The virus

Varicella-zoster virus is a double-stranded DNA virus and a member of the Herpesviridae family of viruses.

Epidemiology

Route of spread

Varicella-zoster virus is transmitted by the airborne route, from respiratory secretions and from vesicles on the skin. After entry through the respiratory route there is an initial period of viraemia, which seeds the virus in the reticulo-endothelial system. This is followed by a second episode of viraemia resulting in dissemination of the virus throughout the body and manifestations of the typical chickenpox vesicular rash on the skin surface.

Prevalence

Varicella-zoster virus infection occurs worldwide and the prevalence of infection varies considerably. While 95% of people in industrialized countries have had chickenpox by the age of 20 years (although about 20% will have had such a mild infection that they may be unaware of this), in the tropics, only 50% of people have had chickenpox by the age of 20 years.

Incubation period

10–23 days (mean 14 days).

Infectious period

From 2 days before the onset of symptoms until 5 days after the rash or all the skin lesions are fully crusted.

At-risk groups

• Immunocompromised persons

• Pregnant women

• Unborn babies in the first 20 weeks of pregnancy, and babies one week before or after delivery.

Introduction

Globally, agriculture and food production are committed to produce, in a sustainable way, sufficient, healthful and safe food for the world population. Demographers, who had been until quite recently forecasting a steady exponential rise in world population, have now had to make a major re- adjustment and now estimate world population peaking at c. 10 billion (ten giga people) by 2050–60. World population growth, in percentage terms, had almost stopped by the 1960s and started to decrease by the 1970s. World population is still growing but adding smaller numbers each year. In many parts of the developing world, child births have decreased by up to 50% by greater awareness of the necessity of using modern methods of birth control. To successfully feed 10 billion people will require 35% more calories than presently produced by world agriculture and, indeed, much more, if any increasing proportion of the 10 billion will want to eat meat more than once a month.

To feed this world population there will need to be substantial increases in the production of the staple food commodities: cereals (40%), meat (63%) (it takes ten calories of wheat to produce one calorie of meat) and roots and tubers (40%). At least 80% of this food will need to be produced in developing countries, yet only about 6% of new virgin soil can be brought into cultivation.

Introduction

In essence, all properties of organisms depend on the sum of their genes. There are two broad categories of genes – structural and regulatory. Structural genes encode for amino acid sequences of proteins, which, as enzymes, determine the biochemical capabilities of the organism by catalysing particular synthetic or catabolic reactions or, alternatively, play more static roles as components of cellular structures. In contrast, the regulatory genes control the expression of the structural genes by determining the rate of production of their protein products in response to intra- or extracellular signals. The derivation of these principles has been achieved using well known genetic techniques, which will not be considered further here.

The seminal studies of Watson and Crick and others in the early 1950s led to the construction of the double-helix model depicting the molecular structure of DNA, and subsequent hypotheses on its implications for the understanding of gene replication. Since then there has been a spectacular unravelling of the complex interactions required to express the coded chemical information of the DNA molecule into cellular and organismal expression. Changes in the DNA molecule making up the genetic complement of an organism are the means by which organisms evolve and adapt themselves to new environments. The precise role of DNA is to act as a reservoir of genetic information.

The nature of enzymes

Enzymes are complex globular proteins present in living cells where they act as catalysts that facilitate chemical changes in substances. In 1878 Kühne introduced the term ‘enzyme’ from the Greek enzumos, which refers to the leavening of bread by yeast. With the development of the science of biochemistry has come a fuller understanding of the wide range of enzymes present in living cells and of their modes of action. Without enzymes there can be no life. Although enzymes are only formed in living cells, many can be extracted or separated from the cells and can continue to function in vitro. This unique ability of enzymes to perform their specific chemical transformations in isolation has led to an ever-increasing use of enzymes in industrial and food processes, bioremediation and in medicine, and their production is collectively termed enzyme technology.

The activity of an enzyme is due to its catalytic nature. An enzyme carries out its activity without being consumed in the reaction, while the reaction occurs at a very much higher rate when the enzyme is present. Enzymes are highly specific and function only on designated types of compounds, the substrates. A minute amount of enzyme can react with a large amount of substrate. The catalytic function of the enzyme is due not only to its primary molecular structure but also to the intricate folding configuration of the whole enzyme molecule.

Introduction

The manner in which the public perceive any new technology, including biotechnology, will have important influences on the timing and direction of innovation, and in the rate of uptake or degree of discrimination against the technology, its products and services. Public perception will also be influenced by geographical location, which will reflect several variables, for example, economic affluence, level of education, cultural and religious values and tradition, together with social and institutional ways of participation.

In the industrialised world public policy-makers on biotechnology have been influenced by the concerted interests of governments, industries, academia and environmental groups. Nationally and internationally such policies are being developed within a climate of tension and conflicting aims.

At the early stages of recombinant DNA research, a small group of well recognised molecular biologists met in the early 1970s to express their concern over the safety of this new technology. In a well publicised meeting, the famous (or infamous) Asilomar Conference, in California, they focused on the potential, but highly speculative, risks associated with recombinant DNA (rDNA) technology and how they should be managed. Unfortunately, this generated huge public concern arising from the alarmist media coverage, e.g. Frankenstein foods, Andromeda strains, etc. Following on from this conference and the continued huge media hype, the National Institute of Health (NIH) in the USA published Guidelines for Research Involving Recombinant DNA Molecules, which sent out a powerful message to the scientific community and federal government departments that the NIH were seriously concerned about the speculative risk scenarios.

Biotechnology is increasingly being viewed as a Promethean science, because in so many ways it is transforming the relationship between humans and the planet.

Biotechnology has been shown to be a spectrum of enabling technologies, which are increasingly being applied in many aspects of modern society. The applied use of biological systems, especially microorganisms, in such processes as brewing, wine making and cheese production was primarily accomplished in an empirical manner with the management of these processes seen more as an art rather than a science. In recent times, these ancient biotechnological processes have been subjected to rigorous scientific study and analysis, which has largely led to the replacement of traditional empiricism. Better understanding of microbial strain selection, molecular biology and genetics, together with improved bioprocess technology, have yielded major advances in all of the traditional biotechnology industries and will continue to achieve improved quality and safety together with cost effectiveness.

A central feature of new biotechnological advances derives from an increasing understanding of the mechanisms of life and how these will eventually transform human lives, as well as giving a deeper appreciation of agriculture, aquaculture, forestry and the biological environment. The ability to select and manipulate genetic material within and outside species has permitted unprecedented opportunities to alter life forms for the benefit of society. The successful sequencing of the human and other genomes is the beginning of a new scientific period of discovery.

Introduction

As societies throughout the world are increasingly moving to greater levels of urbanisation and industrial development, public concern is mounting over the state of the environment and much attention is now being given to improving the environment for future generations. To achieve this, there has been, particularly in developed nations, major environmental legislation directed towards liquid, solid and hazardous wastes. In most developing countries, the situation is less encouraging where financing is limited, or not available, for the construction of water and waste treatment facilities and there is a shortage of trained personnel to operate the systems. Furthermore, in many developing countries, there is a lack of official regulations and control systems, no administration bodies responsible for waste control and little obligation for existing and emerging industries to dispose of waste properly. Also it is in such countries that there is the greatest movement towards urbanisation and new industrial development with concomitant destruction of the environment.

Waste generation is a side-effect of consumption and production activities and tends to rise with the level of economic advance. Wastes arise from domestic and industrial activity, e.g. sewage, waste waters, agriculture and food wastes from processing, wood wastes and an ever-increasing range of toxic industrial chemical products and by-products. In the final assessment, wastes represent the end of the technical and economic life of products.

Introduction

Animal agriculture in the form of cattle, pig, sheep, poultry and fish farming represents a major aspect of food production worldwide. While many of these animals are produced for their meat alone, others contribute to human nutrition by way of milk and egg production, and yet others produce products such as wool and leather. In the developed world animal production is highly intensified and technologically driven. Animal production will reflect quality of feed, availability and need of growth hormones, pesticides, antibiotics and vaccines, good animal husbandry and welfare, and increasingly selective breeding, molecular biology, embryo manipulation and gene transfer.

As with plant agriculture early animal breeders sought to identify worthwhile properties in animals and to perpetuate them into future offspring. Selective breeding aims to increase the frequency of a large number of genes that work together with the remainder of the animal's genes or genome to produce the desired phenotype (selective breeding pre-dates our understanding of genes and the science of genetics). Between 1945 and 1993, selective breeding increased milk production of the average dairy cow by a factor of three. Further, when we consider the huge variety of dogs it should be remembered that they are all one species, capable of easily interbreeding, and the present varieties have arisen by carefully controlled selective breeding programmes. For many farm animals conventional breeding has already achieved high-producing animals, but it is apparent that the increases in productivity possible by this means now seem to be approaching a plateau.

A Biomass strategy

It has been estimated that the annual net yield of plant biomass arising from photosynthesis is at least 120 billion tonnes of dry matter on land and around 50 billion tonnes from the world's oceans. Of the land-produced biomass, approximately 50% occurs in the complex form of lignocellulose.

The highest proportion of land-based biomass (44%) is produced as forest (Table 2.1). It is surprising to note that while agricultural crops account for only 6% of the primary photosynthetic productivity, from this amount is derived a major portion of food for humans and animals as well as many essential structural materials, textiles and paper products (Table 2.2). Many traditional agricultural products may well be further exploited with the increasing awareness of biotechnology. In particular, new technological approaches will undoubtedly be able to utilise the large volume of waste material from conventional food processing that presently finds little use.

Biomass agriculture, aquaculture and forestry may hold great economic potential for many national economies particularly in tropical and subtropical regions (Fig. 2.1). Indeed, the development of biotechnological processes in developing areas where plant growth excels could well bring about a change in the balance of economic power.

It should be noted that the non-renewable energy and petrochemical feedstocks on which modern society is so dependent (oil, gas and coal) were derived from ancient types of biomass.

A defining aim of this fifth edition of Biotechnology has been to re-establish the correct understanding of the true meaning of biotechnology.

Biotechnology is in essence the deciphering and use of biological knowledge. It is highly multidisciplinary since it has its foundations in many disciplines including biology, microbiology, biochemistry, molecular biology, genetics, chemistry and chemical and process engineering. It may also be viewed as a series of enabling technologies that involve the practical application of organisms (especially microorganisms) or their cellular components to manufacturing and service industries and environmental management. Historically, biotechnology was an artisanal skill rather than a science, exemplified in the manufacture of wines, beers, cheeses, etc. where the techniques of manufacture were well worked out and reproducible, while the biological mechanisms were not understood. As the scientific basis of these biotechnology processes has developed this has led to more efficient manufacturing of the traditional processes that still represent the major financial returns of biotechnology, i.e. bread, beers, wines, cheeses, etc. Modern biotechnological processes have generated a wide range of new and novel products including antibiotics, vaccines and monoclonal antibodies, the production of which has been optimised by improved fermentation practices. Biotechnology has been further revolutionised by a range of new molecular biology innovations, allowing unprecedented molecular changes to be made to living organisms. The increasing understanding of genomics and proteomics has led to the creation of a vast range of transgenic microorganisms, agricultural (genetically modified) crops and animals, and major new recombinant protein drugs, and has revolutionised activities in the traditional food and drinks industries.

Introduction

In previous chapters the many applications of biotechnology can be divided into the traditional domains of fermentation for the production of various potable beverages, bread, cheese, organic acids, antibiotics and waste treatment, and the new biotechnologies. The new biotechnologies include production and use of genetically modified organisms for the large-scale production of vaccines and therapeutic proteins; their use in plant and animal agriculture and in environmental clean-up; the use of hybridomas for the production of monoclonal antibodies for diagnostic and therapeutic end-points; and, of course, the controversial embryonic stem cells. As such, biotechnology spans a vast range of activities, and considerations of biosafety can potentially encompass activities within the research laboratory, the process plant, the final product and in many cases the environment. The term ‘biosafety’ has evolved as a new area of corporate activity created as an inevitable response generated by an expanding biotechnology industry and its increasing influence upon many aspects of commercial and public life. In particular, the many public issues recently generated, especially in Europe, concerning genetically modified (GM) crop trials has done much to raise the profile of this subject.

In all biotechnology processes, however, safety is of paramount importance. Table 14.1 lists the main areas of consideration for safety aspects of biotechnology.

Concepts of hazard and risk

Essential to the understanding of biosafety is the recognition and appreciation of the terms ‘hazard’ and ‘risk’.

Introduction

During the twentieth century there have been the greatest gains in health in most parts of the world due to dramatic reductions in infant mortality, eradication of life-threatening diseases, such as smallpox, and considerable improvements in life expectancy in developing and industrialised countries. In the past, life for most people was coarse, lacking in adequate nutrition, poor housing and, above all, short in years. With the advent of improved sanitation and better living conditions, together with the availability of vaccinations and antibiotics, there has been, for many, a vast improvement in health status. However, health status still differs widely among nations and by geographical region. For instance, life expectancy is less than 50 years in some sub-Saharan African countries but over 75 in established industrialised countries. The wealthiest economies appear to be the healthiest. A crucial factor related to life expectancy is access to safe water! In much of the developing world, simply drinking water is a high-risk exposure.

Undoubtedly, the real gains in health over the last century can be attributed mainly to the impact of public health and disease prevention rather than to medical interventions. Public health can be primarily distinguished from clinical medicine by placing emphasis on the prevention of disease rather than the curing, and having a main focus on populations and communities rather than the individual patient. It is essential to continue to develop a public health approach that will protect populations and create prevention strategies for groups and not just for individuals.

Introduction

In the present climate of increasing globalisation, biotech companies must seek to acquire strong protection for their products and technologies in all the areas of the world where they wish to operate. It has been projected that the sales worldwide from new biotechnology alone could exceed £60 billion per annum by early this century. This will be derived from a wide range of biotechnology-based products and processes, which have evolved in most cases from many years of expensive research and development. How can such biotechnology products and processes, often referred to as intellectual property (IP), be protected and the due financial profits returned to the rightful inventors and industrial developers? Inventors in the area of biotechnology can be protected by way of different titles of protection including patents for invention, plant breeders' rights and trade secrets.

Intellectual property rights are designed to allow new technologies to be available, so that the originating scientist or company receives a reward for the initiative demonstrated. Intellectual property assets can be any codified knowledge, innovation or anything of actual or potential economic value that has arisen from basic research, analysis and manipulation of biological systems, biological property, industrial application or commercial use.

It is important to differentiate between invention and innovation. Because an invention may not always involve the commercialisation of a new idea, it follows that not all inventions result in innovation.

Introduction

Bioprocess or fermentation technology is an important component of most ‘old’ and ‘new’ biotechnology processes and will normally involve complete living cells (microbe, mammalian or plant), organelles or enzymes as the biocatalyst, and will aim to bring about specific chemical and/or physical changes in biochemical materials derived from the medium. In order to be viable in any specific industrial context, bioprocessing must possess advantages over competing methods of production such as chemical technology. In practice, many bioprocessing techniques will be used industrially because they are the only practical way in which a specific product can be made (e.g. vaccines, antibiotics). Biochemical engineering covers the design of vessels and apparatus suitable for performing such biochemical reactions or transformations.

The very beginnings of fermentation technology, or as it is now better recognised, bioprocess technology, were derived in part from the use of microorganisms for the production of foods such as cheeses, yoghurts, sauerkraut, fermented pickles and sausages, soya sauce and other Oriental products, and beverages such as beers, wines and derived spirits (Table 4.1). In many cases, the present-day production processes for such products are still remarkably similar. These forms of bioprocessing were long viewed as arts or crafts, but are now increasingly subjected to the full array of modern science and technology. Paralleling these useful product formations was the identification of the roles microorganisms could play in removing obnoxious and unhealthful wastes, which has resulted in the worldwide service industries involved in water purification, effluent treatment and solid waste management.

Introduction

A major challenge to creating a sustainable future for the world's populations will be to secure adequate food supplies for the majority. By 2030 it has been estimated that the size of urban populations will be at least twice that of rural, agricultural-based populations. The growth of urbanisation, together with ensuing environmental degradation, is already causing serious losses in the availability of productive agricultural land. Furthermore, worldwide climate changes and increasing civil strife continue to make accurate predictions of future food supplies difficult. What role can traditional and new biotechnology play in achieving food sustainability?

Food production is the largest worldwide industry, and in industrialised nations the expenditure on food can account for at least 20–30% of household budgets. However, whereas food is in general in excessive production in most parts of the world, scarcity and insufficient production exists in Africa, Central China and most parts of South America. The food industry has evolved through specialist trades or occupations, e.g. butchers, bakers, confectioners, etc., to national and multinational organisations involved in the manufacture and distribution of food on a worldwide scale. With the improvement in means of transportation, foods are available on a worldwide basis, and developments in food preservation methods give independence from seasonal availability.

In essence, the food industry now serves the function of supplying society with high-quality, wholesome foods, all the year round, and at a distance, in time and location, from the place of primary production.

Introduction

Major events in human history have, to a large extent, been driven by technology. Improved awareness of agriculture and metalworking brought mankind out of the Stone Age, while in the nineteenth century the Industrial Revolution created a multitude of machinery together with increasingly larger cities. The twentieth century was undoubtedly the age of chemistry and physics, spawning huge industrial activities such as petrochemicals, pharmaceuticals, fertilisers, the atom bomb, transmitters, the laser and microchips. However, there can be little doubt that the huge understanding of the fundamentals of life processes achieved in the latter part of the twentieth century will ensure that the twenty-first century will be dominated by biology and its associated technologies.

Societal changes are increasingly driven by science and technology. Currently, the impact of new biological developments must be absorbed not just by a minority (the scientists) but by large numbers of people (the general public). If this does not happen, the majority will be alienated. It is increasingly important to ensure a broad understanding of what bioscience and its related technologies will involve, and especially what the consequences will be of accepting or rejecting the new technical innovations.

The following chapters will examine how the new biotechnologists are developing new therapies and cures for many human and animal diseases; designing diagnostic tests for increasing disease prevention and pollution control; improving many aspects of plant and animal agriculture and food production; cleaning-up and improving the environment; designing clean industrial manufacturing processes; exploring the potential for biological fuel generation; and unravelling the power of stem cell technology.