Monday, October 26, 2015

An unknowing inheritance: BBN's stop and go history in genetic engineering

When I joined BBN back in 2008, one of the new things I brought with me to the company was my research in synthetic biology.  I was a starry-eyed and naive recent Ph.D. graduate, and it was one of my little exploratory sidelines, which would not expand into a full-scale line of research for another two years, blooming as my AI work slowly withered away into neglect.  Nobody at BBN was even thinking about synthetic biology at the time, and nobody I was working with had any institutional memory of such research being done at BBN before, and so I assumed that must be so, and indeed for most intents and purposes it was so.

In fact, however, BBN has been a significant player in the work of genetic engineering at least twice before that I now know about.  One of those times I learned about several years ago, and is not the brightest of episodes for the community.  The other, however, I only learned about a short time ago, as I prepared to give a talk on the new SBOL 2.0 standard for encoding genetic designs, and it makes me both proud of my institution's history and amazed that it has somehow dropped out of its memory as an institution.

The nearer and less proud episode was BioSPICE, and it haunts my every step as a non-lab-centric researcher.  As best I understand the project (I was still a grad student chasing strong AI), in the early and heady days of the word "synthetic biology," a bunch of the leading researchers in the field made a try on the big goal of predictable simulation and engineering of organisms, at that point thinking they already had a sufficient critical mass of good tools and knowledge to take something like a straight-up electrical-engineering-style approach to the problem.  Thus, BioSPICE, a big DARPA-funded project to try to build the equivalent of the SPICE tool for simulation and engineering of electronics, which started with much fanfare in the early 2000s and much more quietly folded up shop a few years later.  I had known about some of the academic side (quite distantly at the time), but only later came to learn that BBN had been significantly involved in some way---I'm still not quite sure how, since the few stories I've gathered don't seem to correspond to what searching online turns up.  Years later on, when I would open my mouth to talk about the promise of model-driven design, it was often BioSPICE that dogged my heels, and fueled cries of, "We know that doesn't work, just remember BioSPICE!"  I have fought that history hard, all the way to the last few years when we've been finally able to start producing evidence that we really can predict biological circuits from their component parts.

The other episode of BBN's involvement with genetic engineering is much older, quite long before my time.  Back in 1982, when I was only four years old and the genetic engineering revolution not so much older, BBN began development of GenBank, probably the most important repository of biological information in the world.  What is it, and why is it so important?  GenBank stores genetic sequence information: it's where pretty much all the important scientific information about genes and genomes gets stored, one way of another.  BBN, with subcontracting help from another apparently unlikely collaborator, Los Alamos National Laboratory, put it together and ran it for its first few years of existence, as it became established and started gathering information.  Eventually, as it became less a research project in and of itself and its contents became more and more important, it moved to curation by the NIH, who still manage it to this day, as an exponentially growing resource made publicly available to all of humanity.  Perhaps it's not quite as big a deal to work on as the internet or email, but pretty close, in my books.

Somehow, though, we seem to have almost entirely forgotten this history, as a company,  It's not trumpeted on the list of accomplishments on our front page, nor bragged about in the "history of BBN" materials that people pass around. The only name I've been able to find so far who was associated with the project from BBN is Howard Bilofsky, who apparently spent 17 years at BBN before leaving in 1990 for a long, distinguished, and apparently ongoing career in the biotech industry.  Someday, I would love to look him up and learn a bit more about the hidden corners of our corporate history.

GenkBan and BioSpice, triumph and failure.  And now a third wave of biology at BBN, with me, trying to navigate these waters once again, as best my limited scientific sight can guide me.

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