(credit: Comp. Cog. Neurosci Lab/ Olaf Sporns, Indiana Univ.)

A proposal alluded to by President Obama in his State of the Union address to construct a dynamic “functional connectome” Brain Activity Map (BAM) would leverage current progress in neuroscience, synthetic biology, and nanotechnology to develop a map of each firing of every neuron in the human brain—a hundred billion neurons sampled on millisecond time scales. Although not the intended goal of this effort, a project on this scale, if it is funded, should also indirectly advance efforts to develop artificial intelligence and atomically precise manufacturing. In his blog, Robert L. Blum provides an excellent overview and brief introduction. From “BAM: Brain Activity Map: Every Spike from Every Neuron“:

A recent research proposal called BAM for Brain Activity Map Project generated much excitement. (The BAM proposal, published in Neuron in June 2012 is online, and an earlier draft with far greater detail is also online.)

(Addendum: 18 Feb 2013: I started drafting this story in Nov, 2012. Today it was headline news when it was made public that THIS is the very proposal that President Obama alluded to in his recent State of the Union address. See John Markoff’s NY Times piece. NIH is drafting a 3 billion dollar, 10 year proposal to fund this project. Also see this 25 Feb 2013 NY Times follow-up by Markoff.) …

The essence of the BAM proposal is to create the technology over the coming decade to be able to record every spike from every neuron in the brain of a behaving organism. While this notion seems insanely ambitious, coming from a group of top investigators, the paper deserves scrutiny. At minimum it shows what might be achieved in the future by the combination of nanotechnology and neuroscience. …

The Neuron article cited by Blum argues that in addition to breakthroughs in basic science with large medical and economic benefits, the BAM project will advance technology in terms of important general capabilities.

Many technological breakthroughs are bound to arise from the BAM Project, as it is positioned at the convergence of biotechnology and nanotechnology. These new technologies could include optical techniques to image in 3D; sensitive, miniature, and intelligent nanosystems for fundamental investigations in the life sciences, medicine, engineering, and environmental applications; capabilities for storage and manipulation of massive data sets; and development of biologically inspired, computational devices.

I think the emphasis on nanosystems of nanodevices integrated to provide complex functions is very important, even if many or most of those devices will, in the beginning, not be atomically precise. The more detailed description of the BAM proposal cited by Blum above hints at how nanoparticle-based sensors could be developed to noninvasively provide micrometer-scale spatial resolution and millisecond-scale temporal resolution to groups of millions of neurons deep inside the brain of a living, active animal (or human). The mention combining semiconductor quantum dots and nanodiamonds with organic nanostructures to functionalize them, so that they may be directed to and embedded in neural membranes to monitor synapses. In addition, nanotubes or nanowires could be developed to deliver photons to specific locations, or collect or release specific chemicals. Further, they suggest developing graphene into membrane patches for detailed monitoring of neurons. Taken together, the requirements for this ambitious project entail the need to develop a variety of nanoparticles for specific applications, and then integrating multifunctional nanoprobes, nanoparticles, and nanodevices into large functional systems, and producing such nanosystems en masse.

In his NY Times report John Markoff notes the possible effect of this project on the development of artificial intelligence: “Moreover, the project holds the potential of paving the way for advances in artificial intelligence.” Indeed, the information to be provided by BAM about how circuits of thousands or millions of neurons work should advance Ray Kurzweil’s program of reverse engineering the human brain to develop artificial general intelligence, as described in his new book How to Create a Mind: The Secret of Human Thought Revealed.

The next best thing to large program to develop molecular manufacturing is a large program aimed at other worthy and useful goals that also makes heavy use of nanotechnology and may promote some of the same or similar enabling technologies that will lead toward productive nanosystems.
—James Lewis, PhD

Carl Bass, successor to the successor to the successor to me as CEO of Autodesk got up in front of an audience and spoke on “The Five New Rules of Innovation” among which was nanoscale and bio-inspired structures.

Unlike when I did it all those many years ago, nobody giggled.

And they say there isn’t progress!

Video (17 minutes–the nano bit is short, but it’s there):

John Walker’s thoughts on nanotechnoloogy were published about 22 years ago in a Foresight Briefing “What Next? Nanotechnology for Manufacturing“. The definitive copy of this essay, with the complete set of illustrations, is available on John Walker’s Web site.

Obsessive gamers’ hours at the computer have now topped scientists’ efforts to improve a model enzyme, in what researchers say is the first crowdsourced redesign of a protein.

The online game Foldit, developed by teams led by Zoran Popovic, director of the Center for Game Science, and biochemist David Baker, both at the University of Washington in Seattle, allows players to fiddle at folding proteins on their home computers in search of the best-scoring (lowest-energy) configurations.

The researchers have previously reported successes by Foldit players in folding proteins, but the latest work moves into the realm of protein design, a more open-ended problem. By posing a series of puzzles to Foldit players and then testing variations on the players’ best designs in the lab, researchers have created an enzyme with more than 18-fold higher activity than the original. The work was published January 22 in Nature Biotechnology [abstract].

“I worked for two years to make these enzymes better and I couldn’t do it,” says Justin Siegel, a post-doctoral researcher working in biophysics in Baker’s group. “Foldit players were able to make a large jump in structural space and I still don’t fully understand how they did it.” …

The latest effort involved an enzyme that catalyses one of a family of workhorse reactions in synthetic chemistry called Diels-Alder reactions. Members of this huge family of reactions are used throughout industry to synthesize everything from drugs to pesticides, but enzymes that catalyze Diels-Alder reactions have been elusive. In 2010, Baker and his team reported that they had designed a functional Diels–Alderase computationally from scratch [abstract], but, says Baker, “it wasn’t such a good enzyme”. The binding pocket for the pair of reactants was too open and activity was low. After their attempts to improve the enzyme plateaued, the team turned to Foldit.

In one puzzle, the researchers asked users to remodel one of four amino-acid loops on the enzyme to increase contact with the reactants. In another puzzle, players were asked for a design that would stabilize the new loop. The researchers got back nearly 70,000 designs for the first puzzle and 110,000 for the second, then synthesized a number of test enzymes based on the best designs, ultimately resulting in the final, 18-fold-more-active enzyme.…

The article was written by Jessica Marshall and reprinted in Scientific American with permission from Nature, where it was originally published as “Victory for crowdsourced biomolecule design: Players of the online game Foldit guide researchers to a better enzyme.” The article does an excellent job of describing how researchers and game players collaborated to achieve the final result. The gamers explored much more radical changes to the protein than can be done by conventional molecular biology techniques such as directed evolution, which typic[a]lly explores only single amino acid substitutions. The researchers then physically constructed and characterized the enzyme designed by the gamers.

The choice as design target of an enzyme to catalyze Diels-Alder reactions is particularly interesting from the standpoint of developing advanced nanotechnology, also referred to as molecular manufacturing. As noted in the 2010 Science paper, this reaction is a “cornerstone” in organic synthesis, and no naturally occurring enzymes are known to catalyze this reaction. As early as 1994 Markus Krummenacker proposed the use of Diels-Alder cycloaddition in a strategy to develop molecular building blocks for molecular manufacturing (“Steps towards molecular manufacturing“).

What roles crowd-sourcing, citizen science, and de novo protein design will play in the development of molecular manufacturing, or productive nanosystems, remains to be seen, but this latest result looks like an important step alog the way.
—James Lewis

Mimicking nature is a recurring theme in nanotechnology and molecular nanotechnology, inspired by the natural nanostructures found in our own bodies, offers many exciting potential outcomes.

“Molecular nanotechnology is the expected ability to build our products with molecular-level precision, as nature can do,” says Christine Peterson, president of the Foresight Nanotech Institute in California. “It will bring unprecedented quality, energy efficiency and environmental sustainability”.

The recent development of an electron-powered molecular “nanocar”, by a team led by chemist Ben Feringa at the University of Groningen in the Netherlands, hints at the potential. Further indications that molecular nanotechnology is achievable are being found in the quest for ever-smaller computing.

Many of these efforts attempt to use nature’s own method of storing and transferring information – DNA. “DNA computing is the goal of building devices out of DNA that are able to act like computers, initially doing simple calculations but eventually doing everything that a macroscale computer can do,” says Peterson. …

One future prospect for molecular-scale nanotechnology is to build nanofactories. “The nanofactory is a proposed compact molecular manufacturing system that could build a diverse selection of large-scale, atomically precise products,” explains Robert Freitas Jr, senior research fellow at the Institute for Molecular Manufacturing, also in California. “The products of a nanofactory would be atomically precise, with every atom in exactly the right place, offering the ultimate in quality control. It could make products out of the strongest materials known to man – especially diamond, sapphire, and related ultra-strong ceramics. In manufacturing, it’s hard to do better than that.”

The first two-dimensional structure to be built atom-by-atom was made from silicon in 2003. However, Freitas says nanofactories are still a long way off. “We expect this will require a 20-year research and development effort and on the order of $1bn (£622m) in funding to achieve.” …

If anyone knows someone with a billion dollars they will not need for twenty years, ask them to contact Christine or Robert.

… collects review articles from the six topics of the conference, while also including comments, discussions and debates obtained during the conference.

The issues discussed at this landmark conference were:

• Noncovalent Assemblies: Design and Synthesis
• Template Synthesis of Catenanes and Rotaxanes
• Molecular Machines Based on Catenanes and Rotaxanes
• Molecular Machines Based on Non-Interlocking Molecules
• Towards Molecular Logics and Artificial Photosynthesis
• From Single Molecules to Practical Devices

In addition, and this is probably the most novel feature of the book, comments, discussions and debate will constitute a substantial part of each chapter, in accordance with the tradition of Solvay Conferences.

On the Amazon web page above it is possible to “Search inside this book” to browse the Table of Contents, index, and several internal pages of the book.

The clear winner with 3,097 votes — 35 per cent of the total — is Catherine McTeigue’s prediction of nanorobots that will repair cancerous cells:

Nanorobots fight the medical battles of the future

“Say the word “cancer” and people are fear-ridden. Projects being undertaken to harness nanotechnology and develop nanorobots to enter into the human body and repair cancerous cells, without the need for life-changing, disfiguring and painful chemotherapy, will have the greatest impact in the next 30 years. Watching loved ones suffer will be a thing of the past as the robots aid speedy recoveries, mortality rates drop, and as the technology is used more frequently, so will the cost, that oft deciding factor. An enormous step forwards for all mankind, in the form of a microscopic creature.”

The winning suggestion is a bit vague as to just what kind of medical nanorobots are envisioned. Recent posts (here, here, and here) suggest that near-term, incremental nanotechnology could be successful in curing cancer by selectively killing cancer cells while sparing normal cells. However, the phrase “repair cancerous cells” suggests advanced medical nanotechnology, of the type Freitas has proposed, that could be capable of molecular level repair of cells rather than necessarily killing cancerous cells. On the other hand, using near-term nanotechnology to deliver into cancer cells siRNA or miRNA to alter cellular gene expression might also make it possible to “repair cancerous cells”. The next poll we would like to see is something to the effect of “How do you think medical nanorobots will be developed over the next 30 years?”