Early developments

History. The origins of what we call biotechnology today probably originated with agriculture and can be traced back to early history. Presumably, since the beginning people have gained experience on the loss of food by microbial spoilage; on food conservation by drying, salting, and sugaring; and on the effects of fermented alcoholic beverages. As the first city cultures developed, we find documents and drawings on the preparation of bread, beer, wine, and cheese and on the tanning of hides using principles of biotechnology. In Asia, fermented products such as Sauerkraut (China), Kimchi (Korea) or Gari (Indonesia) have been produced for thousands of years. In Europe, starting in the 6^th century, the monasteries with their well organized infrastructure developed protocols for the arts of brewing, wine-making, and baking. We owe our strong, alcohol-rich stout beers to the pious understanding of the monks that “Liquida non fragunt ieiunum” (Liquors do not interfere with the chamfering time). Modern biotechnology, however, is a child of microbiology, which developed significantly in the late 19^th century. The First and Second World Wars in the first half of the 20^th century next probably provided the strongest challenge to microbiologists, chemists, and engineers to establish modern industrial biotechnology, based on products such as organic solvents and antibiotics. During and after this period, many ground-breaking discoveries and developments were made by biochemists, geneticists, and cell biologists and gave rise to molecular biology. At this point, the stage was set for modern biotechnology, based on genetic and cell engineering, to come into being during the 1970s and ’80s. With the advent of information technology, finally, modern biotechnologies gave rise to genomics, proteomics and cellomics, which promise to develop into the key technologies of the 21^st century, with a host of applications in medicine, food and agriculture, chemistry and environmental protection.

Early pioneers and products. Biotechnology is an applied science – many of its developments are driven by economic motives. In 1864 Louis Pasteur, a French chemist, used a microscope for the first time to monitor the fermentation of wine vs. lactic acid. Using sterilized media (“pasteurization”), he obtained pure cultures of microorganisms, thus laying the foundation for applied microbiology and expanding this field into the control of pathogenic microorganisms. At the start of the 20^th century, it occurred to the German chemist Otto Roehm and to the Japanese scientist Jokichi Takamine that enzymes isolated from animal wastes or from cultures of molds might be useful catalysts in industrial processes. Otto Roehm’s idea revolutionized the tanning industry, since tanning up to this time was done using dog excrements. In the field of public health, the introduction of biological sewage treatment around 1900 was a milestone for the prevention of epidemics. During World War I, Carl Neuberg in Germany and Chaim Weizmann, a Russian emigrant to Britain and of Jewish origin, developed large-scale fermentation processes for the preparation of ammunition components (glycerol for nitroglycerol and acetone for Cordite). The Balfour declaration and the ensuing foundation of the state of Israel, whose first president Weizmann became, is thus directly linked to an early success in biotechnology. In the postwar period, 1-Butanol, the second product from Weizmann’s Clostridium-based fermentation process, became highly important in the USA as a solvent for car paints. The serendipitous discovery of penicillin by Alexander Fleming (1922), much later turned into a drug by Howard Florey, initiated the large-scale production of penicillin and other antibiotics during World War II. As early as 1950, > 1000 different antibiotics had been isolated and were increasingly used in medicine, in animal feeds, and in plant protection. This was accompanied by a rising tide of antibiotic resistance, triggering research on the mechanisms of microbial defense mechanisms. Since 1950, the analytical use of enzymes, later of antibodies, began another important field of modern biotechnology. The first glucose biosensor was introduced by Leland C. Clark in 1954, initiating a concept for blood glucose monitoring which now commands a market of several billion US-$. In the shadow of the 1960s’ oil crises and the emerging awareness of overpopulation, the conversion of biomass to energy such as bio-ethanol and of single-cell protein from petroleum or methanol was developed. Now, in 2014, “biorefineries” are under active development.

Biotechnology today

Genetic Engineering and Cell Technology. In 1973, Stanley Cohen and Frederick Boyer in San Francisco were the first to express a designed foreign gene in a host organism. After about 10 years the first recombinant drug, human somatotropin, was registered. Since then, more than 50 genetically engineered proteins have been registered as therapeutic agents, including insulin (for diabetics), erythropoietin (for anemic patients), factor VIII (for hemophiliacs), interferon-β (for multiple sclerosis patients), recombinant antibodies and vaccines. Many hundred more are under development. Although the new technologies were first applied to medicine, their innovation potential in agriculture and food production soon began to emerge. Thus, transgenic crops were bred that were resistant to herbicides, insects, or viruses. Today, they are predominantly grown in North America. Flowers have been genetically modified to exhibit new colors, vegetables or fruits to show enhanced nutritive properties, and woods to contain less lignin for improved paper production. In the chemical industry, biopolymers, prepared from biomass-derived chemicals such as starch or cellulose, have begun to replace petrochemical products, and “biorefineries” have appeared which generate biofuels and chemicals from biomass. These technologies are changing the face of agriculture. High-throughput gene sequencers and supercomputers are making the sequencing of human genomes relatively cheap and routine, and genome-based information is now widely used to understand the molecular basis of diseases and to develop novel drugs by a target-oriented screening approach. Novel approaches, such as proteomics and structural biology, are contributing to our fundamental understanding of the chemistry of life and disease. Using gene therapy, we attempt to replace malfunctioning with correctly functioning genes. These developments are in step with great advances in cell biology, which focus on the complex interactions of cells in a multicellular organism. Human differentiated cells such as cardiomyocytes or neurons can now be obtained from embryonal stem cells or even from adult human cells by genetic reprogramming via induced pluripotent stem cells (iPS). Tissue engineering has become a surgical approach to repairing wounded tissue such as skin, bone or cartilage.

Public acceptance. The sheep Dolly, born in 1998, was the first animal ever cloned from a somatic cell of and thus identical to her mother. The thrust and possible consequences of such developments, e. g., for embryonic manipulations or individual (prenatal) genetic fingerprinting, have led to emotional public discussion. Typical subjects are: at what stage does human life begin and when does it need to be protected? Do we accept the cloning of humans? To which extent can we accept a deterministic view of individual health risks, e. g., by an employer or an insurance company? How will molecular genetics and gene therapy affect the age distribution in our societies? Is it ethical to genetically modify plants and animals at will? To what extent are such manipulations in harmony with the ecosystem and its natural diversity? How will the new biotechnologies influence the relationship of industrialized and developing economies? None of these questions has been completely resolved yet. As we begin to understand and interfere with the functions of the human brain, answering these questions on a global scale will become even more urgent.

Foundations. The body of this pocket guide is devoted to the many and growing applications of biotechnology, including discussion of today’s “megatrends” (2014), which include bioinformatics. In the introduction to this book, however, the multidisciplinary foundations of the field are briefly outlined. We start with microbiology, which is the oldest discipline and has led the way to many contemporary technologies. This is followed by biochemistry, the science of life’s building blocks, their metabolism and its regulation. A key property of life is to propagate. As a consequence, the basics of molecular genetics and genetic engineering will be presented. Cell biology and immunology continue to have a great impact on biotechnology, and some basics are introduced. Finally, without bioprocess engineering, a discipline mastered by engineers, the manufacturing of bioproducts could not be done in an economical way. It is obvious that the space available does not allow a thorough discussion of all these fields, but current literature will be provided to the reader interested in further reading.