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In what fields would APM cause the most pronounced economic disruption and the collapse of global supply chains to more local chains?

The digital revolution had far-reaching effects on information industries. APM-based production promises to have similarly far-reaching effects, but transposed into the world of physical products. In thinking about implications for international trade and economic organization, three aspects should be kept in mind: a shift from scarce to common raw materials, a shift from long supply chains to more direct paths from raw materials to finished products, and a shift toward flexible, localized manufacturing based on production systems with capabilities that are comparable on-demand printing. This is enough to at least suggest the scope of the changes to expect from a mature form of APM-based production — which again is a clear prospect but emphatically not around the corner.
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-Posted by Stephanie C

(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

Mesocosms. Credit: Benjamin Coleman

The advent of new technologies is typically followed by new government regulation, and in the absence of data, fear-based reactionism can have far too much influence on policy. Quality research studies on real risks and impacts of nanoscale technologies can help lead to legitimate scientific consensus and appropriate regulation.

Engineered nanoparticles draw particular attention, because the same unique properties that give rise to special utility may also give rise to special health and environmental risks.

To calibrate our responses to nanoparticle toxicology studies, it is important to note whether an experiment reasonably represents likely exposure scenarios and whether nanoscale size is in fact a contributing factor to observed effects.

Recently highlighted at Phys.org, researchers at Duke University are investigating environmental impacts of widely used silver nanoparticles by way of experiments that seek to represent real-world exposure levels.

Previous studies have involved high concentrations of the nanoparticles in a laboratory setting, which the researchers point out, doesn’t represent “real-world” conditions.

For their studies, the researchers created mesocosms, which are small, man-made structures containing different plants and microorganisms meant to represent the environment. They applied sludge with low doses of silver nanoparticles in some of the mesocosms, then compared plants and microorganisms from treated and untreated mesocosms after 50 days.

“We’re trying to come up with the data that can be used to help regulators determine the risks to the environment from silver nanoparticle exposures,” [said Benjamin Colman, a post-doctoral fellow in Duke's biology department and a member of the Center for the Environmental Implications of Nanotechnology (CEINT)].

“Our results show that silver nanoparticles in the biosolids, added at concentrations that would be expected, caused ecosystem-level impacts,” Colman said.

The researchers plan to continue to study longer-term effects of silver nanoparticles and to examine another ubiquitous nanoparticle – titanium dioxide.

Studies that do not elucidate the roles of different particle properties can still be of great benefit by drawing attention to studies that do, and by adding to the pool of reliable data. Most important is for researchers and the public alike to recognize the difference and to support policy that is sensible and appropriate.
-Posted by Stephanie C

Would this sound like a potentially world-changing substance worthy of scientific attention and funding?

That substance is graphene, a single layer of graphite with hexagonally arranged carbon atoms (visualized as chicken wire).

Now imagine that the mechanical properties of this substance aren’t measured yet, as was the case for graphene before 2009. Imagine further that there is no way to grow or isolate the single-layer crystals in their free state, as was the case for graphene before 2004. Stepping back in time yet further, imagine that the theoretical work predicting massless charge carrier behavior hasn’t been carried out yet, as was the case for graphene before 1984.

Peeling back these milestones, we can see that if the scientific question being asked is “What can be realized from here?” then the graphene timeline played out characteristically, with major advancements coming primarily from opportunity-based research. In other words, over 50+ years, from the initial theoretical work on graphene in 1947 until stable monolayers were achieved in 2004, there was limited vision of what end-goals might be achievable and limited drive to get there.

What happens when a different question is asked, specifically “What can be realized according to physical law?” This is the key premise of the exploratory engineering approach, a methodology proposed by Eric Drexler for assessing the capabilities of future technologies. He points out, for example, that the principles of space flight had been worked out long before science and industry advanced enough to get to actual launch.

For initial space flight development, the answers to the two questions above were dramatically different: what could be done in practice was far behind what had been established as theoretically possible, and there was no defined path between them. By identifying what was achievable according to physical law, the longer-term goal of space flight entered the consciousness of physicists, engineers, and politicians, bringing great minds and great resources to the challenge.

With the benefit of similarly future-focused knowledge, perhaps graphene might have received far more attention far sooner. Consider this: the groundbreaking experimental work that sparked the field as we know it today was the discovery that single-layer graphene could be extracted from a piece of graphite by (essentially) pressing cellophane tape against it and peeling it away. In other words, a decades-long roadblock to achievements in graphene research was not a matter of inadequate supporting technology but one of limited scientific attention.

Here graphene serves as a useful illustration of how progress could potentially be hindered when opportunity-based research is relied upon exclusively. Scientific advancement could benefit significantly from deliberate, exploratory engineering. Perhaps there are numerous other ‘graphenes’ right now, going unnoticed or under-prioritized, because we are failing to ask: what can be realized according to physical law?
-Posted by Stephanie C

Darpa's Living Foundries program is looking to transform biology into an engineering practice. Photo: VA

Synthetic biology promises near-term breakthroughs in medicine, materials, and energy, and is also one promising development pathway leading to advanced nanotechnology and a general capability for programmable, atomically-precise manufacturing. Darpa (US Defense Advanced Research Projects Agency) has launched a new program that could greatly accelerate progress in synthetic biology by creating a library of standardized, modular biological units that could be used to build new devices and circuits. A hat tip to KurzweilAI.net for pointing to a recent article in Wired Danger Room “Darpa, Venter launch assembly line for genetic engineering“:

… The program, called “Living Foundries,” was first announced by the agency last year. Now, Darpa’s handed out seven research awards worth $15.5 million to six different companies and institutions. Among them are several Darpa favorites, including the University of Texas at Austin and the California Institute of Technology. Two contracts were also issued to the J. Craig Venter Institute. Dr. Venter is something of a biology superstar: He was among the first scientists to sequence a human genome, and his institute was, in 2010, the first to create a cell with entirely synthetic genome.

“Living Foundries” aspires to turn the slow, messy process of genetic engineering into a streamlined and standardized one. Of course, the field is already a burgeoning one: Scientists have tweaked cells in order to develop renewable petroleum and spider silk that’s tough as steel. And a host of companies are investigating the pharmaceutical and agricultural promise lurking — with some tinkering, of course — inside living cells.

But those breakthroughs, while exciting, have also been time-consuming and expensive. As Darpa notes, even the most cutting-edge synthetic biology projects “often take 7+ years and tens to hundreds of millions of dollars” to complete. Venter’s synthetic cell project, for example, cost an estimated $40 million.

Synthetic biology, as Darpa notes, has the potential to yield “new materials, novel capabilities, fuel and medicines” — everything from fuels to solar cells to vaccines could be produced by engineering different living cells. But the agency isn’t content to wait seven years for each new innovation. In fact, they want the capability for “on-demand production” of whatever bio-product suits the military’s immediate needs.

To do it, Darpa will need to revamp the process of bio-engineering — from the initial design of a new material, to its construction, to its subsequent efficacy evaluation. The starting point, and one that agency-funded researchers will have to create, is a library of “modular genetic parts”: Standardized biological units that can be assembled in different ways — like LEGO — to create different materials.

Once that library is created, the agency wants researchers to come up with a set of “parts, regulators, devices and circuits” that can reliably yield various genetic systems. After that, they’ll also need “test platforms” to quickly evaluate new bio-materials. Think of it as a biological assembly line: Products are designed, pieced together using standardized tools and techniques, and then tested for efficacy. …

The Darpa Living Foundries solicitation will remind long-term Nanodot readers of discussions of the need for an engineering perspective in the development of advanced nanotechnology centered on molecular manufacturing:

The Microsystems Technology Office (MTO) of the Defense Advanced Research Projects Agency (DARPA) is sponsoring an Industry Day for “Living Foundries,” a new DARPA program. The goal of the Living Foundries program is to apply an engineering framework to biology to harness its use as a technology and drive its advance as a manufacturing platform. In turning biological production into an engineering space where the only limit is the creativity of the designer, Living Foundries aims to enable on-demand production of new and high-value materials, devices and capabilities for the Department of Defense and establish a new manufacturing capability for the United States.

Because of the multidisciplinary nature of Living Foundries, DARPA is looking to engage the wider research community from fields both outside and inside the biological sciences to develop new ideas, approaches and tools to overcome current limitations and to create revolutionary capabilities.

Current, primitive examples of engineering biology rely on an ad hoc, laborious, trial-and-error process, wherein one successful project does not inform subsequent, new designs. This approach combined with the complexity of biological systems restricts current, one-off efforts to modifying only a small set of genes and constructing simple, isolated genetic circuits and metabolic pathways. Consequently, we are limited to producing only a small fraction of the vast number of possible chemicals, materials, and living systems that would be enabled by the ability to truly engineer biology. Through an engineering-driven approach to biology, Living Foundries aims to create a rapid, reliable manufacturing capability where multiple cellular functions can be fabricated, mixed and matched on demand and the whole system controlled by integrated circuitry, opening up the full space of biologically produced materials and systems. Key to success will be the democratization of the biological design and manufacturing process, breaking open the field to those outside the biological sciences.

In order to achieve the vision of Living Foundries, new tools, technologies and methodologies must be developed to transform biology into an engineering practice, decoupling design from fabrication and speeding the biological design, build, test cycle. These include: design tools that span from high-level description to fabrication in cells; modular genetic parts that allow a combination of systems to be designed and reproducibly assembled; methods for developing and fine-tuning new genetic parts and systems; well-understood test platforms, “cell-like” systems and chassis that readily integrate new genetic designs in a predictable fashion; next generation DNA synthesis and assembly techniques; and tools that allow for routine system characterization and debugging, among others. Further, these technological advances and innovations must be integrated to prove-out and push the boundaries of biological design towards the ultimate vision of point-of-use, on-demand, mass-customization biological manufacturing. …

If Darpa’s Living Foundries program achieves its ambitious goals, it should create a methodology, toolbox, and a large group of practitioners ready to pursue a synthetic biology pathway to building complex molecular machine systems, and eventually, atomically precise manufacturing systems.
—James Lewis, PhD

… Nanoscale forms of substances like silver, carbon, zinc and aluminum have many useful properties. Nano zinc oxide sunscreen goes on smoothly, for example, and nano carbon is lighter and stronger than its everyday or “bulk” form. But researchers say these products and others can also be ingested, inhaled or possibly absorbed through the skin. And they can seep into the environment during manufacturing or disposal.

Nanomaterials are engineered on the scale of a billionth of a meter, perhaps one ten-thousandth the width of a human hair, or less. Not enough is known about the effects, if any, that nanomaterials have on human health and the environment, according to a report issued by the academy’s expert panel. The report says that “critical gaps” in understanding have been identified but “have not been addressed with needed research.”

And because the nanotechnology market is expanding — it represented $225 billion in product sales in 2009 and is expected to grow rapidly in the next decade — “today’s exposure scenarios may not resemble those of the future,” the report says.

The panel called for a four-part research effort focusing on identifying sources of nanomaterial releases, processes that affect exposure and hazards, nanomaterial interactions at subcellular to ecosystem-wide levels and ways to accelerate research progress. …

A free PDF of the report A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials is available.
—James Lewis

…In the military’s latest round of small business solicitations, Darpa is making a long-shot request for an all-out replacement to antibiotics, the decades-old standard for killing or injuring bacteria to demolish a disease. In its place: the emerging field of nanomedicine would be used to fight bacterial threats. The agency’s “Rapidly Adaptable Nanotherapeutics” is after a versatile “platform capable of rapidly synthesizing therapeutic nanoparticles” to target unknown, evolving and even genetically engineered bioweapons.…

Darpa wants researchers to use nanoparticles — tiny, autonomous drug delivery systems that can carry molecules of medication anywhere in the body, and get them right into a targeted cell. Darpa would like to see nanoparticles loaded with “small interfering RNA (siRNA)” — a class of molecules that can target and shut down specific genes. If siRNA could be reprogrammed “on-the-fly” and applied to different pathogens, then the nanoparticles could be loaded up with the right siRNA molecules and sent directly to cells responsible for the infection.

Replacing a billion dollar industry that’s been a medical mainstay since 1940? Far fetched, sure, but researchers already know how to engineer siRNA and shove it into nanoparticles. They did it last year, during a trial that saw four primates survive infection with a deadly strain of Ebola Virus after injections of Ebola-targeted siRNA nanoparticles. Doing it quickly, and with unprecedented versatility, is another question. It can take decades for a new antibiotic to be studied and approved. Darpa seems to be after a system that can do the same job, in around a week. …

Using nanoparticles of various types to deliver therapeutic siRNA molecules is already a hot research area in nanomedicine (for example). The challenge here may lie in rapid DNA sequencing and good bioinformatics tools to find the best siRNA molecules to target novel bacterial threats.

A decade ago, University of Oregon chemist James E. Hutchison wrote an invited article in Chemical & Engineering News in which he envisioned “a generalized roadmap for the future design and development of green nanoscience materials.”

That roadmap has grown up and is now in front of chemistry leaders worldwide with the publication of “Green Nanotechnology Challenges and Opportunities.” The new “white paper” on the potential of incorporating benign chemistry practices was co-written by Hutchison. The American Chemical Society’s Green Chemistry Institute issued the document, which is freely available at www.acs.org/greenreport.

…

“The roots of green nano are really deep here in Oregon,” said Hutchison, who holds the Lokey-Harrington Chair in Chemistry at the UO. “This report mirrors the strategy that we have had for several years now. This is the way that things are going to be done. The report addresses the need for commercialization, for new policies — a new science for addressing our societal needs. It’s been 10 years in coming, but we are at the table now.”

The report outlines the promise of green nanotechnology, which promotes the design of useful particles thousands of times smaller than the width of a human hair in a way that reduces or eliminates waste or the production of hazardous substances. It also spells out what actions need to be undertaken by the various stakeholders, Hutchison said.

When successfully implemented, green nanotechnology could lead to a revitalized and sustainable U.S. chemical and materials manufacturing base, the white paper says. Nanoparticles could well find their ways into medicine, electronics, energy production and other industries.

“Green Nanotechnology Challenges and Opportunities” presents examples of both encouraging success in meeting the challenges of near-term nanoparticle development and reasons for concern that inept government regulation will retard progress.

A solid success is the development of sensitive assays for the biological effects of nanoparticle to be used to guide research and development of nanoparticles for applications. The combination of the embryonic zebrafish model with precisely engineered gold nanoparticles means that the effect of specific changes to charge, surface chemistry, and particle size can be investigated for subtle biological effects.

An example of the challenges yet to be overcome is the case of Dune Sciences. This company licensed a promising nanotechnnology innovation to permanently attach silver nanoparticles to surfaces so that commercial antimicrobial applications of silver nanoparticles could be developed without the worry of potentially toxic silver nanoparticles escaping into the environment. Unfortunately no path could be found through the EPA regulatory maze to register the product, despite the evident fact that the proposed product was safer than what was already on the market. This impasse prevented the company from securing funding and necessitated putting development of the product on hold.

The report also presents a brief analysis of the different barriers to developing nanotechnology in the US and in China that is worth a look.

Given Foresight’s interest in the long-term development of atomically precise productive nanosystems as a future manufacturing technology, with both its much greater potential benefits and its potentially more complex regulatory issues, the path forward being blazed by green nanotechnology is worth following.