinate to TRIPS and UPOV. The USA abstained from signing this treaty partly because of the lack of clarity in the intellectual property provisions.

GATT (General Agreement on Tariffs and Trade):

During Urugway conference, WTO (World Trade Organization) was created. General Agreement on Tariffs and Trade (GATT) was framed by WTO in 1948 and was meant to be a temporary arranged to settle amicably, among countries, disrupts regarding who gets what share of world trade. This is achieved by determining both tariff rates and quantitative restrictions on imports and exports globally. In 1994, about 100 countries signed this agreement including the then president of USA, Mr. Bill Clinton. This was to be effective from 1-1-95 in phases. Its new quarter is in Geneva, Switzerland.

Although GATT has made the world a better place to do business by allowing more free and fruitful flow of goods and services, this benefit has unfortunately gone mainly to developed countries to the disadvantage of the countries in the third world.

US Plant Patents:

Another way to protect plant-related subject matter includes a ‘plant patent’, a unique form of protection offered in the USA. A US plant patent is available for a plant that reproduces through asexual reproduction but it does not include a tuber-propagated plant. Although not a common form of plant protection, it is used to protect ornamental and fruit-producing trees, roses, poinsettias, strawberries and other plants that reproduce asexually. A plant patent is different from a regular utility patent.

In the autumn of 2000, the USPTO (United States Patent and Trademark Office) began rejecting plant patents with a UPOV-based certificate that had been issued before filing for the corresponding plant patent application if the UPOV-based application had been >1 year before the plant patent application had been filed.

This interpretation of a UPOV-based disclosure had not been made previously because it was not considered ‘enabling’, that is, the disclosure of a plant variety within a Plant Breeder Right’s certificate did not provide enough information to enable someone ‘one of skill in the art’ – to produce the plant variety.

The position taken by the USPTO is in direct opposition to that decided in re LeGrice but the USPTO argued that rejection on these grounds is consistent with Ex parte Thomson. However, it should be noted that the only public disclosure made in re LeGrice was a notice in a publication, which is arguably a non-enabling disclosure, whereas in ex parte Thomson, seeds were made publicly available for >1 year before application for a plant patent, clearly placing one of skill in the art in possession of the invention.

The applicant of a US plant patent is provided with a 1 year period of grace. Strong pressure from the industry resulted in a review of USPTO’s position and the issue of a preliminary statement recanting its position and, in May 2002, an amendment to the US Patent Act was proposed (it is still under discussion), providing a 10-year period of grace. Even so, the question as to whether a public, non-enabling disclosure of a plant is sufficient to permit one of skill in the art to be in possession of the invention, as is the case in re LeGrice, was not addressed.

Utility Patents:

Plants can also be protected using a regular (utility) patent in countries that permit patenting of plant or higher life forms (HLFs). This is a more common method for protecting whole novel plants, plant genes, methods for creating novel plants and novel applications for an existing plant.

However, the costs are greater and the process more involved than plant variety protection. Many major jurisdictions permit the patenting of non-human HLFs, including Europe, the USA, Japan and Australia. In the USA, patents have been granted to HLFs since the 1980 landmark decision in Diamond v/s Chakrabarty. The recent Supreme Court decision in the case of Pioneer Hi-Bred International, Inc., v/s J.E.M. AG Supply. Inc. et.al. Further established that such protection is valid for plants, even if protection of a plant is available through either plant variety protection or plant patent protection. This case also confirmed that plants are a composition of matter, as ruled earlier by the US Patent Board of Appeal.

The scope of protection offered by a utility patent is broader than that available under plant variety protection. As noted above, a farmer saving and replanting seed, and a breeder producing a new variety, can do so without infringing a plant variety certificate. However, if a utility patent, the patent owner, protects the plant or licensee has the right to exclude the making, using or selling of the plant or seed, making a user buy seed every year.

Gene Patenting:

Although patents have been granted on nucleotide sequences for >30 years, there has been much recent controversy surrounding the patenting of genes. Genome sequencing initiatives coupled with improved techniques for identifying and sequencing genes, has resulted in an exponential increase in the number of gene patents in the last decade.

As a result, the obscure world of gene patenting is now being scrutinized closely in many different sectors, not least because the effect of these patents is felt in everyday life, especially healthcare. For example, in Europe, a European Parliament resolution regarding the patenting of BRCA 1 and BRCA 2 (breast cancer associated) genes was passed calling on the EPO (European Patent Office) to ensure that all patent applications in Europe do not violate the principle of non-patentability of humans, their genes or cells in their natural environment.

The resolution identified two European patents related to BRCA 1 and BRCA 2 and asked that an official objection be filed against these patents. The importance of intellectual property in India is well established at all levels- statutory, administrative and judicial. India ratified the agreement establishing the World Trade Organisation (WTO). This Agreement, inter-alia, contains an Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS) which came into force from 1st January 1995.

Patenting of Life Forms and GMO:

Life forms such as microorganisms, plants and animals, are not patentable in India under the provisions Indian patent Act (1970). However, patent can be obtained for various biotechnological processes and product applications within the scope of International conventions. In America, Europe and other developed countries, microorganisms isolated from nature or are obtained by simple manipulations are not patentable. But microorganisms obtained by novel techniques like genetic engineering are patentable.

The first patent of GMO (Genetically Modified Organisms) was allowed by US Supreme Court in 1980 as described in utility patent. A maize plant over producing tryptophan amino acid was patented in USA in 1985. This was beginning of patenting of high organisms for patenting. For animals, a patent was granted in 1988 for ‘oncomouse’, genetically modified mouse in USA.

In USA, non-naturally occurring non-human multi-cellular organisms are now considered patentable by US patent and trademark office. This clearly excludes humans and human parts. There is long debate about patenting of life forms including GMO and several organizations and religious groups are opposing the patenting of these life forms.

Copyrights:

India’s copyright law, laid down in the Indian Copyright Act, 1957 as amended by Copyright (Amendment) Act, 1999, fully reflects the Berne Convention on Copyrights, to which India is a party. Additionally, India is party to the Geneva Convention for the Protection of rights of Producers of Phonograms and to the Universal Copyright Convention. India is also an active member of the World Intellectual Property Organisation (WIPO), Geneva and UNESCO.

The copyright law has been amended periodically to keep pace with changing requirements. The recent amendment to the copyright law, which came into force in May 1995, has ushered in comprehensive changes and brought the copyright law in line with the developments in satellite broadcasting, computer software and digital technology. The amended law has made provisions for the first time, to protect performer’s rights as envisaged in the Rome Convention.

Trade Secrets:

Trade secrets often include private proprietary information that allows a definite advantage to the owner. This can be illustrated by the popular example of Coca-Cola brand syrup formula which is not known publically under trade-secret.

Trade secrets in the area of biotechnology may include material like:

(i) Hybridization conditions

(iii) Corporate merchandising plan or

Unlike patents, trade secrets have an unlimited duration and therefore may not be required to satisfy the more difficult conditions laid down for patent applications. Disclosure of a trade secret and its unauthorized use can be punished by the court and the owner may be allowed compensation. However if a trade secret becomes public knowledge by independent discovering or other means, it is no longer protectable.


History of Biotechnology

DURING THE PRE-18TH CENTURY

  • Most of the inventions and developments in these periods are termed as “discoveries” or “developments”. Such inventions were based on common observations about nature, which could be put to test for the betterment of human life at that point in time (Berkeley 2012).
  • During the ancient times, man, in order to meet the basic need for food, explored the possibilities of making food available and accessible by growing them near their shelters.

This then paved the way to another needs like the development of methods for preserving food and its storage.

Man made new observations and invented food products like cheese and curd. In history, the invention of cheese can be considered as one of the first direct products of biotechnology.

The exploitation of yeast in various products like making bread, producing vinegar, and fermenting products was done largely for human benefit. The discovery of yeast also paved the way for the production of alcoholic beverages like wine, whiskey and beer.


Hybridization, Southern Blotting, and Northern Blotting

Nucleic acid samples, such as fragmented genomic DNA and RNA extracts, can be probed for the presence of certain sequences. Short DNA fragments called probes are designed and labeled with radioactive or fluorescent dyes to aid detection. Gel electrophoresis separates the nucleic acid fragments according to their size. The fragments in the gel are then transferred onto a nylon membrane in a procedure called blotting (Figure). The nucleic acid fragments that are bound to the surface of the membrane can then be probed with specific radioactively or fluorescently labeled probe sequences. When DNA is transferred to a nylon membrane, the technique is called Southern blotting , and when RNA is transferred to a nylon membrane, it is called northern blotting . Southern blots are used to detect the presence of certain DNA sequences in a given genome, and northern blots are used to detect gene expression.

Southern blotting is used to find a particular sequence in a sample of DNA. DNA fragments are separated on a gel, transferred to a nylon membrane, and incubated with a DNA probe complementary to the sequence of interest. Northern blotting is similar to Southern blotting, but RNA is run on the gel instead of DNA. In western blotting, proteins are run on a gel and detected using antibodies.


Other Industries: Production of Enzymes, Natural Products and Metabolites

Edible Products

Annual and perennial crops produce a yearly output of >87 million tonnes in traded vegetable oils that is worth about $40–45 billion. Plant-derived oils are mainly used as commodities for the manufacture of foodstuffs. Oil crops are second only to cereals as a source of calories for human societies as well as providing essential fatty acids, such as linoleic acid, plus many of the lipid-soluble vitamins including carotenoids (vitamin A) and tocopherols (vitamin E). Some plant oil-derived foodstuffs such as cooking oils, margarine or chocolate are quite obviously lipidic and are called visible fats. However, the vast majority of the plant oils that are consumed in the western diet are the so-called invisible fats that lurk in over half of all the food products in a typical supermarket. These invisible fats are found in nearly all processed foods including biscuits, shortenings, cakes, breads, canned foods, frozen foods, yogurts, milk substitutes, spreads and dips, to name but a few.

There are two important targets for improving the edible quality of plant oils. First, the amount of C18 polyunsaturates should be reduced substantially. This would avoid the need for chemical hydrogenation, which produces the high levels of trans-fatty acids that many people believe to be undesirable in the diet. The extent of trans-fatty acids in foods may well become more apparent if the US Food and Drug Administration (FDA) proceeds with plans for their mandatory labelling in all food products by 2002 (Anonymous, 2000 ). Secondly, the amount of the very long chain (C20–C24) ω-3 polyunsaturates, such as docosahexenoic acid (DHA) or eicosapentenoic acid (EPA), should be substantially increased. These fatty acids are nutritionally beneficial precursors of hormones and physiological effectors such as prostaglandins, leukotrienes and thromboxanes. Fish and other marine creatures accumulate oils that are rich in DHA and EPA, but in recent years stocks have been drastically depleted by overexploitation, leading to the virtual elimination of some fisheries, such as the North Atlantic cod. It is estimated by the FAO that the shortfall between the annual demand for seafood and its supply from wild fisheries will be 50 million tonnes by 2025: it is most unlikely that fish farms can compensate for this shortfall. The resulting decrease in availability and high prices for marine oils make it necessary to consider alternative sources of these useful fish-derived fatty acids, particularly for less affluent groups in the population.

Margarines enriched in phytosterols extracted from (non-transgenic) wood pulp or vegetable oils have recently been marketed and, despite an appreciable price premium compared to conventional margarines, they have enjoyed modest commercial success. The appeal of the sterol-enriched margarines is based on evidence that they may help in reducing blood cholesterol levels and hence combat heart disease (Moreau et al., 1999 ). Such products could be made more cheaply, if more of the phytosterols were synthesised in the same seeds as the oil from which the margarine is derived, and efforts are under way to upregulate phytosterol biosynthetic pathways in transgenic plants.

Proteins

Interest in manipulating seed protein composition via transgene insertion has largely focussed on objectives such as increasing the levels of essential amino acids, e.g. methionine, and in changing the protein structure to enhance qualities, such as breadmaking ability. Many seed storage proteins are relatively deficient in the sulphur amino acids, methionine and cysteine. These amino acids are required in the human diet because they cannot be synthesised endogenously. There have even been rare cases of children reared on non-dairy vegetarian diets who developed significant deficiency symptoms due to the lack of these essential amino acids. One strategy to increase levels of sulphur amino acids in seeds is to create transgenic plants expressing a new protein that is enriched in these desirable amino acids. This was done by a group at Pioneer who expressed a Brazil nut storage protein in transgenic soybean with a resultant satisfactory increase in the methionine content of the seeds. Unfortunately, subsequent tests showed that some people were allergic to the Brazil nut protein and, therefore, would also probably be allergic to all of the many dozens of the soybean-derived food products in which it could be present. Although this was depicted in the literature at the time as a serious setback for agbiotech, it actually demonstrated that the quality control safeguards were effective since the problem was recognised at an early stage, and further development of these transgenic seeds was halted forthwith. Nevertheless, this episode has served as a salutary warning of the risks of generating allergens, particularly when manipulating seed proteins, which are present in considerable abundance in many staple foodstuffs.

Other Nutritional Modifications

About half of all food products in developed countries are nutritionally enhanced to some degree. Examples include fibre-enriched foods, sugar substitutes, vitamin D milk, low-fat or no-fat meat, yogurt and spreads, fortified vegetables and sterol margarines. The market sector was valued at $58 billion in 2000. It is therefore not surprising that transgenic approaches are currently being used to produce several crops with enhanced nutritional value.

Probably the best-known recent example of a nutritionally enhanced crop is the development of the transgenic ‘golden rice’ by a Swiss-based group (Ye et al., 2000 ). The grains of this rice variety are yellow because of the accumulation of β-carotene (provitamin A), which is normally absent from rice grains. The transgenic rice contains three inserted genes encoding the enzymes responsible for conversion of geranyl geranyl diphosphate to β-carotene. It is claimed that consumption of this rice by at-risk populations may alleviate vitamin A deficiency (leading to night blindness) that currently afflicts some 124 million children worldwide. Such claims are hotly disputed by anti-GM groups (e.g. Greenpeace Server, http://www.greenpeace.org/

geneng/), and the ‘golden rice’ has yet to prove itself in large-scale field and nutritional trials in the target developing countries. Interestingly, the rights for the commercial exploitation of ‘golden rice’ in developed countries have now been acquired by Syngenta. It is possible that in future we could see ‘golden rice’ being marketed as a vitamin-enhanced product, e.g. in breakfast cereals, which may be more acceptable to the public than the current generation of food from input trait modified GM crops.

Efforts are also under way to produce transgenic staple crops, such as rice, that are enriched in iron. Iron-deficiency anaemia is estimated to affect as many as 1.4 billion women, the vast majority in developing countries. Approaches include increasing iron content by expressing ferritin or metallothionein transgenes, or making the existing iron more available for digestion by reducing levels of the iron-sequestering protein, phytase (Goto et al., 1999 ). Three different transgenic approaches have been combined to increase the iron content in rice seeds, although the effect of these changes on the bioavailability of iron remains to be determined (Lucca et al., 2001 ). In parallel with these transgenic approaches, there have been some significant recent advances in the identification of genes involved in determining the levels of both iron and zinc in crops, such as wheat (Frossard et al., 2000 ), as reviewed by Zimmermann and Hurrell ( 2002 ).

Often the nutritional value of plants that are quite rich in essential metals is severely reduced by chelating agents that sequester the metals and render them non-bioavailable. Probably the best-known example of this is spinach, where only 2% of the iron is actually bioavailable due to the presence of oxalates—sadly, a real-life Popeye would not garner much strength from canned spinach! A common metal chelator in food plants is phytic acid, which can also sequester phosphate. The recent identification of low phytic acid mutants of maize (Raboy, 2000 ) has shown that zinc bioavailability could be increased by as much as 78% (Adams et al., 2000 ). In another study of tortillas made from a transgenic low phytic acid maize, the iron bioavailability was 49% greater than in wild-type controls (Mendoza et al., 1998 ). Progress towards the identification of genes regulating micronutrients and vitamins such as iron, zinc and phosphate opens up the possibility of using marker-assisted selection to produce nutritionally enhanced crops by conventional breeding.

The boundary between nutritional and therapeutic effects of some of these edible products is becoming blurred. Indeed, whereas phytosterol-enriched margarines were readily approved for sale in some European countries, they faced more challenges in the USA. In the case of Benecol, in keeping with some of the prominently advertised health claims, the distributor wished to market the margarine as a dietary supplement. However, the FDA ruled that Benecol must be regarded as a basic food, which means the phytosterols would be regarded as food additives that must have further regulatory approval.

Another interesting example of such ‘functional foods’ is some newly developed brassica vegetables. Most vegetables of the brassica family produce isothiocyanates, which have been shown in animal and human cell culture model systems to exert a protective role against certain carcinogens (Tawfig et al., 1995 Zhang et al., 1994 ). Such studies confirmed long-established folk traditions and more recent epidemiological evidence concerning the role of certain fruits and vegetables in cancer protection (Block et al., 1999 London et al., 2000 ). New isothiocyanate-enriched varieties of vegetables such as broccoli have recently been produced by conventional breeding and are marketed as part of a health lifestyle choice. Transgenic approaches to modify isothiocyanates and other nutritionally relevant secondary products are under way, but are unlikely to be pursued commercially in the present anti-GM climate, which particularly affects many of the target consumers of the so-called lifestyle foods.

The increasing interest in the development and promotion of these and other nutritionally enhanced products raises the question of when do we stop considering them as mainstream foods, and instead regard them as supplements such as evening primrose oil or even as therapeutic agents such as taxol®. Indeed, the agbiotech industry is now interested in a new generation of ‘nutraceuticals’, which are foodstuffs that may contain enhanced levels of known or supposed nutrients or even potent therapeutic agents, such as vaccines or antibodies. In a recent survey, 74% of all US consumers were found to use dietary supplements and the market is valued at $14 billion per year. An interesting comment from the director of a pharmaceutical company was that, whereas it can cost $600 million for FDA approval of a drug defined as a pharmaceutical, the procedure for clinical tests on a nutraceutical, i.e. a food product, would only cost $100 000 to $30 million (Fitzpatrick, 2000 ).

Industrial Products

Enzymes

As yet, very few plant-produced animal or microbial proteins have been developed for commercial production. Two of the rare examples of such proteins are avidin and β-glucuronidase (GUS), both produced in transgenic maize. Avidin is used as a biochemical reagent for research and diagnostics, and may also be developed as a biopesticide (Kramer et al., 2000 Burgess et al., 2002 ). Conventionally, avidin has been obtained from chicken egg whites, where the cost of the starting material is $1000/tons, while sufficient transgenic maize to yield the same amount of avidin costs only $20 (Hood et al., 1997 , 1999 ). GUS is a bacterial protein that is widely used in research labs as a marker enzyme that can be detected in highly sensitive cytochemical, spectrophotometric and fluorimetric assays. When expressed in transgenic maize, GUS is claimed to be significantly cheaper than the GUS purified from bacteria. Both avidin and GUS are now produced as recombinant plant proteins and marketed as research biochemicals by Sigma–Aldrich. Success in the commercial production of these two very different animal and bacterial proteins demonstrates the versatility of plants as expression systems for proteins. Avidin is a small, basic, 17 kDa glycosylated eukaryotic protein, whereas GUS is a relatively large, acidic, 68 kDa non-glycosylated bacterial protein, and yet both were correctly processed and folded into biologically active forms when expressed at high levels in plants. Although these two proteins are only produced on a small scale for niche markets, they may be the harbingers of a much more extensive use of plants as vehicles for molecular farming in future.

Oleochemicals

About 20% of the total output of plant oils is used as a feedstock for the production of oleochemicals. Over the past century, plant oil crops were nearly all bred to provide edible products and their fatty acid compositions are therefore quite restricted, being mostly limited to C16 and C18 saturates and unsaturates. There are many desirable changes that could be made to enhance the industrial uses of plant oils, and the use of transgenes to effect such modifications has been an attractive option. Indeed, the current list of transgenic crops approved for general release in the USA includes only two crops with modified seed quality traits, both with altered oil profiles. By changing the chain length and functionality of the fatty acids, it is possible, in principle, to produce oils with carbon chain lengths from C8 to C24, containing anything from 0 to 5 double bonds or other useful chemical functionalities such as hydroxy, epoxy or acetylinic groups. Such oils can be used for the manufacture of products such as adhesives, paints, detergents, lubricants, nylons, cosmetics and pharmaceuticals, to name but a few. Many oil-bearing seeds already produce some of these novel and potentially useful fatty acids, and such plants have been used as sources of genes for transfer into mainstream oil crops in the hope that the latter would accumulate the novel oils.

The first transgenic crop with a modified output trait to be approved for commercial cultivation was a lauric oil (12-carbon) rapeseed variety grown in 1995 (Murphy, 1999 ). At this time there was a perception that the biochemistry of oil formation in seeds was well understood and that, as an inert storage product, its composition could be easily and radically modified without affecting other metabolic or physiological processes in the plant. Indeed, the initial results were encouraging. The insertion of a single thioesterase gene from the California bay tree converted rapeseed from a plant with no lauric acid in its oil to one that contained 40% lauric (Voelker et al., 1992 ). Genes could also be down-regulated to change the oil profile. The insertion of antisense copies of a stearate desaturase gene resulted in transgenic rapeseed plants with ten times the normal levels of stearic acid in their seed oil (Knutzon et al., 1992 ). During the past decade, genes encoding the vast majority of the enzymes involved in specifying the chain length and functionality of plant fatty acids have been isolated. The insertion of these genes was expected to result in the accumulation of moderate to high levels of the corresponding fatty acids. However, the regulation of fatty acyl composition of oils has turned out to be more complex than was first thought. Indeed, very recent findings suggest that our understanding of even the basic pathway of triacylglycerol oil biosynthesis is far from complete, and that there are probably multiple pathways rather than just one (Murphy, 2003 ).

The consequence of these complexities of plant lipid metabolism has been that, despite many impressive achievements in isolating oil-related genes and producing transgenic plants with modified oil compositions, it has not been yet possible to achieve the kind of high levels, i.e. 80–90% of novel fatty acids, that will make their widespread commercial exploitation possible. The lauric-oil variety of rapeseed has been improved from 40% to 60% lauric by the insertion of several additional transgenes (Voelker et al., 1996 ) but remains far from being a commercial success. The availability of many genes involved in fatty acid modification and the good progress in transforming the main oil crop species will certainly encourage further efforts to resolve the challenge of low levels of novel fatty acid production. But even if such efforts are successful, the commercial success of transgenic oil crops will remain problematic. It will be necessary to identify or develop robust markets for their products—simply substituting for petroleum-derived products is unlikely to be economic for several decades at least, if at all. The additional costs of identity preservation preclude the use of transgenic oils such as large-scale commodities in competition with conventional plant oils, even for industrial applications. In summary, transgenic oil crops may have some potential promise for the long-term future but their commercial prospects over the next few years remain uncertain.

Bioplastics

Virtually all of our conventional plastics are made from non-renewable petroleum-derived products, such as adipic acid and vinyl chloride. An alternative is to harness the ability of soil bacteria, such as Ralstonia eutrophus that are able to accumulate up to 80% of their mass in the form of non-toxic biodegradable polymers called polyhydroxyalkanoates (PHAs). The PHAs are made up of β-hydroxyalkanoate subunits that are synthesised from acetyl-CoA via a relatively short pathway involving as few as three enzymes for the most common PHA, polyhydroxybutyrate (Steinbüchel et al., 1998 ). During the 1980s and 1990s, the UK-based company, ICI, developed a fermentation process to produce PHB and other PHAs in transgenic E. coli cultures expressing PHA genes obtained from bacteria such as Ralstonia eutrophus. However, the price of the resulting plastic was ten times greater than that of conventional plastics. Despite the enormous environmental benefits of these biodegradable plastics (they can be composted into soil and degraded completely in a few months), their high cost has rendered them uneconomic for large-scale production. Interestingly, there is a small but lucrative niche market for biodegradable plastics as the framework of artificial tissues. Following their insertion into the body, the PHAs are gradually broken down and the body reassembles the natural tissue in the same shape as the original PHA template. In such a specialised medical application, the price of this kind of PHA product is obviously not as important as for lower-value materials such as plastic toys, pens or bags, i.e. high-value applications tend to relatively be price-elastic, whereas commodities are not.

The cost of PHAs could be considerably reduced if they were produced on an agricultural scale in transgenic crops. This prospect led Monsanto to acquire rights to PHA production from ICI/Zeneca in the mid-1990s, and to transfer the bacterial genes into transgenic rapeseed plants. Providing the PHAs accumulate in the plastids, and not in the cytosol, it is possible to obtain modest yields of the polymer from either leaves or seeds (Valentin et al., 1999 ). A major, and as yet unresolved, technical hurdle is how to extract the polymer from the plant tissue in an efficient and cost-effective manner. Another complexity is that polyhydroxybutyrate, which is the most widespread PHA, is a rather brittle plastic and is not suitable for most applications. The best plastics are co-polymers of polyhydroxybutyrate with other PHAs, such as polyhydroxyvalerate, and the production of such co-polymers in transgenic plants is considerably more difficult than that of single-subunit polymers. In May 2001, these perceived difficulties coupled with its own cash-flow problems prompted Monsanto to sell its transgenic PHA business to Metabolix (Metabolix Server, http://www.metabolix.com/). Metabolix is now involved in a joint venture with the US Department of Energy worth $14.8 million with the aim of producing PHAs in transgenic plants over the next 5 years. There are several other groups attempting to make PHAs in plants (including one in oil palm), and it will be interesting to see whether these environmentally friendly products can indeed be produced as a viable commercial venture.

Starches

There is a great deal of interest in manipulating complex carbohydrates, such as starches, which are the major products of the principal cereal grain crops such as rice, wheat, maize and barley. It is estimated that 19 million tons of starches, worth some $5 billion, are produced annually (Goddijn and Pen, 1995 ). In the EU and USA, as much as 25–30% of the starch production is used for industrial purposes with the remainder being used in foods and beverages. Unlike oils and proteins, starches are indeterminate molecules, being made up of glucose polymers of varying chain lengths and extents of branching that exhibit considerable diversity in their structure and properties. Starch grains in plants contain two principal polysaccharides, amylose and amylopectin. Both polymers are made up of chains of α(1–4)-linked glucose molecules but, whereas in amylose the chains are long and largely unbranched, in amylopectin the chain length is much shorter and they are joined by frequent α(1–6)-linkages. It is the chain length and branching that largely determine the physical properties of extracted starches, e.g. they may be more or less gelatinous constituents of foodstuffs they can be incorporated into non-food products such as packaging materials or even used to make biodegradable plastics. Since different crops contain different types of seed starch, the useful properties present in the starch form of one crop are often not present in other crops. Hence, the EU imports huge amounts of maize starch for many types of food manufacture because the starches produced in its home-grown cereals, such as wheat and barley, do not have the appropriate structure for these applications.

The indeterminate nature of starches renders them more complex, compared with oils and proteins, in terms of their potential for biotech manipulation within the plant. It is possible to effect some drastic changes in starch composition, e.g. amylopectin levels can be reduced to almost zero by expressing an antisense copy of the granule-bound starch synthase gene in potato tubers (Visser et al., 1992 ). However, it is much more difficult to produce a ‘designer starch’ with a predetermined ratio of amylose:amylopectin and, therefore, with predictable physiochemical properties. Many of the key biosynthetic enzymes involved in starch formation have now been characterised and their genes cloned, but such studies have served to emphasise the complexity of this process. This is true not only at the metabolic level but also at the cellular level of assembly of the paracrystalline starch granules within plastids, where additional proteins may be involved in various aspects of the three-dimensional organisation of the granule. These factors make it difficult to predict the consequences, in terms of seed starch composition, of manipulating the expression of biosynthetic enzymes, such as starch synthase or starch branching enzyme in transgenic plants. Efforts are now under way to understand the biosynthetic and physiochemical mechanisms of starch granule formation in model bacterial systems, and until these bear fruit the use of gene transfer to redesign starches in crop plants for specific end uses will remain an essentially empirical endeavour.


17.1 Biotechnology

In this section, you will explore the following questions:

  • What are examples of basic techniques used to manipulate genetic material (DNA and RNA)?
  • What is the difference between molecular and reproductive cloning?
  • What are examples of uses of biotechnology in medicine and agriculture?

Connection for AP ® Courses

Did you eat cereal for breakfast or tomatoes in your dinner salad? Do you know someone who has received gene therapy to treat a disease such as cancer? Should your school, health insurance provider, or employer have access to your genetic profile? Understanding how DNA works has allowed scientists to recombine DNA molecules, clone organisms, and produce mice that glow in the dark. We likely have eaten genetically modified foods and are familiar with how DNA analysis is used to solve crimes. Manipulation of DNA by humans has resulted in bacteria that can protect plants from insect pests and restore ecosystems. Biotechnologies also have been used to produce insulin, hormones, antibiotics, and medicine that dissolve blood clots. Comparative genomics yields new insights into relationships among species, and DNA sequences reveal our personal genetic make-up. However, manipulation of DNA comes with social and ethical responsibilities, raising questions about its appropriate uses.

Nucleic acids can be isolated from cells for analysis by lysing cell membranes and enzymatically destroying all other macromolecules. Fragmented or whole chromosomes can be separated on the basis of size (base pair length) by gel electrophoresis. Short sequences of DNA or RNA can be amplified using the polymerase chain reaction (PCR). Recombinant DNA technology can combine DNA from different sources using bacterial plasmids or viruses as vectors to carry foreign genes into host cells, resulting in genetically modified organisms (GMOs). Transgenic bacteria, agricultural plants such as corn and rice, and farm animals produce protein products such as hormones and vaccines that benefit humans. (It is important to remind ourselves that recombinant technology is possible because the genetic code is universal, and the processes of transcription and translation are fundamentally the same in all organisms.) Cloning produces genetically identical copies of DNA, cells, or even entire organisms (reproductive cloning). Genetic testing identifies disease-causing genes, and gene therapy can be used to treat or cure an inheritable disease. However, questions emerge from these technologies including the safety of GMOs and privacy issues.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 3 of the AP ® Biology Curriculum Framework. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP ® Biology course, an inquiry-based laboratory experience, instructional activities, and AP ® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices.

Big Idea 3 Living systems store, retrieve, transmit and respond to information essential to life processes.
Enduring Understanding 3.A Heritable information provides for continuity of life.
Essential Knowledge 3.A.1 DNA, and in some cases RNA, is the primary source of heritable information.
Science Practice 6.4 The student can make claims and predictions about natural phenomena based on scientific theories and models.
Learning Objective 3.5 The student can justify the claim that humans can manipulate heritable information by identifying an example of a commonly used technology.
Big Idea 3 Living systems store, retrieve, transmit and respond to information essential to life processes.
Enduring Understanding 3.C The processing of genetic information is imperfect and is a source of genetic variation.
Essential Knowledge 3.C.1 Changes in genotype can result in changes in phenotype.
Science Practice 7.2 The student can connect concepts in and across domain(s) to generalize or extrapolate in and/or across enduring understandings and/or big ideas.
Learning Objective 3.24 The student is able to predict how a change in genotype, when expressed as a phenotype, provides a variation that can be subject to natural selection.

The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards:
[APLO 3.13][APLO 3.23][APLO 3.28][APLO 3.24][APLO 1.11][APLO 3.5][APLO 4.2][APLO 4.8]

Teacher Support

Begin the discussion with the ethical considerations, such as genetic modified foods, the availability of a genome to the government or insurance provider, or modifying a genome for therapy or the sex selection with embryos. These topics will be in the minds of students, so get them out in front and then get into the mechanics of the topic.

Basic Techniques to Manipulate Genetic Material (DNA and RNA)

  • Go through the process of DNA extraction in class as a demonstration. This would probably be the first time the students would have an opportunity to actually see DNA. Bring in a gel from gel electrophoresis and the results of Southern Blotting as illustrations of the techniques. This will help the discussion be a little more concrete.
  • Be sure that students understand the different uses of the word clone, such as molecular cloning, cellular cloning, reproductive cloning. Emphasize that the word is neutral and does not automatically infer a negative process. Earlier discussions of the ethics of the subject should help to put it into context.

Biotechnology is the use of biological agents for technological advancement. Biotechnology was used for breeding livestock and crops long before the scientific basis of these techniques was understood. Since the discovery of the structure of DNA in 1953, the field of biotechnology has grown rapidly through both academic research and private companies. The primary applications of this technology are in medicine (production of vaccines and antibiotics) and agriculture (genetic modification of crops, such as to increase yields). Biotechnology also has many industrial applications, such as fermentation, the treatment of oil spills, and the production of biofuels.

Basic Techniques to Manipulate Genetic Material (DNA and RNA)

To understand the basic techniques used to work with nucleic acids, remember that nucleic acids are macromolecules made of nucleotides (a sugar, a phosphate, and a nitrogenous base) linked by phosphodiester bonds. The phosphate groups on these molecules each have a net negative charge. An entire set of DNA molecules in the nucleus is called the genome. DNA has two complementary strands linked by hydrogen bonds between the paired bases. The two strands can be separated by exposure to high temperatures (DNA denaturation) and can be reannealed by cooling. The DNA can be replicated by the DNA polymerase enzyme. Unlike DNA, which is located in the nucleus of eukaryotic cells, RNA molecules leave the nucleus. The most common type of RNA that is analyzed is the messenger RNA (mRNA) because it represents the protein-coding genes that are actively expressed. However, RNA molecules present some other challenges to analysis, as they are often less stable than DNA.

DNA and RNA Extraction

To study or manipulate nucleic acids, the DNA or RNA must first be isolated or extracted from the cells. Various techniques are used to extract different types of DNA (Figure 17.2). Most nucleic acid extraction techniques involve steps to break open the cell and use enzymatic reactions to destroy all macromolecules that are not desired (such as degradation of unwanted molecules and separation from the DNA sample). Cells are broken using a lysis buffer (a solution which is mostly a detergent) lysis means “to split.” These enzymes break apart lipid molecules in the cell membranes and nuclear membranes. Macromolecules are inactivated using enzymes such as proteases that break down proteins, and ribonucleases (RNAses) that break down RNA. The DNA is then precipitated using alcohol. Human genomic DNA is usually visible as a gelatinous, white mass. The DNA samples can be stored frozen at –80°C for several years.

RNA analysis is performed to study gene expression patterns in cells. RNA is naturally very unstable because RNAses are commonly present in nature and very difficult to inactivate. Similar to DNA, RNA extraction involves the use of various buffers and enzymes to inactivate macromolecules and preserve the RNA.

Gel Electrophoresis

Because nucleic acids are negatively charged ions at neutral or basic pH in an aqueous environment, they can be mobilized by an electric field. Gel electrophoresis is a technique used to separate molecules on the basis of size, using this charge. The nucleic acids can be separated as whole chromosomes or fragments. The nucleic acids are loaded into a slot near the negative electrode of a semisolid, porous gel matrix and pulled toward the positive electrode at the opposite end of the gel. Smaller molecules move through the pores in the gel faster than larger molecules this difference in the rate of migration separates the fragments on the basis of size. There are molecular weight standard samples that can be run alongside the molecules to provide a size comparison. Nucleic acids in a gel matrix can be observed using various fluorescent or colored dyes. Distinct nucleic acid fragments appear as bands at specific distances from the top of the gel (the negative electrode end) on the basis of their size (Figure 17.3). A mixture of genomic DNA fragments of varying sizes appear as a long smear, whereas uncut genomic DNA is usually too large to run through the gel and forms a single large band at the top of the gel.

Amplification of Nucleic Acid Fragments by Polymerase Chain Reaction

Although genomic DNA is visible to the naked eye when it is extracted in bulk, DNA analysis often requires focusing on one or more specific regions of the genome. Polymerase chain reaction (PCR) is a technique used to amplify specific regions of DNA for further analysis (Figure 17.4). PCR is used for many purposes in laboratories, such as the cloning of gene fragments to analyze genetic diseases, identification of contaminant foreign DNA in a sample, and the amplification of DNA for sequencing. More practical applications include the detection of genetic diseases.

DNA fragments can also be amplified from an RNA template in a process called reverse transcriptase PCR (RT-PCR) . The first step is to recreate the original DNA template strand (called cDNA) by applying DNA nucleotides to the mRNA. This process is called reverse transcription. This requires the presence of an enzyme called reverse transcriptase. After the cDNA is made, regular PCR can be used to amplify it.

Link to Learning

Deepen your understanding of the polymerase chain reaction by clicking through this interactive exercise.

  1. The process of PCR can isolate a particular piece of DNA for copying, which allows scientists to copy millions of strands of DNA in a short amount of time.
  2. The process of PCR can purify a particular piece of DNA, and very small amounts of DNA can be used for purification.
  3. The process of PCR separates and analyzes DNA and its fragments, which requires very little DNA.
  4. The process of PCR anneals DNA molecules to complementary DNA strands, which maintains the same amount of DNA.

Hybridization, Southern Blotting, and Northern Blotting

Nucleic acid samples, such as fragmented genomic DNA and RNA extracts, can be probed for the presence of certain sequences. Short DNA fragments called probes are designed and labeled with radioactive or fluorescent dyes to aid detection. Gel electrophoresis separates the nucleic acid fragments according to their size. The fragments in the gel are then transferred onto a nylon membrane in a procedure called blotting (Figure 17.5). The nucleic acid fragments that are bound to the surface of the membrane can then be probed with specific radioactively or fluorescently labeled probe sequences. When DNA is transferred to a nylon membrane, the technique is called Southern blotting , and when RNA is transferred to a nylon membrane, it is called northern blotting . Southern blots are used to detect the presence of certain DNA sequences in a given genome, and northern blots are used to detect gene expression.

Molecular Cloning

In general, the word “cloning” means the creation of a perfect replica however, in biology, the re-creation of a whole organism is referred to as “reproductive cloning.” Long before attempts were made to clone an entire organism, researchers learned how to reproduce desired regions or fragments of the genome, a process that is referred to as molecular cloning.

Cloning small fragments of the genome allows for the manipulation and study of specific genes (and their protein products), or noncoding regions in isolation. A plasmid (also called a vector) is a small circular DNA molecule that replicates independently of the chromosomal DNA. In cloning, the plasmid molecules can be used to provide a "folder" in which to insert a desired DNA fragment. Plasmids are usually introduced into a bacterial host for proliferation. In the bacterial context, the fragment of DNA from the human genome (or the genome of another organism that is being studied) is referred to as foreign DNA , or a transgene, to differentiate it from the DNA of the bacterium, which is called the host DNA .

Plasmids occur naturally in bacterial populations (such as Escherichia coli) and have genes that can contribute favorable traits to the organism, such as antibiotic resistance (the ability to be unaffected by antibiotics). Plasmids have been repurposed and engineered as vectors for molecular cloning and the large-scale production of important reagents, such as insulin and human growth hormone. An important feature of plasmid vectors is the ease with which a foreign DNA fragment can be introduced via the multiple cloning site (MCS) . The MCS is a short DNA sequence containing multiple sites that can be cut with different commonly available restriction endonucleases. Restriction endonucleases recognize specific DNA sequences and cut them in a predictable manner they are naturally produced by bacteria as a defense mechanism against foreign DNA. Many restriction endonucleases make staggered cuts in the two strands of DNA, such that the cut ends have a 2- or 4-base single-stranded overhang. Because these overhangs are capable of annealing with complementary overhangs, these are called “sticky ends.” Addition of an enzyme called DNA ligase permanently joins the DNA fragments via phosphodiester bonds. In this way, any DNA fragment generated by restriction endonuclease cleavage can be spliced between the two ends of a plasmid DNA that has been cut with the same restriction endonuclease (Figure 17.6).

Recombinant DNA Molecules

Plasmids with foreign DNA inserted into them are called recombinant DNA molecules because they are created artificially and do not occur in nature. They are also called chimeric molecules because the origin of different parts of the molecules can be traced back to different species of biological organisms or even to chemical synthesis. Proteins that are expressed from recombinant DNA molecules are called recombinant proteins . Not all recombinant plasmids are capable of expressing genes. The recombinant DNA may need to be moved into a different vector (or host) that is better designed for gene expression. Plasmids may also be engineered to express proteins only when stimulated by certain environmental factors, so that scientists can control the expression of the recombinant proteins.


7.23A: Overview of Biotechnology - Biology

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Careers

Graduates in Biology with Biotechnology will possess a wealth of skills and knowledge that will be relevant to many employment sectors including hospital laboratories, research organisations, multidisciplinary consultancies, industrial companies, research charities, government departments and agencies, educational establishments, research councils and the private sector.

Opportunities at Bangor

The University’s Skills and Employability Service provides a wide range of resources to help you achieve your graduate ambitions.

The Bangor Employability Award (BEA)

With the BEA, you can gain recognition for your extra-curricular activities (e.g. volunteering, clubs and societies, part-time work, etc.)

Internships

Bangor University runs a paid internship scheme within the university’s academic and service departments.

Student Volunteering

Volunteering widens your experience and improves your employability. Find out more about the volunteering on the Students’ Union’s website.