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    A Discussion With George Church On His New Book Regenesis And Synthetic Biology
    By Randall Mayes | November 4th 2012 11:32 AM | 11 comments | Print | E-mail | Track Comments
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    Randall Mayes is a policy analyst specializing in biotechnology. His areas of expertise include technology based economic development and public...

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    In a conversation at an expo at Duke University last week, an executive with Oracle and I discussed my new project on sustainability and synthetic biology. He curiously asked if I made monsters. Honestly, I was not aware that profession even existed.

    Clearly, there is a need for more education on this emerging technology. Books on synthetic biology are rare which is unfortunate. In order to fill that void, scientists and writers are providing the needed discussions to supplement the existing highly technical articles. In Rob Carlson’s Biology is Technology (2010), he argues biology has long been a technology. In Revolutions, released earlier this year, based on philosophical and historical discussions I argue that synthetic biology is the logical extension of genomics.

    So, why is synthetic biology important? Many scientists believe an influenza pandemic is impending. The U. S. has an astronomical federal deficit and developing countries with fast growing populations have pollution and a carbon footprint to match. We have volatile energy markets and limited natural resources. These all provide concerns for future generations. Although climate change is inevitable based on historical precedent, in order to address the current social conditions and challenges policy makers are sorting through potential short term and long term solutions to these challenges as well as new sources of economic development.

    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.

    For me, reading Regenesis raised several questions. In order to better understand the barriers scientists face in their research, I posed these questions to George.

    Your Career

    I vaguely recall you lurking around the zoology labs in the old biology building at Duke University where I was a graduate student, but more in field biology. I eventually became a policy analyst specializing in science and technology issues. You on the other hand in addition to being a pioneer in sequencing technology and personalized genomics, your labs have developed multiplex automated genome engineering (MAGE) which will enable researchers to perform genetic engineering at a mass scale bringing these possibilities closer to reality.

    Q:  How did you end up in genomics? 

    A: Searching for a confluence of computing and biology, I found this in crystallography and its application to solving the first RNA fold in Fall 1973 with Sung-Kim at Duke -- during which I typed in all known RNA sequences and wrote software to predict their 3D structures.  Noting that what we had (i.e. automation and computational modeling) was needed in the rest of biology, I switched to Harvard in 1977 to develop molecular multiplexing concepts and began applying them to genomes, proteomes, transcriptomes and other omes. In that year I also worked on the first broadly used plasmid vector (still in use today) pre-saging synbio systems and chassis projects.

    Sustainability

    Synthetic biology will lead to novel, biodegradable building materials and plastics, and even bioengineered houses in a desired shape supported by scaffolds and grown from seeds. You reference  www.inhabitat.com/grow-your-own-treehouse. If this example does not amaze readers, Rachael Armstrong’s work on this topic http://ieet.org/index.php/IEET/bio/armstrong  and especially http://ieet.org/index.php/IEET/more/armstrong20120704 certainly will. 

    Q:  One of the topics in my current project looks at synthetic fuel as a supply side solution to sustainability. When I attend energy talks, inevitably a pie chart with the forecasts for 2020 and the percentage of each energy source emerges. Your discussion of Virgin Airlines use of biofuels is fascinating. Jay Keasling, Craig Venter, you, and others are also working on synthetic biofuels; however, these are not in the forecasts. Windmills get more respect than synthetic biology. Why do you think that is?

    A:  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  goo.gl/9Z1t0

    Evolution

    You discuss the possibility of resurrecting extinct species, dinosaurs, and even Neanderthals. 

    Q: But, what about factors relating to developmental biology? Given that we know the genetic codes of these species; what about epigenetics, microRNAs, and developmental pathways that help make up the phenome? How can bioengineers replicate these components?

    A: Many of these 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.

    Diseases

    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 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.

    Thermodynamics and Entropy

    Q: What does the curious reader need to know about thermodynamics, entropy, and Harold Morowitz’s work at George Mason University as it relates to developing the field? 

    A: I make the argument that a shift from unrigorous qualitative description to quantitative measurements accompany each industrial revolution – e.g. time for agricultural revolution, length for civil engineering, thermodynamic entropy and temperature for the steam revolution, etc.  The current revolution in computing and life, includes measures of information and replication. Harold Morowitz’s writing inspired me as a teenager to think about (and to work on Mycoplasma) minimal cells as complex, yet comprehensible and hence engineerable.  Harold has had similar influence on Tom Knight and Clyde Hutchison (and hence the whole JCVI).  How crucial will such minimal cells be? Is the transition from non-life to life qualitiative or quantitative? Read Regenesis.

    Comments

    car2nwallaby
    Sounds like an interesting book.  Of course, this doesn't mention how hard synthetic biology is to get to work as you expect, or how much we still don't know.  Thanks for the interview though.
    randallmayes
    I just read your bio and it sounds like we have similar interests. Yes biology is extremely complex, but all of the names mentioned in the article have provided proofs of concept and we are closing in on novel products and vaccines. I agree with George, a Schumpeterian revolution is looming.
    Randall Mayes
    car2nwallaby
    Definitely!  Perhaps it just seems harder from the trenches than for the generals :-)
    MikeCrow
    Synthetic biology is one of the pathways to full scale Nanotech. We can already pretty much code any sequence we want, and we're getting the tools to analyze what our sequence will make, so it's only a matter of time. And this revolution will make the others look pedestrian.
    Never is a long time.
    randallmayes
    I discussed this topic with Drew Endy, and he does not think of symbio as seperate from nanotechnology. What I have learned from George and Rob Carlson's book is that where bioengineering needs to advance is in the interplay between theoretical and experimental biology. This is where the new tools and quantititative measurements will take biology to a real engineering discipline.
    Randall Mayes
    MikeCrow
    I started reading Drexler in 86 or so, and I've watched the enabling tech develop. So Yes, I can see why Drew said that. We still need nature to guide our hands, but it won't be long until we can take the training wheels off.
    Never is a long time.
    randallmayes
    Unlike my father, I'm not a physicist but from what I understand about nanoscience and physics is that things are more constant and predictable. So, in biology you have to perturb the system to understand the redundancy and complexity.
    Randall Mayes
    MikeCrow
    In part (I think) synthetic biology will help this a lot, what Venter's team did was to remove a lot of what might be redundancy, and will give a better chance(tools?) of understanding the complexity.
    Never is a long time.
    randallmayes
    Then, after you gut the genome and start adding new components, you have to evaluate the noise or crosstalk with other components. In nature, insulating factors prevent this.
    Randall Mayes
    MikeCrow
    Exciting times!

    But I think to your point, I think this ought to keep our ambitions low when dealing with radical changes that still use existing cell dna/functions.
    Where I think, if all you're doing is trying to assemble a couple specific molecules and you can chuck most of the unknown cell code and concentrate on assembling your molecules.

    I've been waiting on the "universal" Nano-Assemblier for a long time :)
    Which always makes me think about how most of the Wizardry shown in the movies could all be based on advanced nanotech.
    Never is a long time.
    randallmayes
    I think this ought to keep our ambitions low when dealing with radical changes that still use existing cell dna/functions.
    Do you think we can reverse engineer what occurs in nature ( if it is a radical change)?
    Randall Mayes