Life in a time of synthetic biology.

The age of synthetic biology may be upon us. The ability to construct novel biological pathways that do not naturally exist; the design of new life forms driven for the first time not by natural evolution but by actively interrogating the very molecules and atoms that create life. Something, however, fundamentally limits this next singularity, we as scientists still do not understand how nature achieves a crucial component of the central dogma of molecular biology-Protein Folding.

The conversion of the primary sequence of amino acids into a complete functional biological machine still remains enigmatic since Cyrus Levinthal proposed the so-called Levinthal's paradox of protein folding over 50 years ago. Much, indeed, has been done since then but the challenge still persists. The challenge is, of course, to successfully achieve protein macro molecular assembly with the same predictive precision as micro particle behavior using quantum mechanics. Levinthal's paradox is of course a kinetic problem and ideas such as protein folding funnels derived from energy landscape theory have been employed to explain this paradox. Ultimately, our struggle remains not so much the kinetics but the thermodynamics of folding. In a sea of numerous possible conformations how do we know which conformation is the right one? Do we even know what structures exist just by analyzing an amino acid chain?

Most of the predictive tools at our disposal have been "homology based" which means we have had to rely on observing nature "in action" and only then "predict" by comparing with natures results. This does not sit well with me because if there is one thing we know for certain is that nature's rules are in a constant state of flux, forever changing. It is perhaps unreasonable to expect the chemistry of life to conform to a particular pattern- after all, life is by definition variable. Perhaps a quantum mechanical description of "static and predictive behavior" is in contrast to Charles Darwin's theory of Biological Evolution. Still this does not stop us from trying, so we assemble genetic parts like mechanical engineers in a Ford factory; we design genetic circuits like Silicon Valley engineers writing code for the next big thing (In the truest sense, this is the next big thing). My Molecular Biology training has, however, taught me to never treat biochemistry like mechanical engineering because the very driving force of life is variation.

So what will life look like once the "mastery" of matter is achieved? once variation is incorporated into the fabric of genetic engineering, once we accept that a bacterial factory is not the same as a Ford or Tesla factory. The possibilities are endless and I am excited to see that time, dawn is definitely approaching. Computation is being refined with improved statistical thermodynamics and refined biological models. Enzymes are also being created without heavy reliance on copying nature's answer sheet. Exciting times are definitely ahead but as always I remain a student of the universe and all that is in it.