On the gripping hand

I just got through going to DNA17, which is one of the two big conferences put on every year under the auspices of the ISNSCE … the International Society for Nanoscale Sicence, Computation, and Engineering (isnsce.org). Ha, I remembered … which really shouldn’t be such a travail, since I’m currently President of this Society. What, you may ask? Why is a non-nano-ite such as myself on point for these folks? Long story, but suffice it to say that they are all very fun, as you’ll see in a moment.

And I should take this opportunity to mention / plug the third conference that will appear under ISNSCE auspices, BIOMOD (biomod.net), the International Bio-molecular Design Competition. This is the dreamchild of Shawn Douglas, currently of the Wyss Institute, but I do hope the ISNSCE maintains its association with this burst of youthful energy in some way into the future. BIOMOD will be to DNA nanotechnology what iGEM was to synthetic biology: a definition, a source of future leaders, and kickass fun as long as it remains relatively freeform (unlike the more recent iGEMs).

What I like about the DNA nanotechnology field is that it’s a technology in search of an application. This was nowhere more apparent than at the first panel discussion, which featured Ned Seeman, Erik Winfree, Eric Klavins, and Luca Cardelli. Each panelist had their own take on “Visions for DNA Computing and Molecular Programming.” Ned stressed control and precision, as he always does. We need to be able to place atoms with greater surety. Erik emphasized complexity, as he always does. We need to be able to build circuits that are ever more complex, and that will eventually scale as does electronic circuitry. Eric Klavins suggested that we needed to crossover to biology, using the remarkable toolsets that we have developed to better program metabolism and organisms.

I think each of these is a laudable vision, and is likely a vision shared by many in the community. I also think that each of these visions is … incomplete. Even though by this point it may seem like I disagree with thought leaders just for the sake of disagreeing, that’s really not true. Like lots of scientists, I just tend to have my own vision, and a lack of humility to go with it.

In the science fiction classic The Mote in God’s Eye, we are introduced to the Moties, a species that is trapped near a star without interstellar travel, but that has evolved extraordinary abilities. Anatomically, the Moties have two normal hands … and a third one, which gives them the ability to make and manipulate tools with great dexterity. This leads to the idiom of “on the gripping hand,” following “on the one hand or the other,” and suggesting another way, a better alternative.

This phrase was one I’ve kept with me throughout my life (and is suggestive of the power of good science fiction to hopefully foment good science). I find that many fields devolve into orthodoxy rather quickly. Indeed, new fields tend to have greater orthodoxy than most, because the pioneers have had to plow some hard rows in order to have their science be more broadly accepted. So, from my own vantage, I am President of the ISNSCE because I am obviously a heretic. I often wage pitched battles against orthodoxies of all sorts.

So, with that in mind, I arrogantly review the panelists’ points. Ned is right, greater control is necessary. But greater control is far from the only way to pursue DNA nanotechnology. DNA origami (ala Paul Rothemund) is a heresy on the controlled DNA structures Ned has spent a wondrous lifetime building. We need to keep in mind that self-assembly can and probably should at some level be a messy, error-prone, robust process. Erik is right, we need greater complexity. But DNA is decidedly not electronics, and never will be. Earlier in the field, there was the notion that DNA could compete with computers, via massive parallelization. This quickly proved false, and led to a retrenchment that Erik’s circuits are just now beginning to move beyond. Still, I think the same danger remains, of looking at computers and trying to … be them … but with grossly inadequate maceomolecular tools. Eric Kalvins is also right, that DNA nanotechnology has much to teach biology. This is especially true given the recent glorious demonstration from Pam Silver’s lab that organized, functional RNA structures could be generated inside of cells. There may indeed be input/output devices based on DNA nanostructures and circuits, and these input/output devices may operate on nanostructured platforms built inside of cells. But in the end, the cellular operating system is as foreign to many of the concepts of DNA nanotechnology as the latter is to electronics. Cells are evolutionary machines that have crafted operating systems that work without design. To now impose design is akin to what the Tea Party seeks to do with the US Constitution in ignoring hundreds of years of court interpretations. It can be done, but it would be pretty primitive compared to where we are now.

Which brings us to the gripping hand. I believe the same two core principles that virtually everyone at DNA17 accepted as a given: (a) that in order to manipulate matter at the nanoscale, you have to have an information-rich, programmable structure such as DNA, and (b) that there is something very special about matter computation, molecules executing their own instruction sets, and again this requires an information-rich, programmable structure such as DNA. But I also believe that these two core principles strongly argue against DNA nanotechnology being either electronics or biology. I believe it will be the gripping hand, a new operating system better than either of its predecessors. And it will run on a platform yet to be conceived, a matter computer made for the execution of DNA circuitry.

And since I am so obviously a non-nano-ite, I can without fear of conflict of interest add the following: program managers take note. These folks may not know exactly what they want to build, but what they will build will change the world in a very profound way.


- originally posted on Sunday, September 25th, 2011