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Memories
of my early childhood are clouded with uncertainties because I was essentially
separated from my parents since the early age of seven. I was born in
Shanghai, China on April 6, 1920. My father had come there from Vienna,
Austria after earning doctorates in law and business. My mother, born
Renée Tapernoux, had arrived from France with her parents via Hanoi. Her
father had left Switzerland as a young man to become a journalist for
L'Aurore. This journal published the letter by Emile Zola entitled "J'accuse"
in which he denounced the government cover-up during the Affaire Dreyfus
which tore France apart at the turn of the century. When the case against
Dreyfus collapsed in the early 1900s my grandfather left for French Indochina,
then called le Tonkin. He later went to Shanghai where he founded the
"Courrier de Chine", the first French newspaper published in China. He
also helped to establish "l'Ecole Municipale Française" where I first
went to school.
At age 7, my parents sent my two older brothers and me to La Châtaigneraie,
a large Swiss boarding school overlooking Lake Geneva. My oldest brother,
Raoul, was the first to leave to attend the ETH, the Swiss Federal Polytechnical
Institute in Zürich where he was awarded a degree in engineering. My brother
Georges went to Oxford and read law.
In 1935, I entered Geneva's all boys Collège de Calvin from which I obtained
my Maturité Fédérale four years later, even as the specter of World War
II loomed evermore menacing. While in school, I formed a lifelong friendship
with my classmate Wilfried Haudenschild who dazzled me with his tinkering
abilities, off-the-wall ideas and mechanical inventiveness. Together we
decided that one of us should go into the Sciences and the other into
Medicine so that we could cure all the ills of the world.
Another important event marked my High School days: I was admitted to
the Geneva Conservatory of Music. I had heard Johnny Aubert give an unforgettable
rendition of Beethoven's 5th Piano Concerto. I decided on the spot that
I wanted to study with him. After an audition in which I nervously presented
Mendelssohn's Rondo Capriccioso and Chopin's A-maj. Polonaise, he took
me on, and that spelled the beginning of many enthralling years. Music
had always played an important part in my life, to such an extent that
I even wondered whether I should not make a career of it. But finally
I thought it better to keep music purely for pleasure.
It was my goal to become a microbiologist but Fernand Chodat, the Professeur
of Bacteriology, argued that there was little future in that field, which
was probably the case in Switzerland at that time. He advised me to get
a diploma in Chemistry saying that, in any case, test tubes were of more
use than a microscope to modern microbiologists.
I therefore entered the School of Chemistry just at the start of World
War II. Two years of quantitative inorganic analyses seemed endless. Organic
chemistry finally arrived like a breath of fresh air, if not a reprieve
on life. I earned two Licences ès Sciences, one in Biology, the other
in Chemistry and, two years later, the Diploma of "Ingénieur Chimiste".
For my thesis, I elected to work with Prof. Kurt H. Meyer, Head of the
Department of Organic Chemistry. "Le Patron" as we affectionately called
him, was a most impressive person. At the time when most scientists showed
little understanding of natural high polymers, Kurt Meyer had already
authored several books on the subject, starting with the epochal "Meyer-Mark:
Der Aufbau der hochpolymeren organischen Naturstoffe" and "Makromolekulare
Chemie". His main interest lay in the structure of polysaccharides, particularly
starch and glycogen. To unravel the structure of these molecules, enzymes
were needed: alpha- and beta-amylases, phosphorylase, etc. Therefore,
the lab was divided into two groups: the enzymologists under the guidance
of Peter Bernfeld and carbohydrate chemists under Roger Jeanloz. I decided
to work on the purification of hog pancreas amylase. Within a couple of
years, we succeeded in crystallizing alpha-amylase from pork pancreas
and soon after that, from a variety of other sources including human pancreas
and saliva, two strains of A. oryzae, B. subtilis and P. saccharophila.
It is at that time that Eric A. Stein joined the laboratory, beginning
a marvelous 15-year collaboration and a lifelong friendship.
It had always been my intention to go to the United States to pursue my
studies in Biochemistry. In those days, that field was in its infancy
in most European universities to such an extent that I was asked to present
the very first course in Enzymology as a Privat Docent at the University
of Geneva in 1950. Two events hastened my departure for the USA: the untimely
death of Kurt Meyer following an asthma attack and my being abruptly issued
a US immigration visa. Apparently, the US consulates abroad were clearing
their files before the complicated McCarran Act would come into effect.
I had decided to go to CalTech on a Swiss Post-doctoral Fellowship that
Professor Paul Karrer succeeded in securing for me on a moment's notice.
Some friends who knew of my arrival in New York had arranged for me to
give some seminars on my way to Pasadena: Maria Fuld at Pittsburgh and
Henry Lardy at Madison. To my utter surprise, I was offered a job in both
places. Then, upon my arrival at CalTech I found a letter from Hans Neurath,
Chairman of the Department of Biochemistry at the University of Washington,
inviting me to come to Seattle, apparently for the same purpose. I thought
that the Americans had to be crazy since at that time, academic positions
in Europe were one-in-a-million. I visited Seattle with my wife and thought
that the surrounding mountains, forests and lakes were beautiful, reminiscent
of Switzerland. The Medical School was brand-new and when I was offered
an Assistant Professorship, I accepted and have never regretted that decision.
There were only seven of us on the faculty and we quickly became close
friends. I remember the amused expressions of my colleagues seated in
the back row of the class listening to my fractured English when lecturing
the medical students. I also remember Ed Krebs' broad smile whenever I
lapsed into French. What Ed didn't realize, though, is that within two
years, while my English didn't improve very much, his deteriorated completely!
Within six months of my arrival, Ed Krebs and I started to work together
on glycogen phosphorylase. He had been a student of the Cori's in St.
Louis. They believed that AMP had to serve some kind of co-factor function
for that enzyme. In Geneva, on the other hand, we had purified potato
phosphorylase for which there was no AMP requirement. Even though essentially
no information existed at that time on the evolutionary relationship of
proteins, we knew that enzymes, whatever their origin, used the same co-enzymes
to catalyze identical reactions. It seemed unlikely, therefore, that muscle
phosphorylase would require AMP as a co-factor but not potato phosphorylase.
We decided to try to elucidate the role of this nucleotide in the phosphorylase
reaction. Of course, we never found out what AMP was doing: that problem
was solved 6-7 years later when Jacques Monod proposed his allosteric
model for the regulation of enzymes. But what we stumbled on was another
quite unexpected reaction: i.e. that muscle phosphorylase was regulated
by phosphorylation-dephosphorylation. This is yet another example of what
makes fundamental research so attractive: one knows where one takes off
but one never knows where one will end up.
These were very exciting years when just about every experiment revealed
something new and unexpected. At first we worked alone in a small, single
laboratory with stone sinks. Experiments were planned the night before
and carried out the next day. We worked so closely together that whenever
one of us had to leave the laboratory in the middle of an experiment,
the other would carry on without a word of explanation. Ed Krebs had a
small group that continued his original work, determining the structure
and function of DPNH-X, a derivative of NADH. I was still studying the
alpha-amylases with Eric Stein. In collaboration with Bert Vallee, we
were able to demonstrate that these enzymes were in reality calcium-containing
metalloproteins.
In those days, we waited all year for the next Federation Meeting or Gordon
Conference. It was an occasion for me to get together with my friends
on the East Coast: Herb and Eva Sober and Chris and Flossie Anfinsen from
NIH, Bill and Inge Harrington from Johns Hopkins, Bert and Kuggie Vallee
from the Brigham and Al and Lee Meister, then at Tufts and later at Cornell,
and many others. I have forgotten much about the meetings themselves.
There was the excitement of hearing about the latest breakthroughs, the
frantic preparations for talks that had to be given, and the numerous
notebooks filled with information, questions and problems that had to
be solved. I will never forget, though, the marvelous time we had together
speaking far into the night about anything and everything. Some of these
friends are gone today but their memory is still vivid.
I have two sons,
François and Henri, from my first wife Nelly Gagnaux, a Swiss National
who died in 1961. I married my present wife Beverley née Bullock from
Eureka, California, in 1963. She has a daughter Paula from a first marriage.
All three of our children are now married and my two sons each has a son.
I received the Werner
Medal from the Swiss Chemical Society, the Lederle Medical Faculty Award;
the Prix Jaubert from the University of Geneva and, jointly with
Ed Krebs,
the Senior Passano Award and the Steven C. Beering Award from Indiana
University. I received Doctorates Honoris Causa from the University of
Montpellier, France and the University of Basel, Switzerland and was elected
to the American Academy of Arts and Sciences in 1972 and to the National
Academy of Sciences in 1973.
From Les Prix Nobel
1992.
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