A miniconference, but still a step in the right direction. “The aim of this research group is to create theory and experiments to produce at least one, or several, candidate evolving protocells in the next decade.”
While physicists at CERN currently study the origin of the universe and the origin of matter, in the future they may be asked to help crack the origin of life too. On May 20, a small group of chemists and biologists gathered at CERN for a brainstorming workshop discussing ideas about the origin of life, and to hear from CERN experts about how to organize a scientific community from disparate research groups and how to access powerful computational resources.
“There is a serious risk that the answer to the question ‘How on Earth has life appeared on Earth?’ will mainly remain in the realm of philosophy for the years to come unless we can take definitive scientific approaches,” said Stuart Kauffman, an American molecular biologist and complexity theorist who co-organized the workshop with Markus Nordberg, resources coordinator at ATLAS, one of the largest experiments at CERN.Kauffman and his colleagues believe that the crucial step towards life was the formation of autocatalytic sets. An autocatalytic set is a group of molecules which undergo chemical reactions in which some of the molecules catalyze - that is, significantly increase the rate at which the reaction takes place - other reactions in the set. Importantly, though, all molecules mutually catalyze each other’s creation, meaning that autocatalytic sets are ‘self-sustaining’. It’s thought that molecular reproduction and protocells then emerge from such a system.
The text in Cern: called together by Ignatios Antoniadis/PH-TH & Markus Nordberg/PH-ADO.
Work on the Origin of Life is poised to converge onto a fourth phase and, many of us hope, success.
The first phase concerned prebiotic synthesis of the small molecules, amino acids, nucleotides, lipids and others, essential for life and spanned some forty years.
The second overlapping phase was inspired by the symmetric of the DNA or RNA double helix, presumed that life must necessarily be based on some form of template replication of one strand by ligation of free nucleotides to create the second strand, melting of the two strands and cycling again. Spearheaded by L. Orgel, but with many others, this effort has, to date, failed.
The third phase begins with the discovery that RNA molecules can act as enzymes, and posited the RNA world, in which RNA molecules dominated. This has led to slightly successful efforts to evolve an RNA sequence able to template replicate itself. Current success is an evolved ribozyme able to do so for 14 nucleotides.
The forth phase is converging around four ideas: 1) liposomes, hollow bilipid spheres obtainable from lipids in water, can grow and divide. We now widely hope that these can serve as “containers” bounding proto-cells. 2) Sources of free energy, from pyrophosphate to proton pumps. 3) A minimal metabolism in a “messy” systems chemistry which supplies the small amino acids, nucleotides and lipids for proto -life. 4) Collectively autocatalytic sets of polymers, peptides, RNA, or other, which achieve molecular reproduction in dividing liposome containers, hence also open ended evolution. At present, a 9 peptide collectively autocatalytic set has been constructend, achieving catalytic closure, and demonstrated beyond doubt that the DNA or RNA double helix is not needed for molecular reproduction. In addition a two membered DNA autocatalytic set has been constructed and two two membered RNA ribozyme autocatalytic sets have been selected from a large RNA library.
The author, in 1971 and 1986 proposed a theory in which the emergence of collectively autocatalytic sets is a first order phase transition as the diversity of polymers that are also candidates to catalyse the reactions they undergo, increases in diversity. Recent theorems have improved upon this initial model, simulations have shown that small collectively autocatalytic sets can emerge in this process and grow together, and also that, in the presence of inhibition of catalysis and if contained in duplicating containers, can indeed serve as plausible protocells able to evolve indefinitely.
The author has gathered some 17 scientists from around the world to collaborate and compete with one another, CERN/LHC experiments style, in a generative scientific environment.
Kauffmans talk (bad quality, webcam only):
"The current status of work on the origin of life"
“For a long time, it has been debated how likely it is that such autocatalytic sets exist in arbitrary chemical reaction systems,” said Wim Hordijk, a computational and bioinformatics specialist at the University of Lausanne in Switzerland.
“If I randomly throw a bunch of molecules together, and let them react according to the possible reactions between them, can I expect to see one or more of these autocatalytic sets? Some researchers believe they are very likely to occur. Others believe that it is almost impossible that they appear in a random chemistry – similar, they sometimes argue, to the question of what the probability is that a whirlwind blowing through a scrap yard will put together a Boeing 747,” Hordijk said.
Analyzing autocatalytic sets
Until now, little mathematical analysis has been done on this question. But recently, Hordijk developed computer models to explore possibilities and scenarios for autocatalytic sets, in the hope that it could help others figure out how to set up laboratory experiments that would otherwise be too expensive and time-consuming without this prior knowledge.
“So far we have used our own personal computers or relatively small computer cluster to run our simulations on. However, we have already run into limitations in terms of available computing power,” Hordijk said.
Hordijk and his colleague Mike Steel have developed a model of a chemical reaction system where the probability of an arbitrary molecule being a catalyst for an arbitrary reaction was two in a million, a probability that is “chemically plausible” he said. Running this model on the LHC computing grid, he found that, with this level of catalysis, a set of about 65,000 different molecule types or more will have a high probability of forming an autocatalytic set. This is actually reasonable for a chemist in a laboratory to test, he said.
“We are hoping to use the computing grid to perform [future] simulations and analyses, which would enable us to go much further and deeper than we have been able to do so far. We have already done some small test runs just to make sure our software runs on the LHC grid [facilitated by the ATLAS experiment], which seems to be the case,” Hordijk happily reported.Other areas being explored include self-reproducing RNA, ‘metabolism first’ theories and self-reproducing liposomes - small vesicles formed when lipid molecules, like fats and oils, align to make a membrane. Almost all the theoretical work is underpinned by complex models that would need large-scale computing power.
There are several options for computing power available out there, Bob Jones, project director of CERN’s openlab told the group, including other grid infrastructures, supercomputers, clouds and volunteer computing.
“New science can arise in unexpected ways”
"Our group of seven origin of life workers, representing an initial group of 22 of the top researchers in the field, were truly thrilled by our CERN meeting,” said Kauffman. “If CERN wishes it, we hope to become a small part of the CERN world, for the origin of life is itself a problem in physics. New science can arise in unexpected ways."
First, however, the Origin of Life group needs to make a formal proposal for such a project, and CERN must agree formally to support the work. “We hope this occurs. Such approval will help drive an international effort in origin of life research,” Kauffman said.
So, no results from here in several years.