Cover Page

Rolf D. Schmid

Claudia Schmidt-Dannert


An Illustrated Primer

171 color plates by Ruth Hammelehle

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Prof. Dr. Rolf D. Schmid
Jagdweg 3
70569 Stuttgart

Prof. Dr. Claudia Schmidt-Dannert
University of Minnesota
Department of Biochemistry
1479 Gortner Ave
140 Gortner Lab
St. Paul, MN 55108

Graphic Designer:
Ruth Hammelehle
Marktplatz 5
73230 Kirchheim unter Teck

DNA helix from fotolia

Preface to the 1st edition

Biotechnology, a key technology of the 21st century, is more than other fields an interdisciplinary endeavor. Depending on the particular objective, it requires knowledge in general biology, molecular genetics, and cell biology; in human genetics and molecular medicine; in virology, microbiology, and biochemistry; in the agricultural and food sciences; in enzyme technology, bioprocess engineering, and systems science. And in addition, biocomputing and bioinformatics play an ever-increasing role. Against this background, it is of little surprise that few concise textbooks try to cover the whole field, and important applied aspects such as animal and plant breeding or analytical biotechnology are often missing even from multivolume monographs.

On the other hand, I have experienced during my own life-long studies, and also when teaching my students, how energizing it is to emerge occasionally from the thousands of details which must be learned, to look at a unifying view.

The Pocket Guide to Biotechnology and Genetic Engineering is an attempt to provide this kind of birds-eye perspective. Admittedly, it is daring to discuss each of this book’s topics, ranging from “Beer” to “Tissue Engineering” and “Systems Biology”, on a single text page, followed by one page of graphs and tables. After all, monographs, book chapters, reviews, and hundreds of scientific publications are devoted to each single entry covered in this book (many of them are provided in the literature citations). On the other hand, the challenge of surveying each entry in barely more than 4000 characters forces one to concentrate on the essentials and to put them into a wider perspective.

I hope that I have succeeded at least to some extent in this endeavor, and that you will find the clues to return safely from the highly specialized world of science, and its sophisticated terms, to your own evaluation of the opportunities and challenges that modern biotechnology offers to all of us.

This English version is not a simple translation of the original version, which was published in German in December, 2001, but an improved and enlarged second edition: apart from a general update of all data, it contains three new topics (Tissue Engineering, RNA, and Systems Biology).

At this point, my thanks are due to some people who have essentially contributed to this book. Above all, I wish to acknowledge the graphic talent of Ruth Hammelehle, Kirchheim, Germany, who has done a great job in translating scientific language into very clear and beautiful graphs. Marjorie Tiefert, San Ramon, California, has been more than an editor: she has caught and expressed the original spirit of this book. My thanks also to the publisher, in particular to Romy Kirsten. Special thanks are due to the many colleagues in academia and industry who have contributed their time and energy to read through the entries in their areas of expertise and provide me with most useful suggestions and corrections. These were: Max Roehr, University of Vienna; Waander Riethorst, Biochemie GmbH, Kundl; Frank Emde, Heinrich Frings GmbH, Bonn; Peter Duerre, University of Ulm; Edeltraut Mast-Gerlach, Ulf Stahl and Dietrich Knorr, Technical University Berlin; Udo Graefe, Hans-Knoell Institute, Jena; Jochen Berlin, GBF, Braunschweig; Allan Svenson, Novozymes A/S, Copenhagen; Helmut Uhlig, Breisach; Frieder Scheller, University of Potsdam; Bertold Hock, University of Munich-Weihenstephan; Rolf Blaich, Rolf Claus, Helmut Geldermann and Gerd Weber, University of Hohenheim; Hans-Joachim Knackmuss, Dieter Jendrossek, Karl-Heinrich Engesser, Joerg Metzger, Peter Scheurich, Ulrich Eisel, Matthias Reuss, Klaus Mauch, Christoph Syldatk, Michael Thumm, Joseph Altenbuchner, Paul Keller and Ulrich Kull, University of Stuttgart; Thomas von Schell, Stuttgart; Joachim Siedel, Roche AG, Penzberg; Rolf Werner and Kerstin Maier, Boehringer-Ingelheim, Biberach; Frank-Andreas Gunkel, Bayer AG, Wuppertal; Michael Broeker, Chiron Bering GmbH, Marburg; Bernhard Hauer and Uwe Pressler, BASF AG, Ludwigshafen; Frank Zocher, Aventis Pharma, Hoechst; Tilmann Spellig, Schering AG, Bergkamen; Akira Kuninaka, Yamasa Corporation, Chosi; Ian Sutherland, University of Edinburgh; Julia Schueler, Ernst & Young, Frankfurt. Among the many members of my institute in Stuttgart who have IX patiently helped me with the manuscript I wish to especially acknowledge Jutta Schmitt, Till Bachmann, Jürgen Pleiss and Daniel Appel.

In spite of all efforts and patient cross-checking, it would be a miracle if no unclearness or errors exist. These are entirely the author’s fault. I would be most grateful to all readers who will let me know, via the web address, where this book can be further improved.

Rolf D. Schmid
Stuttgart, New Year 2002/2003

Preface to the 2nd edition

In the 10 years since the first edition of this booklet in English, the developments in biotechnology have further accelerated. This is true for the science, which has generated new methods such as synthetic biology, genome editing or high-throughput sequencing of genomes, generating big data which provide us with ever more detailed perceptions of the living world. New applications in industry have followed suit – in the medical sciences, eminent examples are the therapeutic antibodies, iPS-derived stem-cell technologies or a personalized medicine based on SNP analysis and companion diagnostics; in industrial biotechnology, the emerging concepts of a “bioeconomy” based on renewable resources such as biomass, waste or carbon dioxide provide certainly a megatrend. It goes without saying that a little booklet can only provide short sketches for each of these fields. An updated literature suvey attempts to compensate for this shortcoming.

It is my great joy that Professor Claudia Schmidt-Dannert, University of Minnesota, has accepted to join this and future editions as a co-author. This will help to keep the wide information provided in this book as updated as possible in a global setting.

Our sincere thanks go, beyond the individuals mentioned in the first edition, to numerous friends and colleagues who have helped again with their professional knowledge. Our particular appreciation goes to Wolfgang Wohlleben, Tuebingen University; Karin Benz, NMI Reutlingen; Ulrike Konrad, Protagen; Karl Maurer, ABEnzymes, Darmstadt; Bernhard Hauer, Georg Sprenger and Juergen Pleiss, Stuttgart University; Ulrich Behrendt, Munich; Dirk Weuster-Botz, Munich Technical University; Joern Kalinowsky, Bielefeld University; Vlada Urlacher, Düsseldorf University, and Frieder Scheller, Potsdam University.

The high quality of the artwork is due to Ruth Hammelehle, Kirchheim, of the final editing to Bernhard Walter, both of epline Co., Kirchheim u. T. Our deep thanks to both of them, to the editorial team, Dr Gregor Cicchetti, Dr Andreas Sendtko and Dr Claudia Ley at Wiley-VCH in Weinheim, Germany , and to Dr Sarah Perdue and Dr Bradford Condon at the University of Minnesota, St. Paul. The contribution of Dr Alexandra Prowald, who provided an excellent index to this book, is also highly appreciated.

Rolf D Schmid, Claudia Schmidt-Dannert Stuttgart, Germany and St. Paul, Minnesota, Summer 2015


This pocket guide is written for students of biology, biochemistry and bioprocess engineering who are looking for a short introduction to the many different areas where modern biotechnologies are making an impact. It is also intended as a handy reference for teachers, patent attorneys, managers and investors seeking a quick, yet professional answer surrounding an upcoming topic of industrial biotechnology. To this end, specialized knowledge from a wide range of scientific disciplines has been condensed over a total of 171 color plates and further described on the accompanying text page, as well as complemented by a comprehensive survey of the literature. Cross-references provide additional help in jumping from technical applications of biotechnology, for example, to the fundamental science behind the application.

Completely updated and supplemented by many new topics, this second edition retains the modular format, but the structure of the book has been changed. It now begins, after a brief historical survey, with short introductions to the basic fields of modern biotechnology: microbiology, biochemistry, molecular genetics, cell biology and bioprocess engineering. It is only in the second part that the focus is on applications, such as food and food additives, industrial products, enzyme technology and, most comprehensively, the many contributions of biotechnology to the medical field, including the manufacture of antibiotics, biologicals such as antibodies, but also in medical technology. This section is rounded off with a description of the applications in agriculture, such as animal or plant breeding, and in environmental protection. The third section of the book deals with the current megatrends in the applied life sciences. These include genomics and such post-genomic trends as personalized medicine, with bioinformatics seen as an answer to current needs in big data processing, but also cell technology and gene therapy, as well as technologies devoted to building a new so-called bioeconomy, i. e. sustainable in energy and material use. The text ends with five chapters devoted to various aspects of safety and ethics, including patent and registration-related topics.

The objective of this book is to provide readers with a compact reference on the wide and expanding field of modern biotechnology. We hope that we succeeded not only in offering an attractive and stimulating read, but also in instigating in the reader the desire to dig deeper into this fascinating area of human endeavor.


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 6th 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 19th century. The First and Second World Wars in the first half of the 20th 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 21st 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 20th 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.