Many important drugs such as penicillin, aspirin and digitalis were discovered by serendipity - some by curious researchers who noted an accidental phenomenon, some by isolation of active ingredients form plants known for centuries to have a specific therapeutic effect. Other major drugs like statins were discovered using more advanced technologies, such as targeted screening, yet, the discoverers were looking for a different effect. In all these cases, the mechanisms of action of the drug were largely unknown at the time of their discovery, and were discovered only later. With the realisation that not all patients with diseases that physically and histopathologically appear to be the same - different malignancies for example - respond similarly to treatment, and how their clinical behavior is different, we have begun to understand that their molecular basis is distinct. Accordingly, we are exiting the era where our approach to treatment is “one size fits all”, and enter a new one of “personalised medicine” where we shall tailor the treatment according to the patient’s molecular/mutational profile. Here, unlike the previous era, the understanding of the mechanism will drive the development of the new drugs. This era will be characterised by the development of technologies where sequencing and processing of individual genomes will be cheap (less than US$ 1,000) and fast (a few minutes), by identification and characterisation 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 education, where interdisciplinarity will domineer and replace in many ways the traditional, discipline-oriented approach.
|
Aaron Ciechanover was born in Haifa, Israel in 1947. He is currently a Distinguished Research Professor in the Faculty of Medicine of the Technion-Israel Institute of Technology in Haifa, Israel. He received his M.Sc. (1971) and M.D. (1975) from the Hebrew University in Jerusalem, Israel, and his D.Sc. (1982) from the Technion. There, as a graduate student with Dr. Avram Hershko and in collaboration with Dr. Irwin A. Rose from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, USA, they discovered that covalent attachment of ubiquitin to the target protein substrate signals it for degradation.
As a post doctoral fellow with Dr. Harvey Lodish at the M.I.T., he continued his studies on the ubiquitin system and made additional important discoveries. Along the years it has become clear that ubiquitin-mediated proteolysis plays major roles in numerous cellular processes, and aberrations in the system underlie the mechanisms of many diseases, among them certain malignancies and neurodegenerative disorders. These studies resulted later in the development of a novel and successful anti-cancer drug, and many more are in the pipeline.
Among the many prizes that Dr. Ciechanover received are the 2000 Albert Lasker Award for Basic Medical Research, the 2003 Israel Prize in Biology and the 2004 Nobel Prize in Chemistry. Among the many esteemed bodies, Dr. Ciechanover is a member of the Israeli National Academy of Sciences and Humanities, the Pontifical Academy of Sciences (Vatican), the American Academy of Arts and Sciences (Foreign Fellow), the National Academy of Sciences of the USA (Foreign Associate), and the Institute of Medicine of the USA National Academies (Foreign Fellow).
|
