Responsible Nanotechnology

Scientific Advances Require Blind Luck

So here I am at this conference on self-assembly, and I'm talking with people about Rothemund's DNA staple technique. The technique is elegant, simple, and powerful. Mix a long DNA strand with a bunch of short strands. The short strands bond to different regions of the long strand, and pucker it up into a shape.

Person after person has told me that they never would have expected this to work! I was really surprised at that, so I've started having conversations about it.

One of the most common reasons has to do with entropy. Perhaps it's not a coincidence that entropy is one of the most common objections to molecular manufacturing. There's a whole lot of very solid theory about entropy, which says that unstable molecules will fall apart. But what's often missed--by the people applying this theory!--is that it assumes a steady state, also known as infinite time! In other words, entropy says diamonds aren't literally forever... but in the real world, we can ignore that. Nanomachines built of diamond could laugh at entropy for far longer than we actually care about.

So, back to entropy vs. DNA self-assembly. I was talking with a physicist over lunch today, trying to figure out why he expected DNA shapes to fall apart on entropic grounds. It turned out that he was right - the shapes will eventually fall apart - but he hadn't thought about the time it would take.

Another entropy-related reason that's often cited is that DNA staple shapes require combining hundreds of molecules into a single structure, and the entropy of a single structure is a lot lower than the entropy of hundreds of fragments. While this is true, the fact remains that DNA does prefer to join in double strands. I haven't found anyone who can explain why increasing the number of strands would significantly reduce the willingness of each strand to join the structure - but I've found lots of people who seem to believe this would be the case.

I can understand how assumptions from one domain (say, the physics of small molecule chemistry at equilibrium) can make it difficult to invent a new concept in another domain (say, DNA binding). It's a bit harder for me to understand how that assumption wouldn't be questioned when confronted with a really good idea.

In fairness, it's true that many seemingly good ideas don't work for reasons that couldn't easily be foreseen. So rejecting a seemingly good idea isn't always a destructive thing to do - it can save a lot of effort that would be wasted trying to develop the idea only to discover that some minor practicality prevented it from actually working.

But I'm starting to think that the stated reason for rejecting the idea is frequently unrelated to the reason that the idea wouldn't actually work. In other words, science has developed a rule of thumb that works: Reject most ideas, accepting only the most compelling and fully demonstrated ones. And a procedure that works: To reject an idea, find and cite some overly-generalized and poorly understood theory. The fact that the procedure is groundless does not mean that science's rate of rejection of new ideas is wrong. The rate of rejecting new ideas may, in fact, be highly functional.

If the rejection of new ideas is basically random, then I'm saying that science advances by blind luck. In fact, that's plausible. Any exploration of a sufficiently unfamiliar and difficult problem domain must advance by blind luck. What makes science (and evolution) work is that they can, after the fact, detect and preserve lucky accidents.

A question we might ask is whether things would be better with a somewhat lower idea rejection rate, and if so, how to shift the rate. The answer is probably somewhere along the lines of increasing funding for researching crazy ideas. I don't know if there would be any point in trying to convince scientists that they're routinely rejecting ideas randomly.

Another question we might ask is what to do when scientific advances are needed to achieve a technological goal. The answer seems to be: Don't expect the scientific establishment, as a whole, to work toward that goal, no matter how workable or clearly articulated or well-calculated. The goal will simply be treated as a new idea, and rejected. Instead, find a way to pay individual scientists to work on it.

By the way, I just heard a talk in which a DNA cascade circuit was developed and tested to compute the square root of a four-bit number. It involved about 130 strands, implementing about 76 logic gates. It would be very easy to find a theoretical reason why this couldn't possibly work... but in fact, it did work.

Chris Phoenix

"Molecular Programming" Approaches Molecular Manufacturing

I'm sitting here at the Foundations of Nanotechnology conference, listening to a talk by Erik Winfree of CalTech. He's doing an excellent job of presenting molecular manufacturing ideas in a way that's acceptable to experimentalists. Not that he's explicitly supporting molecular manufacturing, but his work requires the ideas. While trying to build computational systems, he is working toward general-purpose manufacturing.

He started by invoking the goal of putting information into a chemical soup and getting a product. Basically, the molecular manufacturing vision. He acknowledged that we're not near that today... but the direction of his talk is clearly one of: Let's see how close we can get to that vision.

He called for getting beyond pure self-assembly: "You can do some things with passive self-assembly; you can do them much better if you're able to implement molecular motors."

He talked some about the ability to implement computer algorithms (Turing machines) with chemical reaction networks: possible in theory with arbitrarily low (but not zero) error rates. But it can take a large vat to implement a complex algorithm.

Now he's talking about DNA strands being used for computing. I was hoping he'd be talking more about fabrication of structures, but I guess in a way he is: computation with molecules does, physically, fabricate structures. And the fabrication of structures

Oh, good, now he'll talk about controlling growth using passive assembly. .... Oh, very cool. He's talking about how self-assembling tiles with carefully designed matching edges can implement any algorithmically-describable shape. And, of course, DNA can implement tiles with lots of different edge configurations.

He has a slide titled "Theory of Active Self-Assembly (of Molecular Robots)." It includes the statement, "Any algorithmically-describable shape can be assembled _efficiently_." He talked about shapes with a billion components and said they could be assembled exponentially. He acknowledges "This is something for the future" since we're still at the stage of molecular motors rather than molecular robots.

It will be very important to have physical systems that include large-ish blocks that self-assemble reliably. There's a whole lot of incorrect assumptions running around, even among cutting-edge molecular self-assembly people, professional chemists and physicists. Many of them are just not comfortable with this kind of system, and would not expect them to work, and will not be able to work on them until they drop some of their (mis-applied) theory. It will require experimental demonstration to shift the paradigms.

Winfree's work appears likely to produce tangible, even flashy results; to produce some results with today's tools, with gradual steps all the way to programmable molecular robots driving assembly mechanically.

If molecular manufacturing is not developed by a targeted program, it will require a series of paradigm shifts. Paradigm shifts are rare and difficult, but Winfree's work seems likely to fuel a few key shifts.

Chris Phoenix

Regulating Advanced Nanotech

An email correspondent asked an interesting question (thanks, Wendy!) about whether we've missed the moment to regulate molecular manufacturing.

I see two main sources of regulation, plus a distant third:

1) Commercial regulation, dealing with the economic implications of a manufacturing revolution.

2) Military regulation, dealing with the weapons and geopolitical aspects.

3) Maybe criminological regulation, since new products can often be used for new forms of crime.

I think commercial development of molecular manufacturing will likely be too fragmented for effective regulation. There may be some regulations that have substantial negative impact, comparable to the creation of software patents in the mid-1980's. But I suspect most commercial regulation will be trying to solve non-problems (defend obsolete monopolies) after the fact, and won't have too much impact.

A major question on military regulation is whether molecular manufacturing will be developed mainly on the commercial side, incrementally, as computers have been, or whether it will be developed first in a "Nanhattan" project. In the latter case, it might be seen as dangerous (especially if used in war in an especially flashy and gruesome way) and susceptible to blanket regulation. That could hamper commercial use for decades. But if molecular manufacturing develops incrementally, it may be no more regulated than computers or biotech.

Regulation of crimes and other social impacts will probably be about as effective as regulating illegal drugs.

Thoughts?

Chris Phoenix

Anticipating Bad Laws?

A few days ago, Tom Craver suggested that even if CRN couldn't promote good policy for the anticipated manufacturing breakthrough, we might be able to anticipate bad laws.

The idea was that if we knew what bad laws might get passed, "maybe you can convince those who will develop the nanofactories to take approaches that avoid triggering the worst traps until it's too late to mess MNT up too badly."

One approach, of course, might be to deny that molecular manufacturing is possible; not work on it openly; not develop any intermediate technologies; then, when it gets easy enough, suddenly produce a nanofactory in some out-of-the-way lab. By the time any laws got written, nanofactories might have proliferated too widely for laws to catch up.

Funny, but that seems to be what's happening today.

But there are at least two problems with this approach. First, the developers would have to give away the technology - quickly and widely - or risk it being quietly but firmly suppressed. It would be difficult to go from below-the-radar to desktop giveaway nanofactory before someone spilled the beans and brought in the feds.

Second, a free-for-all approach might not be the wisest...

Thoughts?

Chris Phoenix

CRN Inspired Cutting-Edge Nano-science

Back in 2005, I had several long discussions / debates (e.g. this discussion) with two scientists, Richard Jones and Philip Moriarty. They attempted to convince me that molecular manufacturing couldn't work. (Richard Jones is the author of Soft Machines, which argues that biochemical-based systems are far superior to diamond-like systems.) I attempted to convince them that it could. The argument was somewhat frustrating on both sides...

In an online interview, Philip Moriarty has recently acknowledged those discussions as being the inspiration for his current research: attempting to demonstrate or disprove calculations of atomic bond manipulation and structure formation - including 3D structures - on silicon and diamond surfaces.

In other words, he's trying to learn whether or not Drexler-style mechanical chemistry works the way it's been calculated to work. This does not make him a supporter of Drexler, but it does mean he has an open mind. Open-minded scientists are what makes science work, and Moriarty's work is doubly valuable for its rarity.

(Richard Jones, by the way, went on to lead a group that was convened in order to allocate several million dollars of scientific funding; the funds went toward projects that had the potential to substantially advance molecular manufacturing.)

I'm glad to see that CRN made this contribution to scientific progress in the field of molecular manufacturing.

(Hat tip to Brian Wang at NextBigFuture.com.)

Chris Phoenix