Thank you for that, it deserves an award for the most useful first post ever.
So, as a non-biologist who just has a layman’s knowledge of these things, the idea of reconstructing an organism from nothing but its DNA would be like reconstructing a car engine from the crankshaft? The causal chains that make an engine go all pass through the crankshaft: it moves the pistons up and down, drives the fuel pump to bring petrol to the cylinders, drives the camshafts that open and close the valves at the right time, and receives the energy of the power stroke and passes it to the transmission. So obviously the crankshaft is how the whole thing works, and complete knowledge of the crankshaft must in principle let us reconstruct the whole engine.
(I am indebted to my colleague William Powers for the crankshaft as an illustration of how to misunderstand cyclic causal chains.)
It is worth noting that you can bootstrap a genome with non-DNA machinery which is good enough, and get it to work and eventually equilibrate as it makes its own native machinery. That’s how Craig Venter and company ‘created’ their ‘artificial’ bacterium a while back—they chemically synthesized a near-exact copy of one of the smallest and simplest known bacterial genomes (no small feat by the way, chemical synthesis of DNA is expensive and error-prone during the assembly steps of smaller pieces into the full chromosome) with a few watermarks to show it was theirs, and shoved it into another related bacterial species (again no small feat). They were close enough that that other species’ proteins were able to run that new genome’s genes, getting a causal cycle going, and after a few dozen generations all the old proteins/metabolites/etc had been diluted out and replaced with those made by the artificial genome. This of course basically requires a related living system, on top of something like the basic definition of the genetic code.
The fact that nongenetic information is perpetuated in the form of epigenetic state, physical shape and arrangement, etc adds another loop that many times doesn’t even feed through the genome at all, but rather relies on the genome and the proteins it codes for to set up a landscape of attractors that these factors are capable of occupying and which ones can lead to which others through paths which the cell can stay alive through.
If you could somehow synthesize compatible non-DNA machinery capable of interacting with a particular genome, you might be able to get a cell going—but the question is how do you do that given just the genome and the genetic code to go on, and once you do does the system fall into any of the normal stable attractors, and how much of that organism is things like the double membrane of a gram negative bacterium, passed on from its parents but only its capability for replication really represented by the genome or its products. All membranes come from previously-existing membranes, things like that. Animal cells, with all the fun attractors they fall into from every different cell type to cancer to all of their intercelular interactions are examples of cells that have their history as a vital component of their identity.
Thank you for that, it deserves an award for the most useful first post ever.
So, as a non-biologist who just has a layman’s knowledge of these things, the idea of reconstructing an organism from nothing but its DNA would be like reconstructing a car engine from the crankshaft? The causal chains that make an engine go all pass through the crankshaft: it moves the pistons up and down, drives the fuel pump to bring petrol to the cylinders, drives the camshafts that open and close the valves at the right time, and receives the energy of the power stroke and passes it to the transmission. So obviously the crankshaft is how the whole thing works, and complete knowledge of the crankshaft must in principle let us reconstruct the whole engine.
(I am indebted to my colleague William Powers for the crankshaft as an illustration of how to misunderstand cyclic causal chains.)
Interesting analogy. I like it.
It is worth noting that you can bootstrap a genome with non-DNA machinery which is good enough, and get it to work and eventually equilibrate as it makes its own native machinery. That’s how Craig Venter and company ‘created’ their ‘artificial’ bacterium a while back—they chemically synthesized a near-exact copy of one of the smallest and simplest known bacterial genomes (no small feat by the way, chemical synthesis of DNA is expensive and error-prone during the assembly steps of smaller pieces into the full chromosome) with a few watermarks to show it was theirs, and shoved it into another related bacterial species (again no small feat). They were close enough that that other species’ proteins were able to run that new genome’s genes, getting a causal cycle going, and after a few dozen generations all the old proteins/metabolites/etc had been diluted out and replaced with those made by the artificial genome. This of course basically requires a related living system, on top of something like the basic definition of the genetic code.
The fact that nongenetic information is perpetuated in the form of epigenetic state, physical shape and arrangement, etc adds another loop that many times doesn’t even feed through the genome at all, but rather relies on the genome and the proteins it codes for to set up a landscape of attractors that these factors are capable of occupying and which ones can lead to which others through paths which the cell can stay alive through.
If you could somehow synthesize compatible non-DNA machinery capable of interacting with a particular genome, you might be able to get a cell going—but the question is how do you do that given just the genome and the genetic code to go on, and once you do does the system fall into any of the normal stable attractors, and how much of that organism is things like the double membrane of a gram negative bacterium, passed on from its parents but only its capability for replication really represented by the genome or its products. All membranes come from previously-existing membranes, things like that. Animal cells, with all the fun attractors they fall into from every different cell type to cancer to all of their intercelular interactions are examples of cells that have their history as a vital component of their identity.