George Church, his new Book Regenesis And Synthetic Biology

Science 2.0 – In October, Basic Books released Regenesis by Harvard Medical School Geneticist George Church and science writer Ed Regis. Their successful collaboration interestingly resulted from the pair having the same literary agent. In Regenesis the authors ask, “What should we do?” How can we balance economic growth and a sustainable environment? How can we outsmart viruses? In an attempt to answer these questions, Church and Regis argue that synthetic biology is an industrial revolution with the potential to change life as we know it and discuss its possibilities. Among these exciting possibilities are creating novel materials and biofuels, and providing a better understanding of evolution and complex diseases leading to new drugs and vaccines.

Synthetic Biofuels

Many revolutions look irrelevant just before they change everything (swiftly). For example the WWW went from zero to millions of web pages in one year (1993). Cyanobacteria are about 100X more efficient than the corn-to-ethanol that many knew from the start was simply lobbying, not smart bioengineering. Cyanobacterial biofuels are now closing in on $1.28 per gallon.

Joule (synthetic fuel startup) claims an $1.28 (unsubsidized) all-in cost for Joule fuels. That includes both capital and operating costs, 70/30 debt equity, 15 year depreciation, and reasonable interest rates. They have taken huge strides toward full commercialization. We also note the scale – 25,000 acres at 25,000 per gallon – 625 million gallons per site (potential).

Joule continues to move out of stealth and into the light with its transformative Sunflow-E and Sunflow-D fuels, made biologically from waste CO2, sunlight and saline water with no intervening biomass step.

Audi selected Joule as its exclusive partner in the development of biologically-derived diesel and ethanol, after extensive evaluations of Joule’s proprietary technology and commercial plans. The relationship will help spur production of Joule Sunflow-E and Sunflow-D, including fuel testing and validation, lifecycle analysis and support for Joule’s SunSprings demonstration facility located in Hobbs, New Mexico, which began operations this month.

Epigenetics

Many epigenetic components self-assemble under the guidance of the genome (imbedded in a highly related cytopasm). We are also getting quite good at manipulating the epigenetics directly by introducing regulatory factors– for example the 4 factors needed to change adult skin fibroblasts into embryo-like stem cells. Both strategies are improving rapidly now.

Going Beyond what Nature can do to defeat all viruses

For diseases, Duke’s Jingdong Tian’s lab recently created a 3D printer that can print out DNA using wells and layering. Possibly tissues and organs are next, which is very exciting.

Your discussion on transhumanism (H+) or extended life span by protection from viruses, TB, rabies, prions, skin cancer from UV rays, and protection from Van Allen Belt radiation in future space flights through reprogramming DNA sounds equally promising. You talk about changing the cellular machinery that reads and expresses the viral genome in hosts, but also reprogramming viruses.

Q: How does this work? How can we possibly reprogram all viral genomes? Is the work on our own genomes similar to Geron’s work with telomerase therapy which is in clinical trials to provide DNA repair to overcome naturally occurring telomere shortening?

A: In contrast to cells which share a core set of genes, viruses share very little, except for their dependence on those cellular core factors. These factors represent the nearly universal genetic code for translating mRNAs into proteins. We take advantage of the “redundancy” of this code (i.e. 64 codons for 20 amino acids) to change the host genome without changing its proteome at all. This requires so many accommodations (via computer) that no virus could mutate all at once sufficiently to accommodate the new code rules. We have made huge progress toward getting this to work in the key industrial microbe, E.coli.

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