2008 PREMIO LETTERARIO InTERnAzIOnALE MOnDELLO
Euskaltzaindia (Royal Academy of the Basque Language)
Technion (Israel Institute of Technology), haifa, Israel
21st century. Are we going to cure all diseases?
I The flight lasted eight hours, and it took a further two hours to get out of the airport and
Many important drugs such as penicillin, aspirin, or digitalis, were discovered by serendipity — some
find the car that had come to fetch us. Our daughters were exhausted, and the youngest,
by curious researchers who noted an accidental phenomenon, some by isolation of active ingre-
who was then only three, immediately fell asleep. not so our eldest, who was five at the time.
dients form plants known for centuries to have a specific therapeutic effect. Other major drugs
‘I’m thinking,’ she said after a while, when we asked why she couldn’t sleep. She added that
like statins were discovered using more advanced technologies, such as targeted screening, yet,
something odd had happened. ‘I didn’t see the people,’ she said. ‘All that time travelling
the discoverers were looking for a different effect. In all these cases, the mechanisms of action
through the sky and I didn’t see them. ’ We asked her which people she was referring to: ‘The
were largely unknown at the time of their discovery, and were discovered only later. With the
people who are dead,’ she answered.
realization that not all patients with diseases that physically and histopathologically appear to be
the same —different malignancies for example— respond similarly to treatment, and their clinical
II We were driving across the Arizona desert. Fancifully shaped rocks rose out of the earth
behavior is different, we have begun to understand that their molecular basis is distinct. Accordingly,
like small islands in a reddish sea. There wasn’t a cloud in the sky.
we are exiting the era where our approach to treatment is “one size fits all”, and enter a new one
We told the girls to look out of the car window and contemplate that landscape so different
of “personalized medicine” where we shall tailor the treatment according to the patient’s molecu-
from our own and from that of any other country in Europe. They did as asked, but, being
lar/mutational profile. here, unlike the previous era, the understanding of the mechanism will drive
children, only long enough to appear to be obeying before getting back to their own affairs,
the development of the new drugs. This era will be characterized the development of technologies
which are rarely contemplative. We tried again and spoke of the members of our family who
where sequencing and processing of individual genomes will be cheap (US$ <1,000) and fast (a
had never made a journey like that. ‘They would be amazed to see this desert. Look how big
few min), by identification and characterization of new disease-specific molecular markers and
drug targets, and by design of novel, mechanism-based, drugs to modulate the activities of these
targets. It will require a change in our approach to scientific research and development and to edu-
‘I really really wish Ignacio was here,’ our youngest daughter said suddenly; she was eight by
cation, where interdisciplinarity will domineer and replace in many ways the traditional, discipline-
then. She was referring to a friend of whom she was very fond and who had died shortly be-
aaron ciechanover was born in Haifa (israel). He received his Msc (1971) and Md (1975) from the Hebrew
We all hastened to agree, especially her older sister, who was now ten. Aware of her respon-
university in Jerusalem, and his dsc (1982) from technion of which he is a distinguished research
sibilities, she said: ‘Ignacio went to heaven, so he won’t feel any need to see the desert.’
Professor. there, as a graduate student with Prof. avram Hershko and in collaboration with Prof. irwin
I supported this point of view. I spoke of Ignacio’s long life and the good times we had en-
a. rose from the fox chase cancer center in Philadelphia, Pennsylvania (usa), they discovered that
joyed together. I resorted to the same metaphor: ‘Don’t you worry. Ignacio will be very happy
covalent attachment of ubiquitin to a target protein signals it for degradation. they deciphered the
mechanism of conjugation, described the general proteolytic functions of the system, and proposed a
‘I’m not so sure,’ she said. ‘It can’t be very nice being so high up.’
model according to which this modification serves as a recognition signal for a specific downstreamprotease. as a post doctoral fellow with Prof. Harvey lodish at the Massachusetts institute of technol-
Bernando atxaga graduated in economics from the university of the Basque country. Mr. atxaga is
ogy (Mit) in cambridge, Massachusetts, Prof. ciechanover continued his studies on the ubiquitin sys-
internationally acclaimed as one of the major writers in euskara, the Basque language. He is the most
tem. through further research it became clear that ubiquitin-mediated proteolysis plays major roles in
widely translated Basque writer and has been awarded the most number of prizes. among his many
numerous cellular processes, and aberrations in the system underlie the pathogenetic mechanisms of
awards include: the euskadi Prize (1989, 1997, 1999), the spanish fiction award (1989), Paris Milepages
many diseases, among them certain malignancies and neurodegenerative disorders. consequently,the system has become an important platform for drug development. among the numerous prizes
(1991), the atlantic Pyrenees three crowns award (1995), the eusko ikaskuntza Prize (2002), the cesare
Prof. ciechanover has received are: the 2000 albert lasker award, the 2003 israel Prize, and the 2004
Pavese award for Poetry (2003), the Mondello Prize for international literature (2008) and the grinzane
nobel Prize in chemistry which was shared with Prof. Hershko and Prof. rose. ciechanover is member
cavour Prize (2008) and the spanish critics’ Prize (1978, 1985, 1988, 1993, 2003). He regularly lectures
of the israeli national academy of sciences and Humanities, the Pontifical academy of sciences of the
at universities around the world and appears as an essential author on lists of 21st century writers such
Vatican, the american academy of arts and sciences, the national academy of sciences (usa), and
as the observer’s “21 top writers” list of 1999.
the institute of Medicine of the national academy of sciences.
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