The Church of Synthetic Biology

 Alexander Pope once said, “Who builds a church to God and not to fame, will never mark the marble with his name.” When it comes to making a mark in the molecular genetics community, Harvard scientist George Church has already done it. In the acknowledgements of his new, co-authored book, Regenesis, Church tells us that some 400 journalists have interviewed him; that he has written papers with 1,274 other scientists (he might know them all personally because, he also says, his dissertation thanked 258 people); and that he played a key role in creating many biotech start-up companies (his Harvard web page claims 12). Regenesis offers a glimpse, often seen at a gallop, of how today’s scientist-celebrities engage, often simultaneously, in research, self-promotion, and entrepreneurship.In Regensis, Church – abetted by science writer Ed Regis – explains how the practitioners of “synthetic biology will reinvent nature and ourselves.” Note the choice – future tense – of verb. More on this in a minute. Throughout this often meandering and sometimes maddening book, Church and Regis give a personal account of the emergence of synthetic biology (which they define as “the science of selectively altering the genes of organisms to make them do things that they wouldn’t do in their original, natural, untouched state.”) This was once called selective breeding. Later, scientists, journalists, and writers termed it genetic engineering. Now it has a new name, a new wreath of hyperbole, and bold new practitioners with grand designs.The Church of syn bio is a big building with many rooms, all of them bustling with activity. He positively bounds off the pages as a star scientist – an entrepreneur who starts companies, a researcher who has helped author hundreds of papers, and a presence at TED and Davos. He has two personal assistants to manage “one of the most complicated and jam-packed schedules known to humankind.”Regis’s role in this project intrigued me. In the Acknowledgements, Regis says that the collaboration between Church and him was brokered by their agent, John Brockman. Brockman has a long history of publishing books and promoting stories that sit on the “bleeding, screaming thrilling edges” of new technoscience. ((The quote comes from Stewart Brand, one of the people whose blurb for Regenesis graces its dust jacket.)) In the 1970s, he tried to get Gerard O'Neill’s book on space colonies published and later provided writing forums for nanotech pioneer K. Eric Drexler. Regis, meanwhile, has authored two trade books – one dealing with radical technologies of all kinds (1990’s The Great Mambo Chicken and the Transhuman Condition: Science Slightly Over the Edge) and another specifically on nanotech and Drexler (Nano! The True Story of Nanotechnology – the Astonishing New Science that Will Transform the World from 1997).Regis’s earlier writing often had a breathless, “can you believe this stuff I’m telling you?” quality to it. His approach to writing – call it a style or a tic – isn’t often present in Regenesis. But, like renegade bamboo shoots, every so often statements gilded in prolepsis and inevitability punch up throughout the text. The reader is told how synthetic biology will, for example, “blur the distinction between life and nonlife” and will “produce a synthetic, self-replicating, and self-sustaining” cell (my emphases). The disjointed nature of the book also comes, I think, from the union of Regis and Church – the book is chock full of so many lists that I sometimes wondered if Church donated some PowerPoint slides to Regis who then tried to “prose-ify” them.Given Regis’s other books, I found myself asking, Clara Peller-style, all the way through Regenesis: “Where’s the nano?” The original formulation for nanotechnology – or, as it was first called, “molecular engineering” – was deeply rooted in biological thinking. It assumed that researchers’ would master protein engineering to develop novel organic molecules – “protein machines” – which, in turn, would be able to manipulate non-organic  molecules into complex structures. ((A good overview of the relation between biology and nanotechnology is Richard A.L. Jones, Soft Machines: Nanotechnology and Life (London: Oxford University Press, 2008)) This version of nanotech is the precursor, at least in terms of vision, for today’s syn bio. Instead of using genetic engineering to direct the manufacture of novel proteins de novo, the engineers of synthetic biology take standardized biological parts (“BioBricks”) off the shelf, so to speak, and put them together in new ways so as to do some sort of chore. Church & Regis analogize this to electrical engineers taking standard electronic components to configuring them to make a radio or some other device. (“The dream was to do for biology what Intel had done for electronics.”) But, other than a few mentions, yesterday’s nanotech appears largely divorced from today’s syn bio.Given the considerable national investment in bio-nanotechnology, this relation deserves attention along at least two axes. One is in terms of community – how much of the syn bio research community overlaps or self-identifies with nanotech? Another is in terms of public presentation – nanotech (like biotech) arrived on the scene with a considerable amount of hype and speculation. Syn bio is showing up at the party wearing similar duds. Venture capitalists have expressed interest in synthetic biology’s commercial possibilities while non-governmental groups like ETC have prepared reports opposing “extreme genetic engineering” and “syndustry.” In almost every way one looks at it, synthetic biology’s emergence (or “re-identification”) looks strikingly similar to paths that nanotechnology took. ((In March 2011, Luis Campos, now at the University of New Mexico, explored this feature in a great talk at UCSB called “Next Generation Nano? Narratives of Synthetic Biology.”)) Although Syn Bio practitioners might claim “We didn’t even know our field had a history!” its links to molecular biology, electrical engineering, artificial intelligence, nanotechnology, and genetic engineering make it an especially loded vein to mine. ((Luis Campos, “That Was the Synthetic Biology That Was,” in Synthetic Biology:The Technoscience and Its Societal Consequences,  edited by Markus Schmidt  (London: Springer, 2009))  Looking more broadly, syn bio has generated a level of concern and protest rivaling that which accompanied the efflorescence of nanotech as a national research program c. 2000.Both nanotech as well as syn bio should prompt important questions about ethics. Church & Regis admirably alight on these issues but never give an explication that fully satisfies. In one passage, Regenesis discusses how one might use DNA technology to bring extinct species back to the world. Their best example is the mammoth (although they also speculate that one might be able to bring back Neanderthal hominids). They describe scientists’ attempts to capture DNA and freeze it so rare species might one day be rescued. Nowhere, however, do they mention that not having species go extinct in the first place (better conservation, less poaching, etc.) might be a good idea. Of course, it’s not hard to jump from resurrecting the charismatic mega-fauna of the Pleistocene to modifying our own genome so as we live longer. Here, in discussion about immortality and the Singularity, ethical depths are noted but not plumbed.The same goes for history as off-kilter historical analogies are sometimes used. Church & Regis describe how a cloned burcado – a type of mountain goat once found in Spain – died after only living seven minutes. Be not despondent, for the Wright brothers' first flight lasted only 12 seconds…and 66 years later, we were queuing up to see the moon rocks. One is left to presume that in six decades, we might regularly be cloning mountain goats, mammoths, our pets, and ourselves. [followup note - a week after I posted this entry, my colleague David Brock clued me into a post on Gawker in which Church apparently told Der Spiegel that he's ready to clone a Neanderthal, assuming he can find a suitable surrogate...] --  [second follow up note (22 January 2013): in a posting on Forbes.com, writer Alex Knapp points out the various technical reasons why cloning a Neanderthal isn't likely to happen anytime soon] (("Church speaks of having an “extremely adventurous female” give birth to a Neanderthal. But the reality is that success would require dozens of women – many of whom would almost certainly go through the trauma of miscarriage and stillbirths that appear to be inevitable when it comes to cloning. The ethical implications of just this simple aspect of the process are pretty damning."))The history of electronics also appears in some contradictory ways. Church notes several times the exponential progress made in DNA sequencing, likening it to Moore’s eponymous law. At the same time, when discussing the prohibitive cost of algae-derived biofuels, he concludes that only the military could afford these – this ignores the fact that, when they first appeared, transistor-based electronics were also prohibitively expensive. It was the initial purchases by the Pentagon (and the Cold War) that drove the cost down such that consumers could afford by transistor radios.Finally, the end of Regenesis its authors discuss how attempts to ban certain technologies have failed, citing 20’s-era Prohibition as proof that moratoriums don’t work. However, one could argue that the Nuclear Non-Proliferation Treaty hasn’t been a total failure so maybe prohibitions have some merit. The larger problem here is the cherry picking of examples and analogies. Sure, DNA sequencing has followed an exponential path à la Moore’s law. But there are far more examples of technologies that are non-exponential in nature…otherwise, “my car would go 100 miles on a teaspoon of petrol”, etc. etc..Regenesis is best when it gives us insights into the personal worlds of the synthetic biologists. Church, for example, tells of the Personal Genome Project which sequenced the genome of many volunteers – Church, not surprisingly, was the first candidate – so as to publish the information on the Internet. ((Interested readers might like to check out Nathaniel Comfort's new book The Science of Human Perfection on this score.)) We learn a little about the two consent forms Harvard required as well as the IDs of other participants such as cognitive scientist Steven Pinker and Esther Dyson. But what intrigued me most was the membership of this cohort – a molecular geneticist, a cognitive scientist, and an entrepreneur/cyber-libertarian. Maybe I’m fishing here but can we anything deeper from this roster? How were they selected? Was there a PR angle for the choice of people? Church was also involved with start ups that didn’t fly – I mean no disrespect here – and he candidly admits when a venture didn’t work out. But some discussion of why they failed would have gone a long way to tying to help the reader understand not just the science of syn bio but the border between commerce and academia where its researchers and boosters live.A novice would not find Regenesis an easy introduction to molecular genetics. Passages such as “…the anticodon for one of the tRNAs for valine (v) specifically binds to the mRNA codons GUU, GUA, GUG, and the other valine tRNA binds to GUU and GUC (in order to add a valine to the growing protein chain)” had me reaching for my copy of Essential Cell Biology by Alberts et al. (which I’m pretty sure the average owner of this book doesn’t have on their bedside table.). So, as a tool to explain the science of synthetic biology, Church & Regis have some successes but many failures as well.Although it’s nowhere near as revealing as Watson’s account in The Double Helix, Regenesis hints at the competition within the syn bio and genetics communities as egos collide. Church’s treatment of bio-entrepreneur J. Craig Venter, for example, is especially fascinating. (Venter, it should be noted, has also blurbed the book for Amazon). Throughout Regenesis, I thought I detected subtle jabs at Venter. Given their status, visibility, and accomplishments, it’s not surprising that might be some ego friction between the two. Church’s narration of Venter’s 2010 reengineering of the M. mycoides genome so as to include a snippet of text from James Joyce and a misquote from Feynman is great stuff. This gets even richer when Church brags about having once slipped some “synthetic codes” into a plasmid prep line of Venter’s The Institute for Genomic Research (yes, TIGR) as a “youthful prank.” Like many scientists, Church critiques Venter’s claim that his 2010 re-jiggering of the M. mycoides had in fact created “artificial life” or a “synthetic cell.”The real value of Regenesis is as a historical document. Here, c. 2012, we get a picture of how one of the leading players in the field saw his role in the community along with his interpretation of what and who was important. The fact that there are few women in the book as leading scientists is telling as is the "Cambridge, MA"-centric narrative that Church weaves. The assumptions he makes about the casual links between the academy and the start-up are notable. Here, there is no questioning whether a professor should patent her research or whether he should start a company. These are presented as normative attitudes. Church’s account will be, I think, valuable to historians in terms of helping them see the assumptions and attitudes researchers had toward synthetic biology today. As time goes by, maybe we will see more evidence to reveal the tangled relations between syn bio and its progenitors. But for now, we have a compelling if only partial picture of the field as filtered through the competitive and/or collaborative relationships between syn bio’s alpha males.[Author's note: Now that the holidays are over and class is back in session, I'm going to hew to a more regular blog writing regime, hopefully with Leaping Robot posts on Fridays 2-3 times a month as my teaching/travel schedule permits.]