When you first meet Aaron Ciechanover, he appears to have the distracted air of a man who feels slightly inconvenienced to be in whatever situation has been apparently imposed on him. But this preoccupied demeanor belies a mind which is ready to hold forth on a disparate variety of topics with infinite verve and enthusiasm and which is not reluctant to be politically incorrect, provocative and utterly honest. And it hides a broad smile which is very readily revealed at the mention of a favourite incident or fact.
If there is one word to describe the Israeli doctor, biochemist and Nobel Laureate it’s passion, and this passion is pronounced no matter what the topic of discussion; from protein degradation to languages and traveling, from politics to history. Whether we were talking about protein structure or Israel-Palestine relations, Ciechanover’s thoughts were always opinionated, honest, cogent, provocative and without a dull shade in them. This is the kind of stimulating person that you always want as a dinner companion.
I met Ciechanover along with a small group of students for dinner at a charming restaurant on a path lined with cobblestones somewhere close to Lindau’s Inselhalle on Fischergasse street. As we shuffled around our tables to accommodate everyone, Ciechanover was joined across the room by his fellow Nobel Laureate and friend Peter Agre, whom we met earlier. Both Agre and Ciechanover joke that they are doctors who received the Nobel Prize for chemistry without having any reasonably good knowledge of chemistry. But the humor hides an aspect of chemistry that we have been emphasizing here for a while now; its extraordinary diversity and synergy with other fields that allows even people who may not be trained as chemists to make contributions to the subject.
Aaron Ciechanover shared the Nobel Prize for chemistry for one of those discoveries that are deep and long-lasting. As a rule the Nobel Prize is awarded to great discoveries and not great scientists. The greatness of all discoveries is naturally not alike. The discovery that Ciechanover made ranks among those great discoveries that are fundamental for understanding life. The reason why DNA or electron transport in biological systems or the genetic code are considered prize-winning discoveries are not only because they demonstrated something absolutely basic about living systems but because they are absolutely universal. DNA is the molecular basis of all of life. The genetic code similarly underpins every single organism’s existence on our planet. Aaron Ciechanover’s and others’ discovery of ubiquitin-mediated protein degradation is similarly universal and constitutes the basic mechanism of protein waste elimination in all eukaryotes. This is as fundamental as you can expect a process to be. Until Ciechanover and his colleagues discovered this, protein degradation was considered to be a general and non-specific process that was of secondary importance to the main processes of life. But Ciechanover and his colleagues Avram Hershko and Irwin Rose discovered ubiquitin, a small protein that as the name indicates is ubiquitous in eukaryotes and crucially aids in the destruction of proteins which have outlived their utility in one way or the other.
Naturally Ciechanover likes talking about the story of how he heard about the prize. Ciechanover was getting into his car to go somewhere when his son came to tell him that somebody from Stockholm had left a message and asked to call him back. Since Ciechanover has many colleagues and friends in Stockholm, he assumed that it must be one of them and decided to wait until later to call back. It was when he returned after a few hours and called this person with the unfamiliar name that he heard about the news. Amusingly, it was just 5 mins before the official prize announcement and the Stockholm official who delivered the news had to hang up right away. While all this was happening Ciechanover’s co-laureate Hershko had gone for a swim and had no mobile phone. The swimming suit clad Hershko was surprised to see a troupe of journalists and others gathered in front of his house when he returned after a couple of hours and wondered what was happening.
Ciechanover’s love of storytelling extends to his own interests which involve reading biographies and history books as well as a medieval romance set in 17th century Italy. I was delighted to hear him mention Max Perutz’s absolutely delightful collection of essays, “I wish I’d made you angry earlier” which I have read several times as one of his favorites. He also mentioned Harold Varmus’s recent memoir; Varmus is one of President Barack Obama’s chief science advisors.
The students gathered around the table constituted a diverse and eager lot. They included students from Norway, Sweden and Russia. They were researchers in diverse fields, from gene therapy to thermodynamics to astrophysics and all exhibited a love of science, traveling, languages and culture. All of them greatly appreciated the connection with students from other countries that the Lindau meetings provide. All of them were highly motivated and seemed to latch on to every word that Ciechanover was saying. Ciechanover in turn had a very lively interaction with the students and he answered their questions with gusto and emphatic consideration. I also briefly and productively talked to him about the clinical aspects of ubiquitin from a drug discovery viewpoint. There are some efforts underway to discover small molecule inhibitors of the protein, but considering its ubiquitous distribution in the body the target may not exactly be druggable. However if not anything else, small molecules can at least serve as probes to investigate basic functions of the protein.
Ciechanover also emphasized the importance of liking what you do. In this he reiterated what Peter Agre had noted during his interview; that until you take risks and do what you like, there is no way to know whether you have succeeded or failed. You can take the safe road and settle for a safe life, but then you potentially miss out on doing something exceptional. Even if you don’t do something exceptional you can still take pleasure in the process of learning and doing. That is the sheer, unadulterated joy of science. Ciechanover also reminisced about flip-flopping a little during his career since he enjoyed both treating patients and doing lab research. But he said he learnt a lot from both. Ciechanover also mentioned that one of the joys of scientific research is the joy of meeting old friends and researchers several times every year in interesting places around the world.
During the long, enjoyable and ambrosial dinner which included the local Lake Constance speciality catch Felchen and was followed by a succulent dessert of fruit and ice cream, Peter Agre kept on coming to our table to take good natured jabs at his friend and colleague. At one point he announced that he knows even less chemistry than Ciechanover. Perhaps the most amusing moment was when he offered to sing Tom Lehrer’s delectable song about the elements. With a flourish, Agre launched into an almost perfect rendition of the piece. I have heard the song several times and yet cannot sing even the first stanza; Agre must have practiced the song quite well. Friend of Ciechanover that he was, Agre announced that the name of an unstable element that was not included in the song was ‘Ciechanoverium’.
All in all, we had a wonderful time and a really enjoyable dinner with a man who did not mince his words and who provided us with a lot of instruction, information and infinite enthusiasm.
Peter Agre and Aaron Ciechanover
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