Foresight Update 28
A publication of the Foresight Institute
Recent Progress (continued from previous page)
One of the natural applications of complex structures is catalysis. The 3D placement of active sites is important in the effective control of chemical reactions. In addition to its importance as an application area, this is important to nanotechnology as a source of new component parts, which may be applied in either parallel or sequential techniques for constructing new structures. The following three papers describe advances in the application and analysis of catalytic structures.
Synthesis of porphyrins by multi-enzyme, cell-free reactors
In the first paper, G. L. Verdine, writing in [Nature (supp) 384:11-13 7Nov96] describes the prospects for natural product chemistry in modern drug design. Amongst other developments, he describes the operation of a substantial enzyme cascade, writing: “The ease with which such in vitro biosynthetic reactions assemble complex organic molecules can be truly remarkable: in one case, a cocktail of 12 enzymes converted 5-aminolevulinic acid to hydrogenobyrininc acid, an advanced intermediate along the vitamin B12 biosynthetic pathway, giving a 20% overall yield. In a matter of hours, this bioreactor was able to catalyse a 17-step conversion with an average stepwise yield of 90%. … As recently as ten years ago, the notion of overproducing a dozen enzymes would have been greeted with derision, but recent advances in polymerase chain reaction-assisted overproduction systems and affinity tagging technology have greatly reduced the investment of time and labor necessary to obtain pure proteins in quantity.” This particular pathway is important to nanotechnologists because porphyrins such as B12 are rigid, fused, ring systems, potentially valuable as machine components. This application of an enzyme system in a cell-free reactor also allows a wider variety of potential substrates than in vivo techniques, including substrates, intermediates, and products that would be toxic to intact cells. The single vessel, multistep reactor is also analogous to the mill systems described in Nanosystems, albeit with diffusive transport.
X-ray diffraction pictures of molecular motions
In the second paper, V. Srajer et. al., writing in [Science 274:1726-1729 6Dec96], describe nanosecond x-ray diffraction analysis of structural changes during photolysis of the CO complex of myoglobin. They were able to measure shifts as small as an “iron displacement of 0.32 Å from the heme plane”. They are currently able to measure events as early as 4 nanoseconds after the laser dissociates the CO, but anticipate that the “time resolution can be extended to the 100-ps domain if shorter laser pulses are used.” At this point the length of the x-ray pulses, which are currently 150 ps long, will set the temporal resolution.
This technique will be very helpful in probing the sequence of conformations important in the operation of molecular machines, particularly when high flexibility may make unexpected structures accessible, as in biopolymer systems. One feature detected in the present study is a “transient docking site for the photodissociated CO”. In an analogous system designed for high speed operation, this might represent a detection of an unexpected speed limiting temporary trap, which is only visible in these transient structures. While this technique sees intermediate structures in a reaction, it is not generally fast enough to probe the potential energy surface in the neighborhood of unstable transition states themselves, where timescales are typically 0.1 ps. Those time scales are accessible to purely optical techniques, however this x-ray technique provides much more spatial information. One limitation of this paper’s technique is that it sees an average of the structures produced by a reaction, so too many accessible reaction pathways can average away useful information.
For further information, see:http://www.ucmc.uchicago.edu/news/1996/molecular.movie.html
Catalytic DNA and combinatorial chemistry
In the third paper, R. Rawls, writing in [C&EN 75:33-35 3Feb97], describes work by a number of labs on catalytic DNA. Rawls writes that “DNA is an ideal molecule to investigate using combinational chemistry” and all of the labs involved have used combinational techniques to select their catalysts. The reactions catalyzed have included RNA cleavage, DNA cleavage, DNA ligation, and metal insertion into porphyrins. The DNA catalysts have been much smaller than comparable protein catalysts. For example, D. Sen’s DNA for porphyrin metallation “has a molecular weight of roughly 8,000” while a mammalian protein that catalyzes the same reaction has a weight of around 42,000. Since these catalysts are DNA, they may be relatively simple to incorporate into 3D DNA frameworks, such as those that N. Seeman has developed, allowing 3D placement of several catalytic sites. In addition, the small size of the DNA catalysts may allow the same function to be contained in a smaller volume than would be required for protein catalysts.
One technique that is expected to become important in nanotechnology is mechanochemistry, the process of directing chemical reactions by mechanical forces on the reactants. The following paper describes experimental work in this area.
An AFM experiment by S. P. Jarvis et. al [Nature 384: 247-249 21Nov96] succeeded in tracing the force curve of an Si/Si tip/substrate pair smoothly through the negative stiffness regime. They augmented the force feedback of their lever with a magnetic feedback loop to increase the effective d.c. stiffness to 37 N/m. They measured the force curve by slightly perturbing the force at a frequency above the response of the feedback loop but below the free resonance frequency of their AFM lever, measuring the displacement (and hence the effective stiffness of the tip/sample interaction). They integrated the stiffness to yield the force curve, and integrated the force curve to yield the effective potential, finding “the energy point of inflection is at 2.5 eV, and that the maximum (tensile) force is just under 0.3 nN, not impossibly far from the expected ~1.5 nN for a single Si-Si bond, and rather larger than expected for a purely Van der Waals bond.” They found almost no hysteresis in their force curve with feedback turned on, “observing a conservative potential interaction.” This is experimental evidence for thermodynamically reversible mechanochemistry, in a silicon analog of the sp3 carbon bond cleavage case analyzed in section 8.5.3 of Drexler’s Nanosystems.
Jeffrey Soreff is a researcher at IBM with an interest in nanotechnology
General circulation media have given much attention to the prospects of nanotechnology in recent months, mostly favorably and accurately. The principal exception is a publication that usually does better, the New York Times.
Newsweek Magazine’s January 27, 1997, cover story took a peek into the next millennium, and found nanotechnology a likely part of the future. In the section devoted to science, “Uncovering Secrets, Big and Small,” science writer Sharon Begley started by describing DNA-related advances such as “gene pharming” that seem “certain to occur.” She then turned immediately to the prospects of nanotechnology:
“Wilder forecasts have stiffer odds. Will the 21st century see nano-assemblers? These microrobots would break down the chemical bonds of cheap ingredients – grass and water, say– and reassemble the carbon, nitrogen, hydrogen and other molecules into, for instance, a sirloin steak. You scoff? It is not much more incredible than a cow’s ability to do the same. And scanning tunneling microscopes can already manipulate single atoms, which is what the assemblers would do.”
Concluding the three-page article, Begley returns to the promise of nanotechnology:
“Dudley Herschbach of Harvard University foresees making molecules that self-assemble and self-replicate, sometime in the next 35 years. Biochemists are close to doing it. And they have a good idea of what to do with those creations: make those grass-into-sirloin nano-assemblers. In 1997 that seems like so much science fiction, while genetic discoveries, for instance, seem like sure bets. But sometimes, in science, the dark horse comes in before the favorite.”
The Philadelphia Inquirer published one of the best discussions of nanotechnology we’ve seen in the general press. Staff Writer Reid Kanaley captured the theoretical basis of nanotechnology, its promise, and its possible economic implications. Kanaley drew upon interviews with leaders in the field, including Rice University Nobel Laureate Richard Smalley, computational nanotechnologist Ralph Merkle of Xerox PARC, chemist Nadrian C. Seeman of New York University (winner of Foresight’s 1995 Feynman Prize), Al Globus of NASA (co-chair with Merkle of the upcoming Foresight Nanotechnology Conference), Foresight Institute’s Chris Peterson, and others. Kanaley accurately communicated the concept of “utility fog“, described how it could create skyscrapers, and carefully discriminated between molecular nanotechnology and unrelated “top down” efforts at miniaturization.
“Nanotechnologists drawing on advances in engineering, biotechnology and computer science want to use individual atoms as if they were Tinkertoys to create new materials and products that in some cases– like those fictional self-constructed buildings– could mimic living organisms, reproduce, and even assemble still other objects when turned loose by the trillions,” Kanaley wrote.
Smalley is quoted as describing molecular nanotechnology as “a very broad field and in many ways, the ultimate playground.” Futurist Arthur Shostak of Drexel University is quoted discussing the major social and economic upheaval if nanotechnology succeeds in extending life span or in replicating raw materials, or food. “Nano threatens the entire production infrastructure that you and I take for granted,” he said.
Merkle is quoted on the notion of self-replication as the basis for nanotechnology. “Potatoes don’t cost very much, even though they are miracles of biology with tens of thousands of genes and proteins. The reason they are inexpensive is that a potato can make more potatoes,” he said.
Technical Review, a publication of the Massachusetts Institute of Technology, featured a major article by Ralph Merkle, “It’s a Small, Small, Small, Small World,” in which he laid out the concepts of nanotechnology and the current state of the field. “Natural diamond is expensive, we can’t make it in the shapes we want, and it shatters. Nanotechnology will let us inexpensively make shatterproof diamond (with a structure that might resemble diamond fibers) in exactly the shapes we want. This would let us make a Boeing 747 that would weight one-fiftieth of today’s version without any sacrifice in strength,” Merkle wrote. Merkle has placed an expanded version of his article on his Web site.
Scientific American‘s February 1997 issue included a half-page article under the heading “Nanotechnology: Scoring with Buckyballs.” Writer Erica Garcia discussed Dr. Smalley’s use of fullerene tubes into scanning-force microscope (SFM) probes, noting their durability against “crashes” because of inherent flexibility. The same article pictured and discussed a molecular-sized abacus created at IBM Zurich Research Laboratory by Dr. James Gimzewski (a scheduled speaker at this fall’s Foresight Conference on Molecular Nanotechnology). His prototype calculator lines up buckyballs on a grooved copper plate, allowing abacus-like manipulation of the molecular “beads” with a scanning tunneling microscope (STM). He’s quoted as noting that this is the scale equivalent of “operating a standard abacus with the Eiffel Tower,” but the story notes that “by showing what is possible, buckyballs are starting to score big in the small field of nanotechnology.”
Muddled identity permeated a New York Times article in January that not only mistakenly identified micro-electromechanical systems (MEMS) as the equivalent of nanotechnology, but also misidentified the creator of the concept as “Eric Drexel”, and wrongly asserted that “the field of nanotechnology, practically speaking, has not done much since the late physicist Richard Feynman laid out its plans.” Eh? Didn’t the Times cover Smalley’s Nobel Prize for work in nanotechnology? The article is more a discussion about science fiction (Gibson’s Idoru and Stephenson’s Diamond Age) than science. It’s definitely not worth searching out.
Man clones sheep. Man clones monkeys. What’s next, an army of super-warriors? The near-hysterical reactions within media and government circles to these developments offers one potential scenario for considering the reverberations that could occur when nanotechnology is realized. Self-proclaimed experts weighed in with lofty opinions, many of which misrepresented the science, the ethical issues, or both. The Economist summarized the media reaction well:
“The news of Dolly hit the headlines with a sickening thud– the sound of a sheep that had been launched at full speed at the world’s pundits. And the pundits did not disappoint. Their responses were dismissive, scared, funny, outrageous, wise and stupid by turns. The important thing, it seemed, was to think of something to say, and say it first. Journalists, hungry for copy, swallowed their quotes and spread them on the page, in between invoking Aldous Huxley’s ‘Brave New World’ and Ira Levin’s ‘The Boys from Brazil’– apparently the only literary references to cloning anyone could remember….President Clinton, meanwhile, had only to say that there were ‘serious ethical questions’ to generate gravitas. One of the advantages of being president is that no one has the termerity to ask you too closely what the questions are.”
Newsweek’s Sharon Begley (see above) also offered a thoughtful discussion of the ethical and science issues, but concluded with a blunt assessment:
“If Dolly’s creation offers any lessons, it is these. First, that which is not absolutely prohibited by the laws of nature is possible. Second, science, for better or worse, almost always wins; ethical qualms may throw some roadblocks in its path, or affect how widespread a technique becomes, but rarely is moral queasiness a match for the onslaught of science.”
One positive aspect of the debate over human cloning is that it creates yet another difficult mixture of science and ethics that will give society practice in dealing with such fusions prior to having to come to grips with the potentially controversial applications of nanotechnology.