Some times two men can vehemently disagree, and both be right and wrong, at the same time.
I think one of the final questions Dave and Tour debated was whether researchers had achieved complete self-replication with a ribozyme, with Dave saying yes (and referencing Joyce 2002 as an early example) while Tour vehemently denying it was able to fully self-replicate.
Here I think they were genuinely talking past each other.
The system referenced in Joyce 2002 is able to fully self-replicate, but not in the manner I assume Tour was thinking about.
Paul & Joyce 2002:
That ribozyme really is able to fully self-replicate from appropriate substrates. But it’s a ligase ribozyme that assembles new copies of itself from some rather large and complex substrates (basically 2 large fragments of itself) by basically just ligating them together. That does qualify for the definition of self-replication, and it is a ribozyme.
I’m not claiming to be able to Tour´s mind, but I’m trying to steelman Tour here and give a possible explanation for why he would insist ribozymal self-replication has not been achieved in the face of research really showing that it has. He did give a clue what he might have been thinking about when he started speaking about what “percentage” has been replicated.
I think Tour took Dave to be speaking about something akin to the “holy grail” of RNA world research, which is a generalist RNA-dependent RNA-polymerase ribozyme, that can fully copy it’s own sequence from an unfolded template, in addition to also being able to make complementary copies of other templates. Not a ligase ribozyme, but a universal generalist polymerase ribozyme that can use it’s own unfolded sequence as a template to polymerize a new one. Such a ribozyme has not been found yet, though Joyce and co-workers are actually close to achieving that.
My bold:
Abstract
An RNA polymerase ribozyme that has been the subject of extensive directed evolution efforts has attained the ability to synthesize complex functional RNAs, including a full-length copy of its own evolutionary ancestor. During the course of evolution, the catalytic core of the ribozyme has undergone a major structural rearrangement, resulting in a novel tertiary structural element that lies in close proximity to the active site. Through a combination of site-directed mutagenesis, structural probing, and deep sequencing analysis, the trajectory of evolution was seen to involve the progressive stabilization of the new structure, which provides the basis for improved catalytic activity of the ribozyme. Multiple paths to the new structure were explored by the evolving population, converging upon a common solution. Tertiary structural remodeling of RNA is known to occur in nature, as evidenced by the phylogenetic analysis of extant organisms, but this type of structural innovation had not previously been observed in an experimental setting. Despite prior speculation that the catalytic core of the ribozyme had become trapped in a narrow local fitness optimum, the evolving population has broken through to a new fitness locale, raising the possibility that further improvement of polymerase activity may be achievable.
Very close, but not quite there yet. It is a generalist polymerase ribozyme, but it can’t yet fully generate a copy of itself by using an unfolded copy of itself as a template. Both men were right about what they were saying, they were just talking about two very different systems and modes of self-replication.