ISSOL ’05 Beijing
14th International Conference on the Origin of Life
UREY-MEDAL PRESENTATION SPEECH
(June 23th, 2005)
“In a world where it is so easy to neglect, deny, corrupt and suppress the truth, the scientist may find his discipline severe. For him the truth is so seldom the sudden light that shows new order and beauty; more often, truth is the uncharted rock that sinks his ship in the dark”.
These seem to be rather solemn, if not gloomy opening words for a Urey-medal presentation which – according to a longstanding tradition of ISSOL –is suppos-ed to be a speech on the sunny, if not funny side. I hasten to add that these grand and noble words about truth are not my own; they are a excerpts of a banquet speech the Australian-British organic chemist Sir John Warcup Cornforth gave when he received – together with Vlado Prelog – the Nobel prize for Chemistry 1975 for his pioneering work on the stereochemistry of enzymic reactions.
It is not so uncommon that chemists and biologists in their later years after hav-ing spent their most active years studying nature at the interface of chemistry and biology become interested in the problem that focuses on the most intimate contact point in that interface, the problem of life`s origin. So did Cornforth, however, without suscribing as ISSOL-ian. As an unchallenged authority in matters of molecular chirality in biological systems, he once gave a lecture which, in turn, was published in a not too well known but appealingly named journal (“Interdisciplinary Science Reviews” vol. 9, 107-112, 1984) and in which he summarized his views on the potential role of chirality in the context of life’s origin, on minimal conditions for a non-biotic emergence of homochiral self-replicating species from racemic precursors, and on the importance of the interplay of synthesis and hydrolytic decay for the evolution of replicators. Re-cently, he came across an exposition of some of my own work and, in this con-nection, he wrote me a short and provoking e-mail saying: “Albert, what is your most recent definition of life?” I replied in a rather sinous and twisted way, pointing to the complexity of the question and the pitfalls of such definitions. Cornforth reacted quickly by another e-mail which culminated in the refreshing statement:
“A system is alive, or has life, if it resists inevitable decay by exact self-replicat-ion and can evolve by occasional inexact replication”.
Now, I must tell you that Cornforth, who at the age of 88 is alive and well as a professor emeritus of the University of Sussex in England, devoid of the capa-city of hearing since his early youth, is a man extraordinary in many ways. One of them is his reputation, among all who know him, to be contemporary Organic Chemistry’s leading inventor of limericks. And so I challenged him by pointing out that his definition might be worthy of being expressed in limerick form. And now it just so happens that I have the privilege to inaugurate in public and in front of just the right audience Cornforths's most recent limerick creation, dating February 19th 2005:
“You rot all the time you're alive,
And copy yourself to survive.
A copy untrue
May work better than you.
If it does, you can die; it will thrive.”
By both its content and eloquence, this captivating and enlightening limerick is a fitting bridge to the very person this presentation speech is about: ISSOL’s Urey medalist 2005. ISSOL-tradition forbids to mention his or her name at once. I may say that he or she too is, a proficient writer, like Cornforth, though prefer-ably in prose; he or she too – in fact, it happens to be a he – has expressed thoughts on how contemporary science might react to the ongoing challenge of articulating as compactly as possible what the material essence of life is suppos-ed to be, and finally, he too belongs to the brand of scientists who are rigorous empirists and, at the same time, driven by a platonic desire to go for the funda-mentals, scientists who do not loose sight of the forest while barking up trees. It is not inconceivable that he, our awardee, whose biological roots are in Northern as well as Southern Europe, has inherited via Lamarckian channels elements of his characteristic mix of Anglo-American empiricism and Latin-type abstract-ionism from his PhD-advisor, a man who himself is a unique hybrid between a rigorous empirist and great theorist and, moreover, a teacher well known for leaving rather strong and lasting imprints on his students.
“Tristo è quel discepolo che non avanza il maestro” – “It's a poor pupil who will not excel the master” (Leonardo Da Vinci). Our awardee did indeed excel his master, his PhD-supervisor, and with time progressing, he did so more and more, after all, the two continue to co-operate in the same field, still up today, once a week, they play tennis together. To excel the master in science, however, and specifically that master, must be a tough perspective indeed. Happily, our awardee was strong as well as wise enough to escape the dilemma by moving in his science fearlessly ahead into the promised land that is “flowing with milk and honey” (Exodus ch. 3 v.8), the land that Moses, the master, could see from far away, but was not allowed to enter himself. The land I mean is the land of in-vitro evolution of catalytic function, a land where principles and tools of bio-logy give birth to new chemistry, a land into which to enter and start cultivat-ing, our awardee was one of the first. He became one of the land’s pioneers.
In any of the fields of human activity that challenge human creativity – be it pure thought, art, science or technology – to become, and to succeed as, a pio-neer is one of the highest forms of achievement; we might say “pioneers are the catalysts of our cultural evolution”. I am not unaware of the fact that this pro-nouncement, in principle, is double-edged since, after all, much depends on what is pioneered. Yet, this happy occasion of an ISSOL conference banquet is not the place to look at shadows, we are here to rejoice in honoring a pioneer in science, a pioneer in the development of a tool to acquire new knowledge, a pathfinder in the creation of a new and powerful way to induce discoveries in the realm of molecules
In-vitro evolution of populations of macromolecules toward the emergence of pragmatic catalytic activity is research at the very heart of what ISSOL, as a community of researchers, can aspire to, namely, to conceive of, and to experi-mentally exemplify the range of principles, properties and processes that to-gether may add up to Nature`s potential to have become alive. The principle of the evolution of replicable macro-molecules by mutation, selection and ampli-fication, the great dream behind Manfred Eigen’s pioneering theoretical analysis of some 30 years ago, has – in modernized form – descended to reality and practicality in the experiments and achievements of our awardee, who fearlessly has described the aims of his work by the proud words: “Our research aims to recapitulate the biochemistry of the RNA-world in the laboratory. We use in-vitro evolution to explore the catalytic potential of RNA, especially to search for RNA enzymes that have the ability to catalyze their own replication”. Proud he can be indeed of his and his collaborator`s achievements along these lines: the discovery, by in-vitro evolution, of RNA-enzymes that specifically cleave single-stranded DNA; the creation, again by in-vitro evolution, of the very first DNA-enzyme, one that catalyzes a metal-ion dependent cleavage of RNA. This landmark discovery, along with related findings that followed, profoundly in-fluenced our views on what we might expect with regard to the distribution of catalytic potential within the landscape of macromolecule families. Another break into the narrowness of our views, one in a reverse direction in as far the minimal structural complexity of ribozymes required for catalytic activity to occur is concerned, was our awardee’s systematic search for, and discovery of, a RNA ligase ribozyme composed of only two different nucleobases; a remarkable and important insight in our attempts to understand why biomolecules have the structure they have. On the methodological side, speeding up the selection-amplification-mutation cycle of in-vitro evolution must have always been a challenge for its practioners. Our awardee`s answer to this quest was yet another pioneering development, described for the first time in a paper with the proud title: “Continuous in-Vitro Evolution of Catalytic Function”. There it is shown how the in-vitro evolution of an RNA ligase ribozyme can be accelerated so that you can go through hundreds of generations a day. What a feat, and what a prospect!
I suspect by now that the research-fingerprint of an ISSOL-ian that I have given you thus far already over-determines the candidate’s identity, so that I suppose that most of you have clearly identified him and can hardly wait to applaud and congratulate him. And so I have the pleasure and the privilege to present to you a man of extaordinary brilliance in science and elsewhere: Gerald Francis Joyce.
Albert Eschenmoser
