Christine Peterson

Foresight Co-Founder and Past President Christine Peterson is interviewed on the Singularity Weblog in a 47-minute tour that covers nanotechnology, the founding of the Foresight Institute, her work on personal life extension through Health Activator, open source, and the Technological Singularity. “Christine Peterson on Singularity 1 on 1: Join Us to Push the Future in a Positive Direction“:

During my Singularity 1 on 1 interview with Christine Peterson we discuss a variety of topics such as: how she got interested in nanotechnology and the definition thereof; how, together with Eric Drexler, she started the Foresight Institute for Nanotechnology; her interest in life extension; Dr. Drexler’s seminal book Engines of Creation; cryonics and chemical brain preservation; 23andMe and other high- and low-tech tips for improved longevity; whether we should fear nanotechnology or not; the 3 most exciting promises of nanotech; women in technology; coining the term “open source” and using Apple computers; the technological singularity and her take on it…

Hear Christine discuss some challenges while presenting an essentially optimistic message—a wonderful future is coming from science and technology over the next few decades—a future that encourages everyone to get involved.
—James Lewis, PhD

Scientists are one step closer to making more complex microscopic biological machines, following improvements in the way that they can “re-wire” DNA in yeast, according to research published today in the journal PLoS ONE [open access article].

The researchers, from Imperial College London, have demonstrated a way of creating a new type of biological “wire”, using proteins that interact with DNA and behave like wires in electronic circuitry. The scientists say the advantage of their new biological wire is that it can be re-engineered over and over again to create potentially billions of connections between DNA components. Previously, scientists have had a limited number of “wires” available with which to link DNA components in biological machines, restricting the complexity that could be achieved.

The team has also developed more of the fundamental DNA components, called “promoters”, which are needed for re-programming yeast to perform different tasks. Scientists currently have a very limited catalogue of components from which to engineer biological machines. By enlarging the components pool and making it freely available to the scientific community via rapid Open Access publication, the team in today’s study aims to spur on development in the field of synthetic biology.

Future applications of this work could include tiny yeast-based machines that can be dropped into water supplies to detect contaminants, and yeast that records environmental conditions during the manufacture of biofuels to determine if improvements can be made to the production process.

Dr Tom Ellis, senior author of the paper from the Centre for Synthetic Biology and Innovation and the Department of Bioengineering at Imperial College London, says: “From viticulture to making bread, humans have been working with yeast for thousands of years to enhance society. Excitingly, our work is taking us closer to developing more complex biological machines with yeast. These tiny biological machines could help to improve things such as pollution monitoring and cleaner fuels, which could make a difference in all our lives.”

Dr Benjamin Blount, first author of the paper from the Centre for Synthetic Biology and Innovation and the Department of Bioengineering at Imperial College London, says: “Our new approach to re-wiring yeast opens the door to an exciting array of more complex biological devices, including cells engineered to carry out tasks similar to computers.”

In the study, the Imperial researchers modified a protein-based technology called TAL Effectors, which produce TALOR proteins, with similar qualities to wires in electronic devices. These TALORS can be easily re-engineered, which means that they can connect with many DNA-based components without causing a short circuit in the device.

The team says their research now provides biological engineers working in yeast with a valuable new toolbox.

Professor Richard Kitney, Co-Director of the Centre for Synthetic Biology and Innovation at the College, adds: “The work by Dr Ellis and the team at the Centre really takes us closer to developing much more complex biological machines with yeast, which may help to usher in a new age where biological machines could help to improve our health, the way we work, play and live.”

Professor Paul Freemont, Co-Director of the Centre for Synthetic Biology and Innovation at the College, concludes: “One of the core aims of the Centre is to provide tools and resources to the wider scientific community by sharing our research. Dr Ellis’s team has now begun to assemble characterised biological parts for yeast that will be available to researchers both in academia and industry.”

Promoters are DNA sequences that signal transcription of a gene to make a messenger RNA molecule that is then translated to make the protein product encoded by the gene. By systematically mutagenizing the core sequence of one promoter, the researchers created a library of 36 promoters that could be independently regulated. They also created a library of proteins to specifically turn off individual variant promoters. They thus designed a complex network of gene regulation that can be used for arbitrary engineering purposes rather than those networks that have evolved to fit the yeast’s own metabolic needs. One wonderful aspect of this work is that, not only are the results published in an open access journal rather than sequestered behind a pay wall, but the biological “parts” created are available to other biological engineers to elaborate the toolbox that is available to synthetic biology and, perhaps eventually, for a folded polymer path toward productive nanosystems. IMHO, this collaborative “Open Source-like” approach being pursued in synthetic biology provides an admirable paradigm for the development of advanced nanotechnology.
—James Lewis, PhD

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

Hope to see you there!  —Christine Peterson, President, Foresight Institute

“Christine Peterson, president of the Foresight Institute based in Palo Alto, California, warns that without safeguards, the data we gather about each other might one day be used to undermine rather than to protect our freedom. ‘We are moving to a new level of data collection that our society is not accustomed to,’ she says.” …

“‘We need to look urgently at who is getting the data, what they are doing with it, what it does to our freedoms and whether the information can be abused,’ she says. ‘And we need to think about these things now.’”

Establishing standards now for current and near future widespread sensing based upon smart phones owned by individual members of the public will set precedence for considering the future in which MEMS and nanotechnology will make truly ubiquitous and thorough sensing inexpensive.

…Remarkably, the ebb and flow of activity in these networks can perform computations of arbitrary complexity in principle — in fact, we describe a compiler that translates digital logic circuits into functionally equivalent seesaw gate networks, and we argue that the simplicity of the motif should make networks containing thousands of gates possible. If this theoretical proposal pans out experimentally, could it become a core technology for embedding circuitry in synthetic biochemical systems?

A recent experimental implementation is described in a Caltech news release written by Marcus Woo “Caltech Researchers Build Largest Biochemical Circuit Out of Small Synthetic DNA Molecules“:

In many ways, life is like a computer. An organism’s genome is the software that tells the cellular and molecular machinery—the hardware—what to do. But instead of electronic circuitry, life relies on biochemical circuitry—complex networks of reactions and pathways that enable organisms to function. Now, researchers at the California Institute of Technology (Caltech) have built the most complex biochemical circuit ever created from scratch, made with DNA-based devices in a test tube that are analogous to the electronic transistors on a computer chip.

Engineering these circuits allows researchers to explore the principles of information processing in biological systems, and to design biochemical pathways with decision-making capabilities. Such circuits would give biochemists unprecedented control in designing chemical reactions for applications in biological and chemical engineering and industries. For example, in the future a synthetic biochemical circuit could be introduced into a clinical blood sample, detect the levels of a variety of molecules in the sample, and integrate that information into a diagnosis of the pathology.

“We’re trying to borrow the ideas that have had huge success in the electronic world, such as abstract representations of computing operations, programming languages, and compilers, and apply them to the biomolecular world,” says Lulu Qian, a senior postdoctoral scholar in bioengineering at Caltech and lead author on a paper published in the June 3 issue of the journal Science. ["Scaling Up Digital Circuit Computation with DNA Strand Displacement Cascades" abstract]

Along with Erik Winfree, Caltech professor of computer science, computation and neural systems, and bioengineering, Qian used a new kind of DNA-based component to build the largest artificial biochemical circuit ever made. … The researchers’ new approach … involves components that are simple, standardized, reliable, and scalable, meaning that even bigger and more complex circuits can be made and still work reliably. …

To build their circuits, the researchers used pieces of DNA to make so-called logic gates—devices that produce on-off output signals in response to on-off input signals. … Instead of depending on electrons flowing in and out of transistors, DNA-based logic gates receive and produce molecules as signals. The molecular signals travel from one specific gate to another, connecting the circuit as if they were wires. …

Their new logic gates are made from pieces of either short, single-stranded DNA or partially double-stranded DNA in which single strands stick out like tails from the DNA’s double helix. The single-stranded DNA molecules act as input and output signals that interact with the partially double-stranded ones. …

Qian and Winfree made several circuits with their approach, but the largest—containing 74 different DNA molecules—can compute the square root of any number up to 15 (technically speaking, any four-bit binary number) and round down the answer to the nearest integer. The researchers then monitor the concentrations of output molecules during the calculations to determine the answer. The calculation takes about 10 hours, so it won’t replace your laptop anytime soon. But the purpose of these circuits isn’t to compete with electronics; it’s to give scientists logical control over biochemical processes. …

Because the logic gates have identical structures, they can be standardized and wired together to make any desired circuit. The authors have provided an online compiler (with a source code that can be downloaded) to give the DNA sequences for any digital circuit.

“Like Moore’s Law for silicon electronics, which says that computers are growing exponentially smaller and more powerful every year, molecular systems developed with DNA nanotechnology have been doubling in size roughly every three years,” Winfree says. Qian adds, “The dream is that synthetic biochemical circuits will one day achieve complexities comparable to life itself.”

The authors have explained their process with a delightful YouTube video, The Seesaw Magic Book. Among the several informative commentaries on this research is “DNA logic gates calculate square root using 130 different molecules” by John Timmer:

… Still, it does have its appeal. Various biomolecules, including DNA, RNA, enzymes, and small molecules, could all potentially be used as inputs. And it should be possible to link the outputs into relevant biological functions, including gene expression. Finally, the authors have a rather clever idea to speed things up. Instead of having all the gates floating loose in a test tube, they suggest that it might be possible to use large DNA scaffolds to assemble gates in close proximity to each other, ensuring that reactions take place quickly and require far less DNA to be used.

Willow Garage, the Menlo Park, California-based consortium of robotics experts, founded by Scott Hassan in 2006 to create or develop hardware and open source software for the advancement of robotics, has announced the release of TurtleBot; a small home use robot for either amusement/entertainment purposes, or for those inclined, to build open source applications to add to the functionality of the new robot.

The idea behind TurtleBot, is to give novice robotics enthusiasts a base upon which to build. Traditionally, those that like to tinker with robots have had to start from scratch every time they wanted to build something; the TurtleBot does away with that concept by supplying users with a base upon which they can build, as the TurtleBot comes fully functional. Out of the box it can map your house with its 3-D vision, bring you food, take 360 degree panorama pictures and follow you around etc. But it also comes with the Robot Operating System (ROS) and associated toolkit, so that if users wish to add or change functionality, they are free to do so, and because its open source, anything they create can be shared with friends or those involved in online robotics communities.

Another objective of the TurtleBot team was to show that such a device could be put on the market for a reasonable price; in this case $500, for a very basic unit, and $1200 for the fully loaded version. Far below what robot enthusiasts have come to expect to pay. …

For more information, see this IEEE Spectrum blog and this Willow Garage overview, where you can alsso preorder for shipment “in early summer”. Willow Garage and open source robotics has been a topic of a number of Nanodot posts since 2009.

…In a series of recent papers, researchers at MIT’s Computer Science and Artificial Intelligence Laboratory have demonstrated a promising new technique for modeling such protein folding. While not as accurate as some existing techniques, it is much more computationally efficient. Sophisticated, atom-by-atom simulations that run on hundreds of thousands of computers might take months to model a few milliseconds of protein folding. The researchers’ new technique can model the same process in minutes on a single laptop.

Speed is of the essence as the amount of unprocessed genomic data proliferates. “There’s the Broad 1,000 Genomes project, there’s X many species that have been sequenced now, and the sequence data is just vastly outpacing the speed with which you could apply some of these other techniques,” says Charles O’Donnell, a PhD student in the Department of Electrical Engineering and Computer Science who helped develop the new approach. “If you want to make sense of all this high-throughput data that’s coming from this great biotech innovation, then you need something quick.”

Other “quick” methods of simulating protein folding exist, but the MIT researchers’ appears to be more accurate. There is still much we don’t know about the actual structure of proteins, O’Donnell cautions, so that makes assessing the quality of computational methods difficult. But at the 19th Annual International Conference on Intelligent Systems for Molecular Biology (ISMB) in July, the MIT researchers will present a paper demonstrating that for a class of proteins known as amyloids, their technique’s predictions match the currently available data with 81 percent accuracy, whereas high-efficiency techniques previously managed 42 percent at best.

Computational modeling of protein folding has been an active research area for decades, but “it hasn’t been entirely clear whether it was going to be useful or not,” says Susan Lindquist, an MIT professor of biology, recent recipient of the National Medal of Science, and, along with CSAIL’s Bonnie Berger and Srini Devadas, one of O’Donnell’s faculty advisors. “I think that this paper helps realize that goal.” …

“Protein folding continues to be wide-open problem with desperate need of more rigorous mathematical, statistical and computer-science approaches,” says Sorin Istrail, a professor of computer science at Brown University who specializes in computational biology. What distinguishes the MIT researchers’ work, he says, is its “rigorously mathematical results.” “The world needs to do what Bonnie and Charlie are doing,” Istrail says, “taking one aspect of the problem and building rigorous methods for that particular component.”

For those who would like to learn more about these new computational approaches to protein folding to see if they might be useful for protein design work for advanced nanotechnology, many of the papers can be downloaded from O’Donnell’s web site, and a number of public domain programs for protein structure prediction are available from Berger’s web site.

Scientific researchers need to keep notes. What better way to journal a journey into a specific scientific project than on a blog? While a reader may not find specific details about a science experiment, researchers can offer insights, news, trends and projects. These top 50 blogs by scientific researchers include individuals who focus on open source and open access, academia, projects funded by organizations and news produced by writers who research science.

The blogs are organized into “Academic Blogs,” “Research Blogs,” “Open Access | Open Source,” “Organizations, Businesses and Tools,” and “Other Blogs”. All of the half dozen blogs I looked at were worth my time. The section on open access, open source and open science was especially informative. To give just one example, the Useful Chemistry blog opens with a report on the “Nanoinformatics 2010 Conference Report:”

On November 3, 2010 I presented on “The implications of Open Notebook Science and other new forms of scientific communication for Nanoinformatics” at the Nanoinformatics 2010 conference.

The presentation first covers the use of the laboratory knowledge management system SMIRP for nanotechnology applications during the period of 1999-2001 at Drexel University. The exporting of single experiments from SMIRP and publication to the Chemistry Preprint Archive is then described followed by the evolution to Open Notebook Science in 2005. Abstraction of semantic structure from ONS projects in the areas of drug discovery and solubility is then detailed as an efficient mechanism to provide web services and machine readable data feeds.

This was a terrific opportunity to tie together my current ONS projects with my work in nanotechnology about 10 years ago, when the focus was to capture laboratory information in a structured format so that autonomous agent could begin to replace human workflows. I found it really interesting that the most active workflows back then were related to processing reference information. It took a team of students to find, photocopy and scan many of our key papers, with all the problems that come with training and managing new students. Today, obtaining relevant papers and extracting metadata is not so much of a challenge with tools like Mendeley. I ended the talk with a mention of our use of Mendeley tags to share dynamic links of article collections. …

Whether or not Open Science will get us advanced nanotechnology and artificial general intelligence faster than conventional science remains to be seen, but this list of blogs provides great pointers for following progress. Thanks to Alba Collazo, Co-founder, Clinical Research Blog, for notifying us of Nanodot’s inclusion in their list and for bringing this resource to our attention.

Those attracted to the idea of Open Science may also want to check out the web site for Open Access Week, just ending. From the web site:

Open Access Week, a global event now entering its fourth year, is an opportunity for the academic and research community to continue to learn about the potential benefits of Open Access, to share what they’ve learned with colleagues, and to help inspire wider participation in helping to make Open Access a new norm in scholarship and research.

“Open Access” to information – the free, immediate, online access to the results of scholarly research, and the right to use and re-use those results as you need – has the power to transform the way research and scientific inquiry are conducted. It has direct and widespread implications for academia, medicine, science, industry, and for society as a whole.

Open Access (OA) has the potential to maximize research investments, increase the exposure and use of published research, facilitate the ability to conduct research across available literature, and enhance the overall advancement of scholarship. Research funding agencies, academic institutions, researchers and scientists, teachers, students, and members of the general public are supporting a move towards Open Access in increasing numbers every year. Open Access Week is a key opportunity for all members of the community to take action to keep this momentum moving forward.

On a purely personal note, French statesman Georges Clemenceau is reputed to have said something like “War is too important to be left to the generals.” Having watched progress in nanotechnology and artificial general intelligence since 1986, I am inclined to agree with the open science movement that progress in science in general, and nanotechnology and AGI in particular, is too important to be left solely to the professionals and the governments and large corporations that fund them.