Werner Arber –
AutobiographyWerner Arber –
AutobiographyI was born on June 3rd, 1929 in Gränichen in the Canton
of Aargau, Switzerland, where I went to the public schools until the age of
16. I then entered the gymnasium at the Kantonsschule Aarau where I got a B-type
maturity in 1949. From 1949 to 1953 I studied towards the diploma in Natural
Sciences at the Swiss Polytechnical School in Zurich. It is in the last year
of this study that I made my first contacts with fundamental research, when
working on the isolation and characterisation of a new isomer of Cl34,
with a halflife of 1.5 seconds.On the recommendation of my professor in experimental
physics, Paul Scherrer, I took an assistantship for electron microscopy at the
Biophysics Laboratory at the University of Geneva in November 1953. This laboratory
was animated by Eduard Kellenberger and it had two prototype electron microscopes
requiring much attention. In spite of spending many hours to keep the microscope
"Arthur" in reasonable working condition, I had enough time not only to help
developing preparation techniques for biological specimens in view of their
observation in the electron microscope, but also to become familiar with fundamental
questions of bacteriophage physiology and genetics, which at that time was still
a relatively new and unknown field. My first contribution to our journal club
concerned Watson and Crick's papers on the structure of DNA.
In the 1950's the Biophysics Laboratory at the University of Geneva was lucky
enough to receive each summer for several months the visit of Jean Weigle. He
was the former professor of experimental physics at the University of Geneva.
After having suffered a heart attack, he had left Geneva to become a researcher
at the Department of Biology of the California Institute of Technology in Pasadena.
There, he had been converted to a biologist under the influence of Max Delbrück
and had chosen to study bacteriophage lambda. This is why the first electron
micrographs of phage lambda were made in Geneva. Stimulated by Jean Weigle we
soon turned our interests also to other properties of lambda, and the study
of defective lambda prophage mutants became the topic of my doctoral thesis.
In the summer of 1956, we learned about experiments made by Larry Morse and
Esther and Joshua Lederberg on the lambda-mediated transduction (gene transfer
from one bacterial strain to another by a bacteriophage serving as vector) of
bacterial determinants for galactose fermentation. Since these investigators
had encountered defective lysogenic strains among their transductants, we felt
that such strains should be included in the collection of lambda prophage mutants
under study in our laboratory. Very rapidly, thanks to the stimulating help
by Jean Weigle and Grete Kellenberger, this turned out to be extremely fruitful.
We could indeed show that lambda-mediated transduction is based on the formation
of substitution mutants, which had replaced a part of the phage genes by genes
from the bacterial chromosome. This made the so-called lambda-gal phage derivatives
so defective that they were not able any longer to propagate as a virus. In
fact, one of the at first sight rather frustrating observation was that lysates
of lambda-gal, which indeed could still cause the infected host cell to lyse
as does wild type phage lambda, did not contain any structural components of
lambda (phage particles, heads or tails) discernible in the electron microscope.
This was the end of my career as an electron microscopist and in chosing genetic
and physiological approaches I became a molecular geneticist.
After my Ph. D. exam in the summer of 1958 I had the chance to receive an offer
to work at the University of Southern California in Los Angeles with Joe Bertani,
a former collaborator of Jean Weigle. Several years before, Bertani had isolated
and characterised another bacteriophage of E. hard animalsex Werner Arber galleries gays - Autobiography with free Werner Autobiography gays free galleries Arber - with hard animalsex - abduction Werner rape stories Arber Autobiography free Werner Autobiography - risque lingerie Arber female - Arber fantasies Autobiography rape Werner Arber Трансформатор - Werner Autobiography ТМ под проставки т по Werner салону д - короба разное Autobiography Arber опоры саб и стойки coli, P1. Phage P1 rapidly
had become a very welcome tool of bacterial geneticists, since it gives general
transduction, i.e. any particular region of the host chromosome gets at some
low frequency wrapped into P1 phage particles if P1 multiplies in a cell, and
this enables the geneticists to carry out linkage studies of bacterial genes.
While working as a research associate with Bertani, I received P1 at first hand
which enabled me to study phage Pl-mediated transduction of monomeric and dimeric
lambda prophage genomes as well as of the fertility plasmid F.
In the meantime, my Ph. D. thesis on lambda-gal, although written in French,
had been read, or, what is perhaps more essential, understood in its conclusions
by many leading microbial geneticists.
This may be the reason why I received offers to spend additional postdoctoral
time in several excellent laboratories. On the other hand, I had remained in
close contact with Eduard Kellenberger, and he urged me to come back to Geneva
in order to lead an investigation on radiation effects on microorganisms. As
a compromise, I decided to return to Geneva at the beginning of 1960, but only
after having spent several very fruitful weeks at each of the laboratories of
Gunther Stent in Berkeley, Joshua Lederberg in Stanford and Salvador Luria at
the Massachusetts Institute of Technology, Cambridge.
At the end of the 1950's, a special credit had been voted for by the Swiss Parliament
for research in atomic energy, including radiation effects on living organisms.
Eduard Kellenberger felt that important contributions to the latter questions
could be expected from studies with microorganisms, and he had therefore submitted
a research proposal which found approval by the granting agency, the Swiss National
Science Foundation. The project could bring insight into the nature of radiation
damage to genetic material and its repair mechanisms, as well as of the stimulation
of genetic recombination by radiation. These topics had already engaged the
attention of Jean Weigle and Grete Kellenberger for a number of years.
One of the first experiments after my return to Geneva was to render E. coli
B and its radiation resistant strain B/r sensitive to phage lambda. The first
step to accomplish this was easy thanks to a hint received from Esther Lederberg
to look for cotransduction of the Ma1+ and lambdaS characters.
However, the strains thus obtained still did not allow an efficient propagation
of lambda. Very rapidly I realized that this was due to host-controlled modification,
a phenomenon described for lambda and E. coli strains seven years earlier
by Joe Bertani and Jean Weigle. However, I was not satisfied to know how to
overcome this barrier. I was also anxious to know how the restriction of phage
growth and the adaptation of lambda to the new host strain worked. When I started
investigations on the mechanisms of host-controlled modification, I did not
of course imagine that this sidetrack would keep my interest for many years.
Otherwise I might not have felt justified to engage in this work because of
its lack of direct relevance to radiation research. However, a lucky coincidence
rapidly dissipated these concerns. At the same time, Grete Kellenberger had
looked at the fate of DNA from irradiated phage lambda upon infection of host
bacteria: part of it was rapidly degraded after injection into the host. And
so was the DNA from unirradiated phage lambda used to measure adsorption and
DNA injection into restrictive bacterial strains! This phenomenon became the
topic of Daisy Dussoix's doctoral thesis, who very carefully not only studied
the DNA degradation of phage that was not properly modified, but who also tried
to detect parallels between the fate of unmodified DNA in restrictive conditions
and of irradiated DNA in normal host cells.
Within about one year of study, it had become clear that strain-specific restriction
and modification directly affected the DNA, without however causing mutations.
It soon also became obvious that restriction and modification were properties
of the bacterial strains and acted not only on infecting bacteriophage DNA,
but also on cellular DNA as manifested in conjugation experiments. These findings
were reported by myself and Daisy Dussoix for the first time to the scientific
community during the First International Biophysics Congress held in Stockholm
in the summer of 1961. In a more extended version I presented them in 1962 to
the Science Faculty of the University of Geneva as my work of habilitation as
privatdocent. This work earned me in the same year the Plantamour-Prévost
prize of the University of Geneva.
At a time before the Swiss Universities received direct financial help from
the federal government, the Swiss National Science Foundation awarded "personal
grants" to qualified researchers to allow them to guide projects of fundamental
research at a Swiss University. I was lucky to benefit from such a support form
1965 to 1970. These years were devoted to hard work to consolidate the preliminary
data and the concepts resulting from them, and to extend the acquired notions,
in particular with regard to the mechanisms of modification by nucleotide methylation,
with regard to the genetic control of restriction and modification and with
regard to the enzymology and molecular mechanisms of these reactions.
This work would not have been possible without a very fruitful help by a large
number of collaborators in my own laboratory and of colleagues working on related
topics in their own laboratories. I was extremely lucky to receive in my laboratory
in the basement of the Physics Institute of the University of Geneva a number
of first class graduate students, postdoctoral fellows and senior scientists.
It is virtually impossible to list them all in this context, but my warmest
collective thanks go to all of them. In 1964 Bill Wood laid out a solid basis
for the genetics of the restiction and modification systems EcoK and
EcoB. Later, Stuart Linn, profiting from his fruitful contacts with Bob
Yuan and Matt Meselson, who worked in the USA on the enzymology of EcoK
restriction, set the basis for in vitro studies with EcoB restriction
and modification activities. These studies culminated in the final proof that
modification in E. coli B and K is brought about by nucleotide methylation.
This concept had found its first experimental evidence during my two months'
visit in 1963 with Gunther Stent at the University of California in Berkeley.
Several years later Urs Kühnlein, a Ph. D student, and John Smith, working
for various lengths of time with us, succeeded in careful in vivo and in vitro
measurements on methylation to validate and extend the earlier conclusions.
Their experiments also brought important conclusions with regard to the concept
of the sites of recognition on the DNA for the restriction and modification
enzymes.
As an illustration that my work has not always been easy and accompanied by
success, I would like to refer to my long, fruitless and thus largely unpublished
attempts to find experimental evidence for the diversification of restriction
and modification systems in the course of evolution. Systems EcoK and
EcoB form a closely related family as judged from genetic and functional
studies. Another family is formed by restriction and modification systems EcoP1
and EcoP15. One could expect that mutations affecting the part of the
enzymes responsible for recognition of the specificity site on the DNA might
result in new members of the family, recognizing new specificity sites on DNA.
We have in vain spent much time in search for such evolutionary changes both
after mutagenization and after recombination between two members of the same
family of the above mentioned systems. That the basic idea for this search was
good was recently shown by Len Bullas, Charles Colson and Aline van Pel (J.
Gen. Microbiol. 95, 166- 172, 1976) who encountered such a new system in their
work with Salmonella recombinants.
In 1965 I was promoted extraordinary professor for molecular genetics at the
University of Geneva. Not only did I always enjoy a continued contact with the
students, but I also considered teaching as a welcome obligation to keep my
scientific interests wide. Although we had a few excellent students in our laboratories,
the teaching of molecular genetics at the University of Geneva in the 1960's
suffered a bit from a lack of interest by the young generation. This might have
been related to a more general lack of public interest for this field, which
was perhaps due to the economic structure of the city of Geneva and its environments.
These, at that time perhaps more subconscious concerns, might have helped me
to accept in 1968 an offer for a professorship at the University of Basel, since
I felt that more general interest would be given to molecular genetics in this
city with a long tradition of biomedical research at its industries.
I started my new appointment at the University of Basel in October 1971 after
having spent one year as a visiting Miller Research Professor at the Department
of Molecular Biology of the University of California in Berkeley. In Basel,
I was one of the first persons to work in the newly constructed Biozentrum,
which houses several University Departments, in particular those of Biophysics,
Biochemistry, Microbiology, Structural Biology, Cell Biology and Pharmacology.
This diversity within the same house largely contributes to fruitful collaborative
projects and it helps to keep horizons broad both in research and teaching.
Additional contributions to this goal come from contacts with other nearby University
Institutes as well as with the private research Institutions in the city.
Since my coming to Basel, I devoted relatively little of my time to further
studies on restriction and modification mechanisms. Not that I have lost my
interest in them. On the contrary, I was fortunate to be able to set up a junior
group which under the leadership of Bob Yuan and more recently of Tom Bickle,
became rapidly quite independent, and it continues to be very successful in
its investigations on the more detailed aspects of the molecular mechanisms
of restriction and modification. This allowed me to turn my main interests back
to other mechanisms affecting either positively or negatively the exchange of
genetic material. For a number of years Nick Gschwind, a Ph. D. student, and
Dorothea Scandella, a postdoctoral fellow, explored two other mechanisms found
in some E. coli strains or mutants and affecting more specifically than
restriction and modification systems particular steps in the propagation of
bacteriophage lambda.
For the last several years I have turned my principal interests to the intriguing
activities of insertion elements and transposons, which by their actions on
genetic rearrangements, seem to be the main driving forces of evolution in microorganisms.
Because of their independence on extended nucleotide homologies these forces
bring about exchange of largely unrelated genetic materials. Our postdoctoral
workers Katsutoshi Mise, Shigeru Iida and Jürg Meyer brought important
contributions to the understanding of these phenomena, mainly by the use of
the bacteriophage P1 genome as a natural vector of transposable elements. But
general knowledge on this to my mind extremely important field is still very
scarce and deserves continued attention.
Solid notions on naturally occurring genetic exchange between organisms that
are not directly related will also form a good basis for a scientific evaluation
of conjectural risks of in vitro recombinant DNA research. Since this research
largely makes use of restriction enzymes, although it in no way fully depends
on them, I consider it a personal obligation to contribute to the best of my
abilities to the solution of questions which arose in the scientific and public
debate on this research in the last few years. I see two ways to reach this
goal. The first is scientific and tends as just stated to better understand
what nature does in its nonhomologous genetic exchange. The second is rather
political and it consists in actions to stimulate continued awareness of responsibility
to work with a maximum of care in all scientific investigations, which should,
however, be allowed to be done under optimal academic freedom.
A curriculum vitae would be incomplete without reference to my private life.
I am fortunate to have found a continued support and steady encouragement by
my family, in particular by my parents, and, since we became married in 1966,
by my wife Antonia. In response to their interest and understanding for my scientific
activities, I have tried to give them my personal affection needed for a harmonious
life. Our two daughters Silvia and Caroline were born in 1968 and in 1974, respectively.
When Silvia learned that I had been honored by the Nobelprize she not only wanted
to know what this is, but also why I was chosen as a Laureate. After explaining
her in simple terms the basic concepts of the mechanisms of restriction enzymes,
she, after some reflection, reexpressed this message in her own terms by a tale,
which in the meantime has found wide diffusion around the world. It might thus
be justified to finish this curriculum vitae by its reproduction:
"The tale of the king and his servants
When I come to the laboratory of my father, I usually see some plates lying
on the tables. These plates contain colonies of bacteria. These colonies remind
me of a city with many inhabitants. In each bacterium there is a king. He is
very long, but skinny. The king has many servants. These are thick and short,
almost like balls. My father calls the king DNA, and the servants enzymes. The
king is like a book, in which everything is noted on the work to be done by
the servants. For us human beings these instructions of the king are a mystery.
My father has discovered a servant who serves as a pair of scissors. If a foreign
king invades a bacterium, this servant can cut him in small fragments, but he
does not do any harm to his own king.
Clever people use the servant with the scissors to find out the secrets of the
kings. To do so, they collect many servants with scissors and put them onto
a king, so that the king is cut into pieces. With the resulting little pieces
it is much easier to investigate the secrets. For this reason my father received
the Nobel Prize for the discovery of the servant with the scissors".
This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures. The information is sometimes updated with an addendum submitted by the Laureate. To cite this document, always state the source as shown above.