Wednesday, August 31, 2016

Biological Foundries

While in the UK, I had a gap in my schedule at IWBDA, and so I went to Edinburgh.  It was a lovely train ride up the coast from Newcastle, and for the first time in my life I had an opportunity to visit Scotland, birthplace of my McDonald and Houston ancestors.  Getting off the train at Edinburgh station, I was immediately struck by the remarkable degree to which the city is a center of culture, from the omnipresent Robert Burns quotes in the station to the theaters all about, not to mention the burgeoning festivals just beginning their month of explosion through the streets.  It was a fine warm, sunny day, and I immediately set off walking across the town toward my main business: visiting colleagues.

One of my stops that day was the Edinburgh Genome Foundry, one of only few such centers like it in the world. At present, I am aware of only eight: five in the US (Ginkgo Bioworks, Amyris, Zymergen, MIT/Broad, and Urbana-Champaign), two in the UK (Imperial and Edinburgh), and one at the National University of Singapore.  I may well be missing some, and others may be getting founded even as I speak (the UK and Singapore foundries are just getting off the ground), but the point is there's a small but growing number of such centers, both in industry and academia.

All of these foundries are aimed at much the same basic goal: to greatly increase the rate at which complex genetic materials can be engineered and tested. The focus differs somewhat from foundry to foundry: some are more focused on assembly, while others are more focused on information processing circuits, and yet others on chemical synthesis.  And of course, as each is its own unique cutting-edge experiment, the particulars of how each is set up are quite different. At their hearts, however, every foundry is the same, being essentially a robot-assisted machine shop for genes, formed of a number of stations of automated lab equipment, fluid-handling robots, and some combination of industrial manipulator arms and lab technicians to move materials from station to station.

Biological foundries are different than other laboratories incorporating automation in that they have much more flexibility, and with that flexibility comes a higher order of challenge in organizing the informational side of the foundries, and thus my interest.  In order to make a foundry work well, you need to have some sort of explicit representation of the genetic constructs that you are aiming to manipulate, the biological processes that you hope to create and affect by means of those constructs, and the various protocols and assays that you intend to perform in order to manufacture and evaluate them.  Much of that is well-represented by SBOL, and if they don’t choose SBOL they will likely end up having to recapitulate its development, so I am hoping we can ensure that all of the foundries adopt SBOL (it is being used within at least some already). Beyond that, I hold that it will also be important to for the foundries to adopt good unit calibration in their assays, and to consume that data in model-driven software design tools, in order to avoid some of the past tragedies of large biological characterization projects that produced largely non-reusable data.

Moreover, in a world with many biological foundries, I suspect that ultimately the ones that will have the largest impact will be those that open their processes and data and ensure that their works are recorded in good interchangeable standards.  Some are commercial concerns, of course, and that will limit their ability to share results out, but if those at least are able to take standardized information in, it will no doubt help them in the marketplace as well.  For biological foundries, like everything else, we no longer live in a world where isolated “moon shot” projects are a particularly competitive way to pursue either science or commerce, and I hope that their operators are well able to come to grips with this reality.
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