Biotechnology for Beginners

426 Pages·2016·203.33 MB·English

by  Reinhard Renneberg

Biotechnology
for Beginners
Second Edition
Reinhard Renneberg
Viola Berkling
Vanya Loroch
Darja Süßbier (Illustrations)
B
iotechnology
B
for eginners
Second Edition
Edited by Arnold L. Demain
Professor emeritus of Massachusetts Institute of Technology (MIT),
at present Research Fellow, Research Institutes for Scientists Emeriti
(RISE), Drew University
Foreword by Tom A. Rapoport
Harvard Medical School
Translated from German by
Renate FitzRoy
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Copyright © 2017, 2008 Elsevier Inc. All rights reserved.
Translation from the German language edition: Biotechnologie für nsteiger
By Reinhard Renneberg and Viola Berkling
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T
here is noThing so powerful
.
as an idea whose Time has come
Victor Hugo
i ,
n The fields of observaTion
.
chance favors only The prepared mind
Louis Pasteur
i
predicT ThaT The domesTicaTion of bioTechnology

will dominaTe our lives
50
during The nexT years

aT leasT as much as

The domesTicaTion of compuTers

has dominaTed our lives
50 .
during The pasT years
Freeman Dyson
FOR MY WONDERFUL MOTHER,
ILSE RENNEBERG,
THIS BOOK IS DEDICATED TO HER WITH LOVE AND GRATITUDE
Sanger Institute Cambridge (top)
and in his basement laboratory
during the sequencing of insulin.
A Letter from Cambridge
Frederick Sanger was one of the heroes of my childhood.
I admired his sharp intellect, his perseverance when
working in his basement lab and analyzing insulin, his
modesty and, of course, his achievement of receiving two
Nobel Prizes.
As soon as this book was published, I sent him a copy
by courier on the off chance he would read it, not really
expecting a reply.
Four months later, a hand-written letter by the then
87-year-old arrived.
If you are a student reading this, be aware that Fred
Sanger would have loved to be one of you!
After all, the biotech revolution has just begun.
I wish you good luck, success, and a happy journey of
discovery!
Fred Sanger in his lab investigating Reinhard Renneberg
the insulin structure
C
ontributors
Contributions to the Whole Martin Holtzhauer, IMTEC, Berlin-Buch,
Book Germany
Jon Huntoon, The Scripps Research Insitute,
La Jolla, CA, United States
Francesco Bennardo, Liceo Scientifico Frank Kempken, Christian-Albrechts-
S. Valentini, Andreotta, CS, Italy Universität, Kiel, Germany
Ming Fai Chow, Hong Kong Albrecht F. Kiderlen, Robert-Koch-Institut,
Jan Frederick Engels, HKUST, Hong Kong Berlin, Germany
David S. Goodsell, The Scripps Research Uwe Klenz, Institut für Physikalische
Institute, La Jolla, CA, United States Hochtechnologie e.V., Jena, Germany
Oliver Kayser, TU Dortmund, Dortmund, Louiza Law, Hong Kong
Germany Inca Lewen-Dörr, GreenTec., Köln, Germany
Oliver Ullrich, Hochschule für Angewandte Hwa A. Lim, D’Trends Inc., Silicon Valley, CA,
Wissenschaften, Hamburg, Germany United States
Jutta Ludwig-Müller, Technische Universität
Contributions to Single Dresden, Dresden, United States
Stephan Martin, Deutsches Diabetes-Zentrum
Chapters an der Heinrich-Heine-Universität Düsseldorf, James Watson, the master, spoke these wise
Düsseldorf, Germany words…if you want to know what else he has to
say - look at page TKTK
Rita Bernhardt, Universität des Saarlandes, Alex Matter, Berlin, Germany
Saarbrücken, Germany Wolfgang Meyer, Berlin, Germany
Uwe Bornscheuer, Ernst-Moritz-Arndt- Marc van Montagu, Max-Planck-Institut für Eckhard Wellmann, Universität Freiburg,
Universität, Greifswald, Germany Pflanzenzüchtung, Köln, Germany Freiburg, Germany
George Cautherley, R&C Biogenius, Werner Müller-Esterl, Präsident der Johann- Michael Wink, Ruprecht-Karls-Universität
Shaukeiwan, Hong Kong Wolfgang-Goether- Universität, Frankfurt am Heidelberg, Heidelberg, Germany
Ananda Chakrabarty, University of Illinois, Main, Frankfurt, Germany Dieter Wolf, Boehringer-Ingelheim, Biberach,
Chicago, IL, United States Reinhard Niessner, Technische Universität Germany
Emmanuelle Charpentier, MPI Infection München, München, Germany Leonhard Zastrow, Coty International Inc.,
Biology, Berlin, Germany Susanne Pauly, Hochschule Biberach, Biberach Monaco, France
King Chow, HKUST, Hong Kong an der Riß, Germany
David P. Clark, Southern Illinois University, Jürgen Polle, Brooklyn College of the City
Chicago, IL, United States University, Brooklyn, NY, United States Experts’ Boxes and Biotech
Arnold L. Demain, Drew University, Madison, Tom A. Rapoport, Harvard Medical School,
History Contributions
NJ, United States Boston, MA, United States
Theodor Dingermann, Johann Wolfgang Matthias Reuss, Universität Stuttgart,
Goethe-Universität, Frankfurt am Main, Stuttgart, Germany Wolfgang Aehle, B.R.A.I.N. AG, Zwingenberg,
Germany Hermann Sahm, Forschungszentrum Jülich, Germany
Stefan Dübel, Technische Universität Jülich, Germany Werner Arber, Basel, President of the Papal
Braunschweig, Braunschweig, Germany Frieder W. Scheller, Universität Potsdam, Academy of Sciences, Vatican City
Roland Friedrich, Justus-Liebig-Universität Potsdam, Germany Susan R. Barnum, Miami University, Oxford,
Gießen, Gießen, Germany Steffen Schmidt, Berlin, Germany OH, United States
Peter Fromherz, Max-Planck-Institut für Olaf Schulz, Interventionelle Kardiologie Hildburg Beier, Universität Wüzburg, Wüzburg,
Biochemie, Martinsried/München, Germany Spandau, Berlin, Germany Germany
Dietmar Fuchs, Universität Innsbruck, Georg Sprenger, Universität Stuttgart, Ian and John Billings, Norwick Philatelics,
Innsbruck, Austria Stuttgart, Germany Dereham (GB), United Kingdom
Saburo Fukui†, Kyoto University, Kyoto, Japan Eric Stewart, INSERM – University Paris 5, Ananda M. Chakrabarty, University of Illinois,
Karla Gänßler, Gerswalde, Germany Paris, France Chicago, IL, United States
Oreste Ghisalba, Ghisalba Life Sciences GmbH, Gary Strobel, Montana State University, Cangel Pui Yee Chan, Chinese University of Hong
Reinach, Switzerland Bozeman, MT, United States Kong, Prince of Wales Hospital, Hong Kong
Horst Grunz, Universität Duisburg, Essen, Kurt Stüber, Köln, Germany David P. Clark, Southern Illinois University,
Germany Atsuo Tanaka, Kyoto University, Kyoto, Japan Carbondale, IL, United States
Georges Halpern, University of California, Dieter Trau, National University of Singapore, Charles Coutelle, Imperial College, London
Davis, CA, United States Singapore Jared M. Diamond, UCLA, Los Angeles, CA,
Albrecht Hempel, Zentrum für Energie- & Thomas Tuschl, Rockefeller University, New United States
Umweltmedizin, Dresden, Germany York, NY, United States Carl Djerassi†, Stanford University, Stanford,
Choy-L. Hew, National University of Singapore, Larry Wadsworth, Texas A&M University, CA, United States
Singapore College Station, TX, United States Stefan Dübel, Technische Universität
Franz Hillenkamp, Universität Münster, Terence S.M. Wan, The Hong Kong Jockey Club, Braunschweig, Braunschweig, Germany
Münster, Germany Hong Kong Akira Endo, Tokyo University, Tokyo, Japan
Bertold Hock, Technische Universität München, Zeng-yu Wang, The Noble Foundation, Herrmann Feldmeier, Institut für Mikrobiologie
München, Germany Ardmore, Oklahoma und Hygiene der Charité, Berlin, Germany
ix
Ernst Peter Fischer, Universität Konstanz, James W. Larrick, Panorama Research Institute, Gerd Spelsberg, TransGen, Aachen, Germany
Konstanz, Germany Silicon Valley, CA, United States Gary A. Strobel, Montana State University,
Michael Gänzle, University Alberta, Edmonton, Frances S. Ligler, US Naval Research Lab, Bozman, MT, United States
AB, Canada Washington, DC, United States Jurgen Tautz, BEEgroup, Universität Würzburg,
Erhard Geißler, Max-Delbruck-Centrum für Alan MacDiarmid†, University of Pennsylvania, Würzburg, Germany
Molekulare Medizin Berlin Buch, Berlin Buch, Philadelphia, PA, United States Christian Wandrey, Institut für Biotechnologie,
Germany Dominik Paquet, Medizinische Universität Forschungszentrum Jülich, Jülich, Germany
Oreste Ghisalba, Ghisalba Life Sciences GmbH, München, München, Germany Fuwen Wei, Key Lab of Animal Ecology and
Reinach (Schweiz), Switzerland Uwe Perlitz, Deutsche Bank Research, Frankfurt Conversation Biology, Beijing, China
Susan A. Greenfield, Oxford University, Oxford, am Main, Frankfurt, Germany Katrine Whiteson, San Diego State University,
OH, United States Ingo Potrykus, Humanitarian Golden Rice San Diego, CA, United States
David S. Goodsell, Scripps Research Institute, Board & Network, Schweiz, Switzerland Ian Wilmut, Edinburgh University, Edinburgh,
La Jolla, CA, United States Wolfgang Preiser, Stellenbosch University, United Kingdom
Alan E. Guttmacher, National Institute Stellenbosch, South Africa Michael Wink, Ruprecht-Karls- Universität
of Child Health and Human Timothy H. Rainer, Chinese University of Hong Heidelberg, Heidelberg, Germany
Development (NICHD), Bethesda, MD, Kong, Prince of Wales Hospital, Hong Kong Christoph Winterhalter, Wacker Chemie AG,
United States Jens Reich, Max-Delbruck-Centrum, Berlin, München, Germany
Christian Haass, Deutsches Zentrum für Germany Eckhard Wolf, Universität München, München,
Neurodegenerative Erkrankungen, München, Michael K. Richardson, Universität Leiden, Germany
München, Germany Leiden, Netherlands Boyd Woodruff, Watchung, Somerset, NJ,
Frank Hatzak, Novozymes Dänemark, Stefan Rokem, Hebrew University, Jerusalem, United States
Dänemark Israel Daichang Yang, Wuhan University, Hubei, China
Sir Alec Jeffreys, University of Leicester, Michael Rossbach, Genome Institute of Holger Zinke, B.R.A.I.N. AG, Zwingenberg,
Leicester, United Kingdom Singapore, Singapore Germany
Alexander Kekulé, Universität Halle- Sujatha Sankula, National Center for Food and
Wittenberg, Halle, Germany Agricultural Policy, Washington, DC, United
Shukuo Kinoshita, Tokyo, Japan States
Stephen Korsman, Walter Sisulu University, Gottfried Schatz†, Universität Basel, Basel,
Mthatha, South Africa Switzerland
†Deceased
x
F US e , A d
oreword by the ditor rnold emAin
It is hard to decide when biotechnology began. in awe of the developments of biotechnology
Some would consider dates such as 3500–7000 for many years. Over this time, I have struggled
BC, when microbes were first used to preserve to understand genetic concepts and the new
milk, fruits, and vegetables and to make cheese, aspects introduced by biotechnologists.
bread, beer, wine, pickled foods, and vinegar.
What I needed and never had was a basic
If that was the proper decision, then I have been introductory book on biotechnology.
in biotechnology for my entire adult life, i.e.,
from 1949. At that time, I was 22 years of age and Then, it happened: the book “Biotechnologie fur
starting my Master’s degree research at Michigan Einsteiger” by Reinhard Renneberg was born!
State College (now University) on the spoilage Unfortunately, my German language skills were
of pickles. Also, I would have to consider my virtually nonexistent. However, even without the
grandfather and father as biotechnologists since ability to read the book, I was fascinated by the
they were both “pickle men.” many photos of famous biotechnologists and
scientists and the beautiful color illustrations of
On the other hand, many consider the above Darja Süßbier.
as industrial microbiology and assume that
biotechnology was born in 1972–1973, when How lucky I am that Prof. Renneberg asked me
Paul Berg, Stanley Cohen of Stanford University, to be the editor of the English edition. After
and Herbert Boyer of the University of California translation of the German text into the English
at San Francisco discovered recombinant DNA. by translators Renate FitzRoy and Jackie Jones,
Arnold L. Demain in his office at If this latter view is correct, then I started my I have thus read, word by word, the entire 10
Drew University biotechnology career in 1972, when I was asked chapters of this fantastic effort by Reinhard
to be a consultant for the first biotechnology Renneberg.
company, i.e., Cetus Corporation in Berkeley,
California. Indeed, it was an exciting time I enjoyed every minute of this activity and
during which efforts were put forth to editing the formal English translation into a
There are no two sciences, commercialize the discovery of recombinant version suitable to both young English and
DNA technology. Within 10 years, companies American students has truly been a labor of
there is only one science and such as Genentech, Biogen, Amgen, Genetics love.
its application, and these two Institute, Chiron, and Genzyme were born,
activities are linked as the fruit is and these exciting developments resulted in Arnold L. Demain
the production of recombinant proteins which
to the tree. May 26, 2007
solved medical problems of huge importance
to patients throughout the world. They also led
Louis Pasteur to the development of a huge and important
biotechnology industry which today generates
We have the unity of biochemistry an annual product revenue of over 60 billion
dollars.
on one hand, and the diversity
of microbial life on the other;
I have enjoyed over 50 years of participation in
we have to understand and
both industrial microbiology and biotechnology,
appreciate both. in industry (at Merck & Co) and in academia (at
MIT and recently at Drew University). It always
Arnold L. Demain excited me to design microbes to do important
things and then discover the ways, both genetic,
biochemical, and nutritional, to force these
fantastic microbes to make industrial quantities
of their valuable products, whether they be Dear Master Arny,
antibiotics, amino acids, purine nucleotides,
immunosuppressants, cholesterol-lowering the whole team of Biotechnology for
agents, toxins or recombinant proteins. Beginners wishes to dedicate this book
to your 80th BIRTHDAY celebrated in
I have been fortunate to have mentors, 2007. We are honored to know you
colleagues, and students to help me in these personally and admire your contribution to
efforts. I have always felt that the genetic microbiology and biotechnology, as well
aspects that propelled industrial microbiology as your kindness and wisdom!
into the new world of biotechnology were both
fascinating and fantastic. Reinhard and Merlet, Dascha, Renate,
Jackie, Christoph, Ute, and Ted
Not being a geneticist myself and never even
having taken a course in genetics, I have been
xix
A P F T r
ersonAl oreword by om APoPorT
because they both attended the same school in
his hometown Merseburg. He imitated Haeckel by
establishing a herbarium at home and by becoming
a keen bird and insect spotter. Later, his interest
switched to DNA when a friend gave him the “Double
helix” by Jim Watson, a book that was not available
in the country. He only had it for one night, then he
had to pass it on to the next person in line. The next
day, he made his own DNA model out of colorful
plastic balls used in baby strollers.
After finishing high school, Reinhard wanted to leave
Reinhard Renneberg and Tom Rapoport in Hong Kong. the country for the big wide world. Well, only half the
world was accessible to East Germans, and his first
I admit that I don’t like reading textbooks, and I know choice was China. However, in 1975, relations with
that many students share my reluctance: it requires China were at a low point, and China was undergoing
frustrating diligence to plow through several hundred its “Great Cultural Revolution” anyway. So, he went
pages of accumulated dry knowledge. Modern to the Soviet Union instead. What attracted him
textbooks try their best with their ever-increasing was the big heart of the Russians, their hunger for
number of colorful illustrations, but that still won’t books and art, and their talent for improvisation. He
turn them into thrillers. studied at the Institute for Bioorganic Chemistry in
Moscow, a place that was then a top address.
Thus, when Reinhard Renneberg told me that he
had written a textbook about biotechnology, I was After his return to East Germany, he joined the
skeptical. And when he even asked me to write a Central Institute for Molecular Biology in Berlin-
foreword for it, my first reaction was to turn him Buch, and this is where I met him. He was in Frieder
down: it’s going to be boring, about a subject I have Scheller’s group, working on the development of a
no clue about, and, most important of all, I am busy. biosensor for glucose, a device needed by diabetes
patients for the control of their blood sugar, and
But then I did it anyway, and the bottom line is: although the United States, Great Britain, and Japan
this book is different! Sure, it’s still a textbook and got there first, their success was remarkable, given
conveys knowledge, but it’s really fun to read. the lack of biochemicals, instruments, copying
machines, and many other things that we now take
for granted. Improvisation and a lot of enthusiasm
Reinhard Renneberg and his illustrator Darja Süßbier
Top: Ernst Haeckel in a mural in have packed the facts into excellent illustrations, made up for it!
Merseburg. Bottom: One of Haeckel’s
interesting historical discourses, funny cartoons, and
beautiful nature drawings.
concise texts. An entertaining textbook—this must
be the first of its kind!
I would call it “biotechnology in a nutshell,”
addressed to everyone who is curious about the
latest developments as well as historic foundations.
You really don’t need any particular background for
the book—something like a high school diploma
is sufficient. I am sure you will have the same
experience—being amazed about the wonders of
biology and biotechnology. It’s clear that Reinhard
Merseburg Palace is an impressive late is addicted to the subject, and his enthusiasm is
renaissance building. It was built contagious.
between 1245 and 1265. The palace
stands right next to one of three Saxon
Let me tell you about the author. Reinhard grew up in
cathedrals. Merseburg cathedral is
1,000 years old. the German Democratic Republic, known to people
in the West as “East Germany.” His young parents
became schoolteachers after World War II, thrown
into the job without much training, simply because
there was a teacher shortage due to the ongoing
denazification procedures. Like many others, his
parents embraced the fresh start with enthusiasm
and determination. This upbringing explains
Reinhard’s dedication to teaching.
Grandfather Alfred Schmidt, Divinity student and PhD in
Reinhard had an early love for science books. He told biology at Heidelberg and Halle universities and RR’s role
Ilse Renneberg as a young teacher. me that his first hero was Ernst Haeckel, probably model.
xxi
Soon after the unification of Germany, Reinhard
took a position at the Hong Kong University of
Science and Technology. His former boss, Prof.
Nai-Teng Yu, met him 1994 in East-Berlin and
enthusiastically told his Department: “Hire
Renneberg immediately; the combination
of the high motivation of an East German
with the modern technology in Hong Kong is
unbeatable!” So finally, Reinhard’s dream of
going to China became true.
Prof. Renneberg directs a pretty large research
group that works on the development of
biotests. He also runs a biotech company, owns
two cats and a rabbit, and has a subtropical
garden that overlooks a beautiful bay.
Apparently, he has a lot of spare time because
he writes a regular column, the “Biolumne,” for
a major newspaper, draws cartoons, and always
has a new book project.
The current textbook does not come as a
surprise to me. It’s actually Reinhard’s fourth
book. He started out in East Germany with two
biotechnology books for general readers and
children, and this is where he developed his gift
for clear and entertaining writing.
The book by James Watson that inspired Reinhard to
For me, the most important task of a teacher build his own double helix.
is to convey to the students our passion
for science. Nature has so many wonders
and puzzles, and it’s a privilege that we can
contribute to solving them.
Reinhard’s book certainly conveys the
enthusiasm for science and the belief that it can
do a little bit to improve the world. I wish the
book all the success it deserves.
Tom Rapoport
Boston, June 1, 2007
Reinhard’s research group at Hong Kong University Lomonossov University in Moscow,
of Science and Technology. where Reinhard studied Chemistry.
Tom Rapoport was born 1947 in Cincinnati (USA)
but grew up in East Berlin. He studied chemistry
and biochemistry at the Humboldt University. After
obtaining his PhD, he joined the Central Institute
for Molecular Biology of the Academy of Sciences
of the GDR in Berlin-Buch. In 1985, he became
Professor for Cell Biology, and after the unification of
Germany, group leader at the Max Delbrueck Center
for Molecular Medicine. In 1995, he accepted an
offer from Harvard Medical School in Boston. Since
1997, he is also Investigator of the Howard Hughes
Medical Institute. Tom Rapoport is a member of the
National Academy of Sciences of the United States,
of the American Academy of Arts and Sciences, and of
the Leopoldina Academy, and was awarded several RR’s home since 1995—The Hong Kong University of Science and Technology (HKUST).
prestigious awards and prizes. Now Asia’s No.1 University by international ranking.
xxii