Don's Review: Law, Politics, Science, Philosophy

March 6, 2010

If anyone should doubt that the U.S. is now a totalitarian state, he or she should go back a few weeks to that great American cultural spasm called the Super Bowl. As most of us watched it via comfortable sofas in our living rooms, the tens of thousands in the stadium watched while being watched.

            The power of the federal, state and city governments to monitor gatherings of U.S. citizens, whether at a harmless football game on the pretext of preventing a terrorist attack or outside city hall or on the Capitol Mall protesting nonextension of unemployment benefits has grown by leaps and bounds since the raucous 1960s, when protestors regularly marched on Washington.

            If you think the gadgets demonstrated on popular TV shows such as “NCIS” or “24” are demonstrations of TV writers’ imaginations, you are wrong. As everyone knows, President Obama can survey our phone calls and Internet usage at will, with Congress’ blessing. But that’s just the beginning.

To better coordinate and centralize information for Super Bowl XLIV, the Miami-Dade Police Department's Fusion Center deployed "Project Dolphin" with technology and tools from Microsoft and other partners.

The initiative used the department's existing Fusion Center, an office that collects crime reports about suspicious activities and analyzes them for terrorist threats.

“Many existing information-sharing systems were developed before today’s information-exchange standards like the National Information Exchange Model,” said Wes Anderson, vice president of U.S. Public Sector Services at Microsoft. “With these advanced fusion solutions, the work of local law enforcement experts can be improved through the better integration of standards, authentication and information sharing, even among historically siloed organizations.”

Fusion Core Solution was developed to strengthen the ability of government to prepare for large-scale events and improve local public safety efforts to prepare for and manage natural disasters. “The MDPD fusion project represents one of the best examples of collaboration on many levels,” said James Northern, vice president of Public Sector Strategic Business Development at Analyst International Corp. “The result of this completed solution adds another tool to help provide protection for our highest-profile and national events.”

More information about Fusion Core Solution from Microsoft and ESRI is available at http://www.microsoft.com/fusion.

Fusion centers cropped up all over the country as a result of the 9/11 Commission Act of 2007 to solve communications problems experienced by emergency responders and intelligence agencies that came to light after Sept. 11, 2001. The 9/11 Commission noted that there were plenty of warnings that an attack was imminent, but because of the way intelligence experts such as the FBI kept information in "silos," nobody connected the dots that might have warned us of the incoming threat.

"Project Dolphin" optimized information technology tools from Microsoft, ESRI, GuideSTAR Technologies and Analyst International Corporation (AIC) to enhance current real-time capabilities for intake, analysis and dissemination of actionable data from local, state, national justice and public safety officials responsible for securing Super Bowl XLIV, according to Microsoft.

Project Dolphin eased immediate, enhanced information sharing and collaboration, reduced the duplication of effort, improved situational awareness, expanded predictive and responsive analytics, as well as supported more thorough and comprehensive investigations. It also provided managers real-time oversight capability of case and incident management, tracking, and reporting.

Intelligence personnel in the past have often had a hard time working with massive amounts of information to organize, analyze and distill meaningful and usable intelligence. Without access to effective intake, analysis and dissemination of information from sources and partners, it has been difficult to identify patterns, trends and relevant relationships among various data sources.

Project Dolphin incorporated the Microsoft and ESRI-developed Fusion Core Solution, which integrates Microsoft SharePoint and ESRI's ArcGIS 9.3.1 server with GuideSTAR's investigative and intel-analysis tool GS/1. The combined technologies enhance the power of instant collaboration and information sharing among analysts and investigators while giving supervisors continual oversight.

When the Colts and Saints squared off each epitomized the concept of teamwork in their quest for the NFL’s championship. The teams within the event's video surveillance system were Aware Digital, Sony Electronics Security Systems Group and the Miami-Dade Police Department (MDPD) Homeland Security Section, in conjunction with the FBI and Miami Dade County Fire Department. The systems integrator, manufacturer and first responders deployed the best possible solution to ensure smooth operations.

The project necessitated a keen blend of technology and coordination.

Video from many different sources, including analog, IP PTZs, microwave, mast-mounted cameras and more, was consolidated and distributed to many different locations and in many different formats such as Mac, PC, flash, iPhone, etc. Aware Digital provided solutions to not only distribute these feeds but also to bring in additional outside feeds from other agencies and devices.

The project entailed digitally encoding the stadium's existing analog cameras, converting them into IP and adding standard and high definition (HD) IP pan/tilt/zoom (p/t/z) and rapid deployment cameras using wireless transmission. These cameras were augmented by the venue's approximately 200 existing IP cameras. It was critical to bring all the feeds into a centralized video management system (VMS) so everything that transpired was readily available for live viewing and/or review by stadium security, MDPD and other responders and emergency management agencies.

That awareness helped authorities mitigate anything and everything from crowd control to potential terrorist activity.

The site for the Super Bowl was selected four years in advance, and groundwork for the security component was laid out soon thereafter.

For Aware Digital, a big part of its success can be attributed to relationship building. In this case, it is something the security contractor had been cultivating with MDPD for some time, having provided equipment and services several times prior.

"We have worked with Aware Digital for more than two years now. They have always helped me out whenever I needed anything for other events such as the Miami Dade County Youth Fair," says Detective Juan "Johnnie" Villalobos, a 23-year veteran of the force who is coordinating the department's surveillance system efforts for this event.

According to the company, it has recently seen a particularly strong opportunity in collaborating with law enforcement to leverage advanced security solutions as a means to fortify crime-fighting efforts.

In addition to having its finger on the pulse of law enforcement, Aware Digital has established a track record of providing services for large-scale events involving as many as 100,000 or more people. Among the firm's recent credits are the NASCAR Championship in Homestead, Fla., Wings over Homestead Air Force Air Show and National Mayor's Conference.

In a nutshell, the mission was to design a solution that would provide the best quality and highest frame rate to all the agencies involved in the most flexible and efficient manner possible. To achieve this, the integrator and end user selected Sony IP cameras and digital encoders, OnSSI's VMS platform and recording software, with BridgeWave Communications supplying some of the wireless gear. The FBI, however, was using a Milestone VMS.

As it does on many projects of this scope, Sony worked closely with Aware Digital and MDPD to provide technical expertise and consultation. The project incorporates SNC-RH164 HD IP p/t/z cameras, SNC-RX550 standard definition (SD) IP p/t/z cameras and SNT Series SD IP video encoders.

Among other features, the integrator and end user were impressed with the equipment's video quality and real-time frame rate of 30 images per second.

"Our new HD p/t/z cameras being deployed at Dolphin Stadium incorporate proprietary Sony technologies such as XDNR dynamic noise reduction and Visibility Enhancer for scene contrast optimization," says Miguel Lazatin, senior marketing manager for Sony's Security Systems Group. "Combined they improve overall picture quality, increase sensitivity and make scenes more visible, especially in low light. These technologies and 10x optical zoom of our SNC-RH164 HD cameras are extremely critical when capturing incidents at long distances, and in densely populated environments such as the Super Bowl."

The stadium's expanded surveillance system is a semi-permanent installation that allows for quick deployment, removal and redeployment as needed for future events. As such, cabling and mounting equipment is permanently installed and select cameras are added when warranted.

Crowd Control Is Critical

The parking and general public areas surrounding Dolphin Stadium as well as multiple traffic spots were covered by the IP p/t/z cameras. Selected cameras from the venue's interior were integrated via multiple microwave downlinks that flow into encoders to be redistributed, with some feeds routed to mobile devices and even helicopters. In addition, the live game TV feed was integrated into the surveillance/situational awareness platform.

The system was monitored from a command vehicle and multiple other agencies during the Pro Bowl and Super Bowl events and connected back to the stadium cameras using a gigabit millimeter wave wireless link by BridgeWave Communications.

The installation itself required placing cameras where they could provide the best possible vantage points for monitoring the tens of thousands of fans, VIPs, facility staff, vendors and the teams and associated personnel. This meant mounting them in some extreme locations, including on top of the scoreboards.

"The NFL was very concerned about crowd control. They wanted to make sure that people making it to the Super Bowl get there as quickly and as safely as possible," says Villalobos. "There is a tailgate party between 1 p.m. and 5 p.m. that's also an event where we needed to get people inside as quickly as possible."

Aware Digital is making sure MDPD is thoroughly trained on operating the sophisticated surveillance solution well before the big game. Villalobos was excited about the system's capabilities and eager to take full advantage of them.

"Sony covered all the features that we would use and what we would need," he says. "Their cameras provide an analog and an IP option, which is a big plus. I also like features like day/night, being able to put the cameras on a schedule, the ability to zoom in, the aspect ratio, remote monitoring; it's just got so many great capabilities. And HD for security is amazing, especially for identifying people."

Surveillance Part of Bigger Picture

It has been demonstrated time and time again that the most effective security involves a layered approach encompassing many different but well coordinated practices and systems. It's all those vital pieces that add up to create a truly comprehensive solution. As such, video surveillance was only one aspect of the Super Bowl's multipronged plan.

"The stadium had intensive security checks as fans entered. Women could bring in their purses but there are no umbrellas, no backpacks, etc.," says Villalobos, who worked with the NFL on previous Super Bowls in Miami. "All delivery trucks were thoroughly searched and their drivers screened."

That truck screening area will be equipped with three Sony cameras to capture license plates and an overview of the parking area.

Ultimately, some instances of drunk and disorderly conduct, fights, theft and the like have to be anticipated in and around a scene such as the Super Bowl. However, the enacted measures should keep them to a minimum and lessen their severity. Beyond that, the “fusion” team members were told that it was of the utmost importance to be on high alert and ready to swing into immediate action should greater threats arise.

Feb. 21, 2010

CAIRO — The increasing production of biofuels is causing hundreds of millions of poor people around the world to go hungry, international relief group ActionAid has warned.

"Biofuels are driving a global human tragedy," researcher Tim Rice wrote in a new major report cited by The Guardian on Monday, February 15.

"Local food prices have already risen massively. As biofuel production gains pace, this can only accelerate."

Biofuel, also called agrofuel, is the fuel derived from recently dead biological material, most commonly plants.

Using arable land to produce crops for biofuel has reduced surfaces available to grow food worldwide.

The new report, themed "Meals per gallon: the impact of industrial biofuels on people and global hunger", cautioned that if global biofuel targets are met food prices could rise by up to an additional 76 percent by 2020.

It stressed that this will lead to an extra 600 million people going hungry.

"Poor people can spend as much as 80 percent of their income on food," Rice said.

"Even small increases in the price of staples such as maize and wheat mean that many more will become increasingly desperate."

World Bank estimates that food prices rose by 140 percent between 2002 and February 2008.

Biofuels have been accounted for a 75 percent of the increase, it said.

According to the UN Food and Agriculture Organization's world food index, dairy prices rose nearly 80 percent and grain 42 percent in 2007 alone.

With raging violent protests and fears of social discontent, many countries strained their budgets to maintain huge food subsidies.

Disastrous

ActionAid warned that the 2008 decision by EU countries to obtain 10 percent of all transport fuels from biofuels by 2020 is proving disastrous for poor countries.

"To meet the EU 10 percent target, the total land area directly required to grow industrial biofuels in developing countries could reach 17.5m hectares, over half the size of Italy," said the report.

"Additional land will also be required in developed nations, displacing food and animal feed crops onto land in new areas, often in developing countries."

The aid organization warned that meeting European biofuel targets could lead to an increase in hungry people by 100 million.

In the US, the biggest biofuel producer and consumer the situation is worse.

Analysis of US farm data last month by the Earth Policy Institute in Washington showed that one-quarter of all the maize and other grain crops grown in the US now ends up as biofuel in cars.

The grain grown to produce the fuel in the US in 2009 was enough to feed 330 million people for one year at average world consumption levels.

ActionAid also highlighted the negative impact of biofuels on climate change.

"Most biofuels are worse than the fossil fuels they are supposed to replace," said Rice.

The majority of biofuels need nitrogen fertiliser, releasing nitrous oxide, a greenhouse gas 300 times more damaging than carbon dioxide.

Scientists believe that the extent of nitrous oxide emissions has been seriously underestimated.

Scientists predict that average temperatures will rise by between 1.8 and 3.0 degrees Celsius this century because of greenhouse gas emissions, mainly from burning fossil fuels, causing floods and famines while putting millions of lives at risk.

Read more: http://www.islamonline.net/servlet/Satellite?c=Article_C&cid=1265890379481&pagename=Zone-English-News/NWELayout#ixzz0feB3XYHB

Feb. 21, 2010

Some people believe a future planet full of microscopic machines and microscopic agents in food or packaging could be a good thing. Nanobots might save countless lives in surgery, nanopackaging could make food cheaper and last longer, feeding millions.

But like any new technology, there may be risks. According to Wikipedia, ‘nanotech’, is the study of the controlling of matter on an atomic and molecular scale. Generally nanotechnology deals with structures of the size 100 nanometres or smaller in at least one dimension, and involves developing materials or devices within that size.’

Many such advances are taking place in packaging, food science, renewable sciences and medicine, even in your kitchen cleaning product. And there may be really exciting things on the horizon. Greenpeace’s media blogs report on changes where ‘self powered nanotechnology combined with textile fibres could turn a t shirt into a charging device. The fibres embedding in clothing would be powered by movement.’

Other companies like Solar Botanic are developing artificial trees and nanoleaves. ‘To complete the tree for multi energy exploitation, the petiole twigs and branches are incorporated with Nano piezo electric elements.” reveals their website.

‘A Nanoleaf is thin like a natural leaf, when outside forces, like the wind, push the Nanoleaf back and forth, mechanical stresses appear in the petiole, twig and branches. When thousands of Nanoleaves flap back and forth due to wind, millions and millions of pico watts are generated, the stronger the wind, the more energy is generated.’

‘Biomimicry is an emerging science resolving human problems by adopting nature’s processes. Using biomimicry techniques, a SolarBotanic artificial tree, or plant structure functions as a passive solarwind harvester. Ultimately, energy is harvested then efficiently captured, concentrated, stored and converted to a high value energy form.’ continues the press release.

Other designs include nanoengineered ‘intelligent paints’, which can resist rust, or have other altered properties making them resistant to graffiti. The list of potential applications seems endless.

Brave new world

Fabiana Batista works for Cargill Media Relations. Cargill, a corporate international, recently launched, ‘TopScreen DS13, a product made mainly from vegetal sources, which when applied on a paper surface results in a resistant water proof barrier. The product is an alternative for polyethylene, paraffin and acrylic resin, products derived from mineral oil and that are currently used for similar applications.’ The idea might be used in packaging to save fossil based alternatives, waterproofing the inside of your lunchtime sandwich box.

“Nanotechnology has enabled us to tune surface properties at the nanolevel.” explains Batista. “More specifically the combination of the mastering nanoroughness, mastering chemical composition of the nanoparticle and thermal curing of the coating defines the degree of the super hydrophobic aspect of this biopolymer.”

“Depending on the type of substrate we can adapt the product to have an optimum nanoroughness and chemical composition to obtain the highest degree of water repellency.”

“Any cardboard or paper packaging that is submitted to condensation or liquids is an application for this product. Countries for example with high humidity that produce, transport and consume fruit, vegetables or fish are an interesting market. As Brazil is an emerging market, eager for ecological innovation, producing a lot of cardboard for fresh food packaging; we decided to enter this market first.”

Other places like Cornell University have been working on nanocomposites, and bio inspired nanostructures, many of which again might have potential uses in packaging or medicine and food. More excitingly, recent news releases explain Georgia Institute of Technology may have found how nanotechnology can fight cancer:

“We have previously shown that superparamagnetic nanoparticles conjugated to an ephrin A1 mimetic peptide with a high affinity for the EphA2 receptor can be used to capture and remove cultured human ovarian cancer cells from the peritonea of experimental mice.” explains the abstract from http://www.nanomedjournal.com/

Running scared

And this is where some people begin to get frightened. ‘The UK Lords science and technology committee is urging the government and research councils to carry out more checks into the use of nanomaterials in food and in particular the dangers for the human body,’ explains The Soil Association. (SA)

“You can argue that the GMO is removed at the fermentation stage and that as such packaging itself contains no GM. But the fact is that the genetic engineering process is very messy biologically and many other genes get modified in the process, so new biochemicals are produced. Some of these may be toxic.” explains the Association’s Gundula Azeez.

GM is not identical science to nanotech, but many similar arguments apply. From January 2008, the Soil Association in the UK banned the use of nanomaterials in products wishing to claim its organic certification. The risk may be particularly high in food, packaging or medicine, where we directly ingest the new science.

Some people are worried nanotechnology can cross boundaries and transmutate in the body. And very little real testing has been done to assess such dangers.

“There’s not been a huge amount of concrete development in this area recently, something significant is that the EU is funding Professor Vivian Howard to research a programme assessing the dangers of nanotech in food.” continues Peter Melchett, who heads up work on nanotech for the SA.

“There has been talk and discussion of research in animals which has suggested that these nanotech elements may have the ability to cross through the blood/brain barrier, there have been select committees set up to investigate this, every serious scientific body is saying lets not commercialise if we can’t guarantee whether there are any true theoretical risks, but the EU commission seems to be about the only body worldwide which is actually funding work to find all this out.”

“We know the brain is normally protected from materials in the blood to prevent them acting as external influencers, so the risk of toxicity and cell functions, though unproven, needs to be researched, Alzheimer’s is the kind of threat you may see as a result of influence on brain function.”

“We just need to be sure we don’t make the same mistake as GM, charging ahead with industry, there is talk of nanotech in things like clothing, then again it’s hard to know how much of this is marketing and how much of it is actual nanotech science.”

Melchett wants to see consistent safety checking done, hopefully responsible companies will do this anyway. The issue is also that while everyone agrees in theory more testing is needed, this is not a headline issue so it’s low on global government agendas.

“It makes sense to observe a precautionary principle, and wait for the testing to show us the way forward. If you look at GM, the first people to ban GM soya were Mitsubishi, and Heinz banned GM tomatoes. Japan, Western Europe, India and China all followed or are following suit.” he continues.

“But in the US people don’t know they’re eating GM, so there’s little disquiet there. Then again, GM free is the fastest growing health brand in the US at 67 per cent.”

“So the point is as people become aware so markets have to react in the same way, where Monsanto was forced to concede when the GM hormone milk situation occurred, where the EU wouldn’t take it so the US began to apply trade sanctions against Dijon mustard. Let’s have an informed debate on the safety.”

For some, it may be too late. ‘Over 1,000 nanotechnology enabled products have been made available to consumers around the world,’ reveals the Project on Emerging Nanotechnologies (PEN). So if there is a risk, it’s already at large in the ecosystem.

‘The most recent update to the group’s three and a half year old inventory reflects the increasing use of the tiny particles in everything from conventional products like non stick cookware and lighter, stronger tennis racquets, to more unique items such as wearable sensors that monitor posture.’ Apparently 90 per cent of Americans want better public information on this.

‘Existing health and safety agencies are unable to cope with the risk assessment, standard setting and oversight challenges of advancing nanotechnology.’ reckons PEN 18 - Oversight of Next Generation Nanotechnology.

The horse has probably already bolted.

Taken From Our Future Planet Web site.

Dec. 31, 2009

It was hard for me to accept my own atheism after the death of my father in 2006. As I’ve written elsewhere, many factors stood in the way.

But atheism always was in the back of my mind. As a 15-year-old, I told my mother that I only went to church “to socialize.” Since age 6 or 7, I had pondered the lack of logic in the concept of the “Holy Trinity” or three persons in one, and the “Immaculate Conception” by the “Virgin” Mary. I accepted them because the stewards of those fairy tales were my elders, within my own family and the pasty-faced, 60-something virginal old men who wore those impressive pointed hats at my Catholic churches.

As the years went on, the countering questions emerged. Perhaps, it was “There must be more than just this” to the world (sunsets, flowers, sex). Then it may have been: “How could something this complex be created without a supreme being. How could a watch be created without a wise watch craftsperson?”

Then, I personally experienced accidents and the moral neutrality of the world (previously explained away in books entitled, “Why Bad Things Happen to Good People”). And, from my colleagues and readings, I heard: “Well, San Francisco is complicated and beautiful, but it was built clear across barren prairies, bit by bit, by millions of accidents and by no single mastermind.”

And, I heard about the flagellum motor which helped our single-cell forebearers connect to each other via a rotating tail (like a snake swimming) and build themselves into larger entities via pulling building materials up a column inside a tail by polarity changes so that those materials could be placed on top, simply because the materials’ molecules had the right shape to fit on top. Our single-cell ancestors also had been formed by simple chemistry: “Let’s form a circle and trap this fellow inside.” “How do we do that?” “Simple idea: See a need, fill a need. If there are a lot of us, this must be a good place to make a shelter.” “How’d this concentration of us come about?” “Entropy, stupid!” or “Polarity, stupid!”

And, atheism became easier for me. I overcame the “child abuse” (if you believe Richard Dawkins, and I do) of tender minds fed illogical tales and false dreams and hopes that lead them to pursue unrealistic goals or strive to be perfect so the wrath  of god doesn’t get them when  they die. So much idiotic malfeasance, abuse, and torturous war has been propounded based on those tales and dreams. What a nightmare! And it continues. In Afghanistan, in our homes, within our families, between friends, in Yemen, etc. Ugh!

The bacterial flagellum is one of the most striking organelles found in biology. In Escherichia coli the flagellum is about 10 μm long, but the helical filament is only 20 nm wide and the basal body about 45 nm wide. The flagellum is made up of approximately 20 major protein parts with another 20-30 proteins with roles in construction and taxis (Berg, 2003; Macnab, 2003). Many but not all of these proteins are required for assembly and function, with modest variation between species. Over several decades, thousands of papers have gradually elucidated the structure, construction, and detailed workings of the flagellum. The conclusions have often been surprising.

Berg and Anderson (1973) made the first convincing case that the flagellar filament was powered by a rotary motor. This hypothesis was dramatically confirmed when flagellar filaments were attached to coverslips and the rotation of cells was directly observed (Silverman and Simon, 1974). The energy source for the motor is proton motive force rather than ATP (Manson et al., 1977). ATP is an abbreviation for adenosine triphosphate, a complex molecule that contains the nucleoside adenosine and a tail consisting of three phosphates.

The flagellar filament is assembled from the inside out, with flagellin monomers added at the distal tip after export through a hollow channel inside the flagellar filament (Emerson et al., 1970). The flagella of E. coli rotate bidirectionally at about 100 Hz, propelling the rod-shaped cell (dimensions 1x2 μm) 10-30 μm/sec. The flagella of other species, powered by sodium ions rather than hydrogen ions, can rotate at over 1500 Hz and move cells at speeds of several hundred μm/sec. The efficiency of energy conversion from ion gradient to rotation may approach 100% (DeRosier, 1998). The bacterial flagellum is now one of the best understood molecular complexes, although numerous detailed questions remain concerning the function of various protein components and the exact mechanism of torque generation. However, the origins of this remarkable system have hardly been examined. This article will propose a detailed model for the evolutionary origin of the bacterial flagellum, along with an assessment of the available evidence and proposal of further tests. That the time is ripe for a serious consideration of this question is discussed below.

Biologists find it almost inescapable to compare the bacterial flagellum to human designs: DeRosier remarks, “More so than other structures, the bacterial flagellum resembles a human machine” (DeRosier, 1998). The impression is heightened by electron micrograph images reminiscent of a engine turbine (e.g., Whitesides, 2001), and the scientific literature on the flagellum is filled with analogies to human-designed motors. There is no shortage of authorities willing to express mystification on the question of the evolutionary origin of flagella. In a 1978 review, Macnab concluded,

As a final comment, one can only marvel at the intricacy, in a simple bacterium, of the total motor and sensory system which has been the subject of this review and remark that our concept of evolution by selective advantage must surely be an oversimplification. What advantage could derive, for example, from a “preflagellum” (meaning a subset of its components), and yet what is the probability of “simultaneous” development of the organelle at a level where it becomes advantageous?” (Macnab, 1978).

The basic puzzle is that the flagellum is made up of dozens of protein components, and deletion experiments show that the flagellum will not assemble and/or function if any one of these components is removed (with some exceptions). How, then, could this system emerge in a gradual evolutionary fashion, if function is only achieved when all of the required parts are available?

The bacterial flagellum is a complex molecular system with multiple components required for functional motility. Such systems are sometimes proposed as puzzles for evolutionary theory on the assumption that selection would have no function to act on until all components are in place. Previous work (Thornhill and Ussery, 2000, A classification of possible routes of Darwinian evolution. J Theor Biol. 203 (2), 111-116) has outlined the general pathways by which Darwinian mechanisms can produce multi-component systems. However, published attempts to explain flagellar origins suffer from vagueness and are inconsistent with recent discoveries and the constraints imposed by Brownian motion.

A new model is proposed based on two major arguments. First, analysis of dispersal at low Reynolds numbers indicates that even very crude motility can be beneficial for large bacteria. Second, homologies between flagellar and nonflagellar proteins suggest ancestral systems with functions other than motility. The model consists of six major stages: export apparatus, secretion system, adhesion system, pilus, undirected motility, and taxis-enabled motility. The selectability of each stage is documented using analogies with present-day systems. Conclusions include: (1) There is a strong possibility, previously unrecognized, of further homologies between the type III export apparatus and F₁F₀-ATP synthetase. (2) Much of the flagellum’s complexity evolved after crude motility was in place, via internal gene duplications and subfunctionalization. (3) Only one major system-level change of function, and four minor shifts of function, need be invoked to explain the origin of the flagellum; this involves five subsystem-level cooption events. (4) The transition between each stage is bridgeable by the evolution of a single new binding site, coupling two pre-existing subsystems, followed by coevolutionary optimization of components. Therefore, like the eye contemplated by Darwin, careful analysis shows that there are no major obstacles to gradual evolution of the flagellum.

Archaeal

The archaeal flagellum is superficially similar to the bacterial (or eubacterial) flagellum; in the 1980s they were thought to be homologous on the basis of gross morphology and behavior. Both flagella consist of filaments extending outside of the cell, and rotate to propel the cell. Archaeal flagella have a unique structure which lacks a central channel. Similar to bacterial type IV pilins, the component flagellins are made with class 3 signal peptides and they are processed by a type IV prepilin peptidase-like enzyme. The archaeal flagellins are typically modified by the addition of N-linked glycans which are necessary for proper assembly and/or function.

Discoveries in the 1990s revealed numerous detailed differences between the archaeal and bacterial flagella; these include:

* Bacterial flagella are motorized by a flow of H⁺ ions (or occasionally Na⁺ ions); archaeal flagella are almost certainly powered by ATP. The torque-generating motor that powers rotation of the archaeal flagellum has not been identified.

* While bacterial cells often have many flagellar filaments, each of which rotates independently, the archaeal flagellum is composed of a bundle of many filaments that rotate as a single assembly.

* Bacterial flagella grow by the addition of flagellin subunits at the tip; archaeal flagella grow by the addition of subunits to the base.

* Bacterial flagella are thicker than archaeal flagella, and the bacterial filament has a large enough hollow "tube" inside that the flagellin subunits can flow up the inside of the filament and get added at the tip; the archaeal flagellum is too thin to allow this.

Many components of bacterial flagella share sequence similarity to components of the type III secretion systems, but the components of bacterial and archaeal flagella share no sequence similarity. Instead, some components of archaeal flagella share sequence and morphological similarity with components of type IV pili, which are assembled through the action of type II secretion systems (the nomenclature of pili and protein secretion systems is not consistent).

These differences could mean that the bacterial and archaeal flagella could be a classic case of biological analogy, or convergent evolution, rather than homology. However, in comparison to the decades of well-publicized study of bacterial flagella (e.g. by Berg), archaeal flagella have only recently begun to get serious scientific attention. Therefore, many assume erroneously that there is only one basic kind of prokaryotic flagellum, and that archaeal flagella are homologous to it. For example, Cavalier-Smith (2002) is aware of the differences between archaeal and bacterial flagellins, but retains the misconception that the basal bodies are homologous.

Structure

A eukaryotic flagellum is a bundle of nine fused pairs of microtubule doublets surrounding two central single microtubules. The so-called "9+2" structure is characteristic of the core of the eukaryotic flagellum called an axoneme. At the base of a eukaryotic flagellum is a basal body, "blepharoplast" or kinetosome, which is the microtubule organizing center (MTOC) for flagellar microtubules and is about 500 nanometers long. Basal bodies are structurally identical to centrioles. The flagellum is encased within the cell's plasma membrane, so that the interior of the flagellum is accessible to the cell's cytoplasm.

Mechanism

Each of the outer 9 doublet microtubules extends a pair of dynein arms (an "inner" and an "outer" arm) to the adjacent microtubule; these dynein arms are responsible for flagellar beating, as the force produced by the arms causes the microtubule doublets to slide against each other and the flagellum as a whole to bend. These dynein arms produce force through ATP hydrolysis. The flagellar axoneme also contains radial spokes, polypeptide complexes extending from each of the outer 9 microtubule doublets towards the central pair, with the "head" of the spoke facing inwards. The radial spoke is thought to be involved in the regulation of flagellar motion, although its exact function and method of action are not yet understood.

Difference of beating pattern of flagellum and cilia

Though eukaryotic flagella and motile cilia are ultrastructurally identical, the beating pattern of the two organelles can be different. In the case of flagella (e.g. the tail of a sperm) the motion is propeller-like. In contrast, beating of motile cilia consists of coordinated back-and-forth cycling of many cilia on the cell surface. Thus, flagella serve for the propulsion of single cells (e.g. swimming of protozoa and spermatozoa), and motile cilia for the transport of fluids (e.g. transport of mucus by stationary ciliated cells in the trachea). However, cilia are also used for locomotion (through liquids) in organisms such as Paramecium.

Intraflagellar Transport

Intraflagellar transport (IFT), the process by which axonemal subunits, transmembrane receptors, and other proteins are moved up and down the length of the flagellum, is essential for proper functioning of the flagellum, in both motility and signal transduction.

Evolution of flagella and debate

Based on similarity in structure and partial similarity in amino acid sequence, it is generally accepted among scientists that the eukaryotic flagellum and cillium have evolved from the cytoskeleton, while the eubacterial flagellum has evolved either from the type III secretion system or from a more ancient secretion system from which the type III secretion system has evolved as well. The archeal flagellum has probably evolved from the type IV pili.

In his 1996 book Darwin's Black Box, intelligent design proponent Michael Behe cited the bacterial flagellum as an example of an irreducibly complex structure that could not have evolved through naturalistic means. Behe argued that the flagellum becomes useless if any one of its constituent parts is removed, and thus could not have arisen through numerous, successive, slight modifications; therefore, it is hopelessly improbable that the proteins making up the flagellar motor could have come together all at once, by chance. Mark Perakh explained that while Behe popularized the idea, biologist Hermann J. Müller had already explored it (under the slightly different name of “interlocking complexity”) and more than a decade before Behe’s book the same idea was explored by A. Graham Cairns-Smith, but neither claimed that “irreducible complexity” was a “marker” of a supernatural design.

While Behe discussed the immune system and the blood clotting cascade in greater detail, the bacterial flagellum has become a "poster child" for intelligent design proponents and other creationists. It is one of two identified rotary structures found in nature (the other being ATP synthase) and it is billions of years older than Behe's other two examples, which exist in many homologous forms, simplifying the explanation of their origin.

Evolutionary pathways supported by the Theory of Natural Selection and Evolution (see: "The Flagellum Unspun and PBS/Nova Science's television production of Intelligent Design on Trial) have since been identified for the bacterial flagellum; thus, undermining Behe's argument. In addition, the Type three secretion system, a molecular syringe which bacteria use to inject toxins into other cells, appears to be a simplified sub-set of the bacterial flagellum's components, meaning that it is much less likely to be irreducibly complex in the way that the bacterial flagellum could have in fact evolved from the type three secretion system.

Exaptation explains how systems with multiple parts can evolve through natural means.

Exaptation, cooption, and preadaptation are related terms referring to shifts in the function of a trait during evolution. For example, a trait can evolve because it served one particular function, but subsequently it may come to serve another. Exaptations are common in both anatomy and behavior. Bird feathers are a classic example: initially these evolved for temperature regulation, but later were adapted for flight. Interest in exaptation relates to both the process and product of evolution: the process that creates complex traits and the product that may be imperfectly designed.

 History and definitions

The idea that the function of a trait might shift during its evolutionary history originated with Charles Darwin (1859, ch. 6). For many years the phenomenon was labeled "preadaptation." Unfortunately, the term suggests forethought, which is contrary to a basic principle of natural selection.

The idea had been explored by several scholars when in 1982 Gould and Vrba introduced the term "exaptation". Unfortunately for subsequent discussions, this definition had two categories with different implications for the role of adaptation.

(1) A character, previously shaped by natural selection for a particular function (an adaptation), is coopted for a new use—cooptation. (2) A character whose origin cannot be ascribed to the direct action of natural selection (a nonaptation), is coopted for a current use—cooptation. Gould and Vrba (1982)

The definitions are silent as to whether exaptations had been shaped by natural selection after cooption, although Gould and Vrba cite examples (e.g., feathers) of traits shaped after cooption.

To avoid these ambiguities, Buss, et al. (1998) suggested the term "co-opted adaptation," which is limited to traits that evolved after cooption. However, the commonly-used terms of "exaptation" and "cooption" are ambiguous in this regard.

Examples

There are many examples of exaptations. A classic example is feathers, which initially evolved as insulation, were co-opted for display, and eventually were co-opted for use in bird flight. Another example is the gas bladder of fish, which evolved from early lungs.

A behavioral example pertains to subdominant wolves licking the mouths of alpha wolves as a sign of submissiveness. (Similarly, dogs, which are domesticated wolves, lick the faces of their human owners.) This trait can be explained as an exaptation of wolf pups licking the faces of adults to encourage them to regurgitate food.

Implications

Evolution of complex traits

One of the challenges to Darwin's theory of evolution was explaining how complex structures could evolve gradually, given that their incipient forms may have been inadequate to serve any function. As Mivart (a critic of Darwin) pointed out, 5 percent of a bird wing would not be functional. The incipient form of complex traits would not have survived long enough to evolve to a useful form.

As Darwin elaborated in the last edition of On the Origin of Species, many complex traits evolved from earlier traits that had served different functions. By trapping air, primitive wings would have enabled birds to efficiently regulate their temperature, in part, by lifting up their feathers when too warm. Individual animals with more of this functionality would more successfully survive and reproduce, resulting in the proliferation and intensification of the trait.

Eventually, feathers became sufficiently large to enable some individuals to glide. These individuals would in turn more successfully survive and reproduce, resulting in the spread of this trait because it served a second and still more beneficial function: that of locomotion. Hence, the evolution of bird wings can be explained by a shifting in function from the regulation of temperature to flight.

Jury-rigged design

Darwin explained how the traits of living organisms are well-designed for their environment, but he also recognized that many traits are imperfectly designed. They appear to have been made from available material, that is, jury-rigged. Understanding exaptations may suggest hypotheses regarding subtleties in the adaptation. For instance, that feathers evolved initially for thermal regulation may help to explain some of their features unrelated to flight (Buss et al., 1998).

Some of the chemical pathways for physical pain and pain from social exclusion overlap (MacDonald and Leary, 2005). The physical pain system may have been co-opted to motivate social animals to respond to threats to their inclusion in the group.

The evolution of flagella is of great interest to biologists because the three known varieties of flagella (eukaryotic, bacterial, and archaebacterial) each represent an extremely sophisticated cellular structure that requires the interaction of many different finely-tuned systems.

The eukaryotic flagellum

There are two competing groups of models for the evolutionary origin of the eukaryotic flagellum (referred to as cilium below to distinguish it from its bacterial counterpart).

Symbiotic/endosymbiotic/exogenous models

These models argue some version of the idea that the cilium evolved from a symbiotic spirochete that attached to a primitive eukaryote or archaebacterium (archaea). The modern version of the hypothesis was first proposed by Lynn Margulis. The hypothesis, though very well publicized, was never widely accepted by the experts, in contrast to Margulis' arguments for the symbiotic origin of mitochondria and chloroplasts.

The primary point in favor of the symbiotic hypothesis is that there are eukaryotes that use symbiotic spirochetes as their motility organelles (some parabasalids inside termite guts, such as Mixotricha and Trichonympha). While this is an example of co-option and the flexibility of biological systems, none of the proposed homologies that have been reported between cilia and spirochetes have stood up to further scrutiny. The homology of tubulin to the bacterial replication/cytoskeletal protein FtsZ is a major argument against Margulis, as FtsZ is apparently found native in archaea, providing an endogenous ancestor to tubulin (as opposed to Margulis' hypothesis, that an archaea acquired tubulin from a symbiotic spirochete).

At present the symbiotic hypothesis for the origin of cilia seems to be limited to Margulis and a few of her associates. Margulis is, though, still strongly promoting and publishing a revised version of her hypothesis.

Endogenous/autogenous/direct filiation models

Contrasting with the symbiotic models, these models argue that cilia developed from pre-existing components of the eukaryotic cytoskeleton (which has tubulin and dynein – also used for other functions) as an extension of the mitotic spindle apparatus. The connection can still be seen, first in the various early-branching single-celled eukaryotes that have a microtubule basal body, where microtubules on one end form a spindle-like cone around the nucleus, while microtubules on the other end point away from the cell and form the cilium. A further connection is that the centriole, involved in the formation of the mitotic spindle in many (but not all) eukaryotes, is homologous to the cilium, and in many cases is the basal body from which the cilium grows.

An apparent intermediate stage between spindle and cilium would be a non-swimming appendage made of microtubules with a selectable function like increasing surface area, helping the protozoan to remain suspended in water, increasing the chances of bumping into bacteria to eat, or serving as a stalk attaching the cell to a solid substrate.

Regarding the origin of the individual protein components, an interesting paper on the evolution of dyneins shows that the more complex protein family of ciliary dynein has an apparent ancestor in a simpler cytoplasmic dynein (which itself has evolved from the AAA protein family that occurs widely in all archea, bacteria and eukaryotes). Long-standing suspicions that tubulin was homologous to FtsZ (based on very weak sequence similarity and some behavioral similarities) were confirmed in 1998 by the independent resolution of the 3-dimensional structures of the two proteins.

The bacterial flagellum

An approach to the evolutionary origin of the bacterial flagellum is suggested by the fact that a subset of flagellar components is similar to the Type III secretory and transport system.

All currently known nonflagellar Type III transport systems serve the function of injecting toxin into eukaryotic cells. It is hypothesised that the flagellum evolved from the type three secretory system. For example, the bubonic plague bacterium Yersinia pestis has an organelle assembly very similar to a complex flagellum, except that is missing only a few flagellar mechanisms and functions, such as a needle to inject toxins into other cells. It is also a possibility that the flagellum could have evolved from a currently undiscovered system with similar flagellar traits or a currently extinct organelle/organism. As such, the type three secretory system supports the hypothesis that the flagellum evolved from a simpler bacterial secretion system.

The archaeal flagellum

The recently elucidated archaeal flagellum is analogous, not homologous, to the bacterial one. In addition to no sequence similarity being detected between the genes of the two systems, the archaeal flagellum appears to grow at the base rather than the tip, and is about 15 nanometers (nm) in diameter rather than 20. Sequence comparison indicates that the archaeal flagellum is homologous to Type IV pili. (pili are filamentous structures outside the cell). Interestingly, some Type IV pili can retract. Pilus retraction provides the driving force for a different form of bacterial motility called "twitching" or "social gliding" which allows bacterial cells to crawl along a surface. Thus Type IV pili can, in different bacteria, promote either swimming or crawling. Type IV pili are assembled through the Type II transport system. So far, no species of bacteria is known to use its Type IV pili for both swimming and crawling.

Feb. 27, 2010

Two groups of Howard Hughes Medical Institute (HHMI) scientists working independently have identified a critical enzyme that allows the malaria-causing parasite, Plasmodium falciparum, to take over and thrive in human red blood cells. The enzyme plasmepsin V (PMV) is a gatekeeper inside the malaria parasite that allows the parasite to export its own proteins into a human red blood cell. Once PMV opens the gate into the red blood cell, the parasite moves hundreds of the proteins into cell, which remodels it and, eventually, annihilates it. The new observations demonstrate that PMV is critical to survival of the malaria parasite and suggest that drugs targeting PMV may be able to kill the parasite before it develops inside red blood cells.

This research was published by HHMI international research scholar Alan Cowman and HHMI investigator Daniel Goldberg in two articles in the February 4, 2010, issue of Nature.

James E. Keeley Jr., associate director of communications for HHMI, and Jennifer L. Michalowski, media relations specialist, did not return several emails or phone calls made to HHMI in Chevy Chase, Md.

When a malaria-carrying mosquito bites a human host, the malaria parasite enters the bloodstream, multiplies in the liver cells, and is then released back into the bloodstream, where it infects and destroys red blood cells.

A mosquito becomes infected with malaria when it sucks the blood from an infected human. Once inside the mosquito, the parasites reproduce in the gut and accumulate in the salivary glands, ready to infect another human host with the next bite.

A new vaccine tested in 100 West African children triggers the immune system to produce antibodies against the malaria parasite at levels normally seen only in adults who have strong resistance to the disease.

“We may have achieved our goal of producing with a vaccine a level of immunity that normally takes many years to develop,” said Christopher V. Plowe, a Howard Hughes Medical Institute (HHMI) investigator at the University of Maryland School of Medicine in Baltimore.

Based on its safety and strong immune response, Plowe and his collaborators are now testing the vaccine in 400 children to see whether it is effective in protecting them against malaria. The results will be submitted for publication later this year.

Plowe and a group of U.S. and Belgian collaborators from the Walter Reed Army Institute of Research, USAID and GlaxoSmithKline Biologicals have been developing and testing the vaccine with a large team of researchers led by Professors Ogobara K. Doumbo and Mahamadou A. Thera at the University of Bamako in Mali. The results of their phase I randomized controlled trial were published online in the February 4, 2010, issue of PLoS ONE, a journal of the Public Library of Science.

The malaria parasite, Plasmodium falciparum, is transmitted to humans by infected mosquitoes. When the mosquito bites, the parasite enters a person’s bloodstream and migrates to the liver. Inside liver cells, the parasite multiples and takes on a new form, called a merozoite, which is capable of infecting red blood cells. The clinical symptoms of malaria -- typically chills and fever -- occur as the merozoites burst from infected blood cells to infect other red blood cells and repeat the cycle.

Children in countries where malaria is endemic are particularly susceptible to the disease because they have not built up the levels of immunity found in adults who live in the same regions. More than 300 million cases of malaria occur each year, leading to more than one million deaths. More than 80 percent of those deaths occur among African children younger than age five. No approved vaccine is available to protect against the disease. Medications are available to treat malaria, but resistance to these drugs is a common problem that is worsening.

Plowe and his colleagues tested a vaccine that targets a molecule on the malaria parasite known as apical membrane antigen 1 (AMA1). The molecule sits on the surface of the merozoite form of the parasite and helps it invade red blood cells. The human immune system recognizes the presence of AMA1 molecules and generates antibodies that prevent invasion of red blood cells by the merozoites. But the body generates antibodies only after repeated exposure to malaria. If researchers could develop a vaccine that primes the immune system to recognize AMA1 before malaria infection occurs, it would be a major advance in the effort to control and eventually eradicate the disease.

In the trial, 100 healthy Malian children received either the vaccine or, as a control, a rabies vaccine. Some of the children experienced temporary pain and swelling at the site of the injections, but the effects were generally “well-tolerated,” according to Plowe.

Prior to receiving the vaccine, the children in the trial had only low levels of antibodies against AMA1 in their blood. Those antibody levels increased more than 100-fold in the children receiving the malaria vaccine and remained high during a year of follow-up blood tests. “The antibody levels that the vaccinated children achieved were as high or higher than those measured in adults whose lifelong exposure to malaria protects them against the disease,” said Plowe.

The study was funded by the National Institute of Allergy and Infectious Diseases and the United States Agency for International Development. The vaccine was invented and manufactured by the Walter Reed Army Institute of Research and formulated with an adjuvant -- a compound that boosts the immune response to the vaccine -- from GlaxoSmithKline Biologicals.

Based on its safety profile and strong immune response, Plowe and his U.S. and Malian collaborators are now testing the vaccine in 400 children. The results of the larger trial will shed light on a key uncertainty surrounding malaria vaccines. The AMA1 molecule occurs in many different forms both within Africa and around the world, and a vaccine against some forms of the molecule may not protect against other forms. “We want to know whether this vaccine, which is based on a single strain of the malaria parasite, can protect against the diverse array of wild parasites,” said Plowe.

Even if one vaccine does not protect against all strains of the parasite, a combination of vaccines could improve protection, Plowe adds. “If our next trial shows even partial protection, it would open the possibility that this vaccine can be combined with other vaccines to produce a next-generation, multi-component vaccine that is broadly protective,” said Plowe.

Dec. 21, 2009

The consensus among scientists is that humans evolved from their closest relatives, the bonobo chimpanzees about 200,000 years ago. About 20,000 years ago, our species, homo sapiens sapiens, appeared. Language developed 10,000 years ago. The Industrial Revolution came only 150 years ago. The entire universe is about 14 billion years old.

All that is hard enough for some people to digest, given their religious leanings, which say that the Earth was created about 4,000 years ago and humans instantly appeared as they do now in form and mental function.

But something else is even more difficult to grasp: Humans—and all life forms and conditions on Earth—are continuing to evolve. So much so that 20,000 years from now, our descendants likely will live as differently as we do from the first homo sapiens.

                Human beings mostly have a perception of time that stretches only from their great-grandparents (at most) to their great-grandchildren (at most). But the ongoing evolution of human beings is easy to grasp if one only observes the increased height and weight of humans just since 1776. Visit Monticello or Mount Vernon and you will see the smaller beds and forehead-banging door heights. You may also easily see how humans’ letter-writing abilities have disappeared since 1776. John Adams and Thomas Jefferson wrote 20-page letters with ease, while my family and I are lucky to get a two-sentence email off once a week to each other.

                It seems appropriate in Don’s Review to try to look at the cutting edge of human beings’ evolution. That is, where humans may be headed over the next 100, 1,000 or, even, 1 million years. This presumes, of course, that our species survives the multiple extinction-bearing catastrophes banging away at our doors!

                “Year Million: Science at the Far Edge of Knowledge,” as edited by Damien Broderick (Atlas & Co., New York, 2008), is a collection of 14 long essays written by scientific luminaries that include Sean M. Carroll (of evo-devo fame), Rudy Rucker, and Robert Bradbury. The authors, in easy-to-read prose, give their predictions for the fate of human beings in the year 1 million. There is, of course, no consensus when it comes to predictions of that magnitude.

                And the possibilities are endless even if working within the boundaries of today’s known physical and cosmological science—never mind the possibility that the most-famous physicist since Sir Isaac Newton, Albert Einstein, still is held dear in scientists’ hearts. But some of those same scientists already are fiddling with one of Einstein’s insights, that the speed of light is top speed in our universe.

                I chose to focus on one essay, by Steven B. Harris, “A Million Years of Evolution,” that combines elements of the others and seems a tiny bit more feasible. Harris is a geriatrician and internist and president and director of research at Critical Care Research, a company that grew out of 21st Century Medicine in Rancho Cucamonga, Calif.

But, as I said, with humans’ logarithmic, skyrocketing technological developments since the late 1800s, who knows? If we physically resemble ourselves at all in year 1 million, will we live a lifestyle recognizable to us in 2009? Doubtful. Humans only 10,000 years ago would be shocked to see our current bodies and lifestyles.

                Interestingly, the mushroom-like growth of the human brain over the last 1.5 million years—it has increased a third in mass while the rest of human anatomy changed only a little—resembles the peacock’s tail—a selection factor when females chose their mates.

                Even subtler changes can take place over time within the brain, in the software, so to speak. This “software” has become more important to our behavior, sexual or otherwise.

                Homo sapiens sapiens is now largely a software species, perhaps the first governed mainly by epigenetic factors (outside the genome), some of which are extrasomatic (outside the body). Much of what makes us special is stored not in genes or brains, but in libraries, laws, traditions, and songs.

                About 15,000 years ago, people started doing complicated tasks that must have taken a lot of group coordination. When writing arrived, brain size and memory were not so important. But writing opened the door to the final leap into the present day. It put the focus on a new form of culture, one dependent on information storage, in which most of the information is stored OUTSIDE the brain structure.

                Finally, when the computer arrived and shrank enough to fit into homes and then into the hand, suddenly common individuals gained digital access to ALL of human culture.

                Humanity began functioning with what we now call “parallel decentralized processing”—a process where nobody in particular is in charge, and there is no central control. That’s what some of our high culture is, a collection of intelligent “entities” constructed from multiple brains and data storage centers. For example, a modern city is beyond the mental capacity of any one person, but gets built anyway via the collaboration of thousands of engineers and devices. Those megaprojects already have depended on a form of “artificial intelligence.”

                Harris asks, “Does it matter whether or not SOME of the total processing is still done organically?” That fraction done by brains will finally become irrelevant when the distinction between processing organically and electronically disappears. And it will.

                At some point in the 21^st century, information will be processed by manipulating spins of individual electrons on appropriate electronic “devices.” Some number, says Harris, “I won’t guess how many, but I think it will be attainable like a million or a billion” will equal the processing power of a human neuron. A neuron itself contains about five hundred trillion atoms. At some point, “it will be possible to replace any given neuron with its electronic equivalent. Then more of  them. Then finally, ‘why not?’ all of them,” he says.

                Even before that time, however, it should be possible to connect neurons to neurons OUTSIDE  their native brains. At some point, mechanical telepathy will be possible. “Imagine being able to remember the entire contents of our digitized civilization with the same ease you remember basic spelling,” Harris says. “Now imagine being able to do that trick with SELECTED memories from ANOTHER human being.” But suppose you did? Harris asks. “How much of the other person would remain ‘in you,’ as part of you and vice versa? That would depend on how good your file copy system is.”

                Harris continues, “You could even give these borrowed memories permission to influence your unconscious actions. You would then acquire not only something of the other person’s memories, but also the other’s intuitions, judgement, anxieties, and passions. Already, people in a long, close relationship often know what the other is going to say.”

                “Now, imagine drawing in other minds,” Harris queries. “The result is the Internet [on steroids]: direct brain-to-brain connection, amplified by computerized search and processing help.”

                Without having to wait generation by generation for better brain hardware, all the positive feedback loops in EFFECTIVE intelligence are present for cultural evolution, and the cycle time shortens and reshortens, Harris writes.

                He says that now about a billion of the world’s nearly 7 billion humans have regular access to the Internet. Another decade or two should see this level of interconnectivity—only 15 years old now—nearly complete.

                When the average person has access to the Internet, all culture will have moved accessibly OUTSIDE our brains, although the ability to process it still may remain within the organic parts of the machine.

                “What’s taking place now is a new leap-after-leap forward in the pace. The next big jump will take place when human brains talk DIRECTLY to computers and to each other.”

                Composite minds more intelligent than any single person are something we’ve already experienced. They impart to our high-tech culture some of its alien-like nature, as though it were controlled by a “godlike conspiracy,” Harris writes.

                The experience of being part of a superintelligence is like being part of a team. To everybody on the team, it feels “as if a godlike people are doing most of the work someplace else,” Harris says. Our experience within our own brains mimics this to a degree, because most of what we do and think goes on BELOW the surface of our conscious awareness. We get some hint of that in our dreams when parts of our brains engaged in modeling the actions of other people split off and take control, acting as bizarre playwrights.

                At some point, it won’t matter much whether computers are smarter than humans, because the Internet of brains and computers that directly link them will reach a capacity to do the next step, which is to control and grow computational matter. Then, organic brains as we know them will no longer be needed. “That shouldn’t be too scary,” Harris writes, “because the ‘people’ who inhabit such collective thinking organizations will still be part of the whole conscious entities. BUT these people WILL BE PROGRAMS, ‘running’ on substrates other than gray matter.”

                The final evolutionary phase will be a pure expression of what we’ve recently been calling “cultural evolution.” Ultimately, the evolution of software, ideas, and knowledge is the only evolution that counts on short time scales. Any software or hardware design innovation can be translated eventually into thinking “hardware,” without waiting for a preset-style “organic” brain to grow in the womb, be born and be programmed. Those quotes around “hardware” (or “wetware”) are needed to remind us that COMPUTRONIUM (the human-made material used to do the information procesing) need not be silicon chips, and almost certainly won’t be. How mechanically “hard” computronium need be is open to question, Harris writes. It may be diamond compiled from carbon atoms, or a diamond sponge. “Certainly the mobile units that connect with it when physical movement is required won’t be metal robots that clatter around.”

                While it isn’t known yet what the mobile units will be made of, “we can imagine that the distinction between living and dead matter will lose its meaning. Any technology capable of copying living organisms is capable of copying them with better and tougher components (diamond-fabric woven bones, for example) and any of this material can justly be called ‘alive,’” Harris says.

                Referring to our bodies in 2009, Harris says that the new “stuff” won’t consist of anything so delicate as 20-micron-size bubbles of water, full of protein and DNA, scaffolded and bound to each other with stringy polymers as though somebody were packing water balloons individually with fishing line and duct tape for long-distance shipping. “That’s an accident,” he writes, “Life started as little balloons that floated around in water and didn’t need much support. When they needed protection they had to develop it by bricolage, and couldn’t redo any of the basics en route. Won’t it be nice to get rid of all of that fragile stuff? The present human body is like a bicycle made of porcelain, which mostly can’t be repaired.”

                “Bodies of the future will not only be much tougher, but will also feature backups of brain information in case of total destruction. In fact, the primary thinking centers probably won’t even be located in the mobile unit/body. There is no reason any of this change need FEEL any different to the user from the body being ‘worn’ now. In fact, it might well feel like an improvement, with enhanced senses and abilities. What feels ‘natural,’ when examined closely, is strange enough already. Remember your present brain sits shock-insulated in the dark, and gets only a view or feel of the world by means of chains of digital signals coming from sense organs. All of this can be manipulated—in theory—at will.”

                The actual structure of computronium is unimportant, Harris writes. Mobile units might be soft and warm and even try for the complete ‘look and feel’ of the human body. On land, one might choose to be an efficiently running four-footed body modified with extra arms and hands. The same applies to exploring other worlds; “if the mobile fits, wear it. Whatever can be designed, will deserve the title and privileges of ‘human being.’ We’ll certainly still think of ourselves as ‘human’—if we remember our heritage.”

                By the time nanotechnology is capable of building complete bodies, using computronium for thinking and other morphable substances for moving, nobody will want to look like a cyborg—except at Halloween, Harris writes. Instead, the body will look and feel however you want it to, sensitive, but tougher than flesh.

                Harris continues: “Of course, since such stuff should be infinitely repairable and connectable [to other brains and the Internet and computers of that future time], it will be effectively immortal. No material is indestructible, but aging as a problem simply goes away once brains are fully inter-connectable because whenever a part (even a  thinking node) is damaged or wears out, consciousness moves to another location until the damaged body or part is replaced.”

Computronium refers to material engineered to maximize its use as a computing substrate. It can refer both to advanced hypothetical materials engineered by nanotechnology on the molecular, atomic, or subatomic level, or to contemporary computing materials.

Currently our computational devices are relatively large, power-hungry, complex individual devices — microchips. This is a problem, because they are not flexible enough, they are expensive to design and manufacture (a new chip fabrication plant costs almost $10 billion).

To move to smaller, cheaper and more flexible design, a transition to parallel processing is needed and the chip manufacturers are already making multi-core CPUs. The next step is to make lots of smaller and smaller chips, the tiniest viable fragments, about a tenth of a millimeter or so, then literally sprinkle them into a viscous medium, and pour out computing material by the pound or by the square inch. In this way you can paint a computer on your wall and if it's not powerful enough you can put on another coat of computer.

Bill Butera from MIT developed a programming model where little code fragments hop from particle to particle, traveling around and self-organizing into a system that solves a problem. The vision is to change the computer from a monolithic box to a raw material that gets configured by instructions traveling through it.

Currently simple chips cost below $1, but they are still traditional chips, meaning the installation is not yet completely trivial. However, they make it possible to gradually add more intelligence to the products (the process that will eventually lead to smart matter).

When the chips become small enough, it will allow a transition from chips to the first real computronium (pourable computing, above), similar to a transition from custom electronics to general-purpose programmable chips in the past. It's important to note, that gaining flexibility doesn't mean a loss in precision. A computronium "liquid" computer can be every bit as precise and reliable (if not more) than a traditional CPU.

Afterwards, the improvement of computronium will be a gradual process, eventually using more and more advanced nanotechnology. The distinction between computing and acting/manufacturing devices will slowly be eliminated and nanorobots will most likely combine both these functions.

Most of the material below was taken from: “Dyson Shell Supercomputers as the Dominant ‘Life Form’ in Galaxies” presented at “Bioastronomy 99: A New Era in Bioastronomy,” in August 1999 by Robert Bradbury of the Aeiveos Corp.:

Most previous discussions of extraterrestrial intelligence have assumed such intelligences bear some similarity to ourselves in our current or near future. These discussions have failed to account for developments that can reasonably be expected in the fields of molecular nanotechnology and biomedical technology in the 21^st century. Intelligent species that decode their genomes should develop the ability to modify their genetic program to extend their lifespan to hundreds of years. The development of full scale molecular nanotechnology enables the uploading of minds into computers with lifespans limited by their hazard function of their local environment in space.

When civilizations have evolved indefinite lifespans there is likely to occur a shift of focus from such activities as simple survival and procreation or the accumulation of wealth to the maximization of intelligence and internal communications bandwidth. These civilizations will also focus on the minimization of their overall hazard function to allow the greatest longevity. Civilizations that are successful in these efforts should become the dominant species in a galaxy.

The fundamental problem facing an advanced technological civilization (ATC) is how to utilize the available matter and energy resources to provide the maximum computational capacity. Current estimates suggest nanotechnology enables mass-doubling times for molecular-scale machinery of an hour. This estimate may be conservative given that bacteria constructed of lower strength materials and generally lacking directed delivery of molecular building blocks can double their mass in 20 minutes. Mass doubling times of this order allow the construction of objects with the mass of the galaxy M31 in nine days.

As scientist Freeman Dyson pointed out, if one has the power of a star available, one can dismantle planets like Jupiter and use it for construction materials. The problem for an ATC then becomes how to obtain such power. The use of self-replicating von Neumann machines allows rapid disassembly of low gravity bodies (e.g. asteroids or small planets). The material from these bodies is hurled into space where it is recast as solar power harvesting devices with an areal mass of about 1 kg/m². These collectors beam power back to the source where it is used to exponentially expand the disassembly process. These methods allow planets such as Mercury to be turned into collectors harvesting the entire solar output in approximately 2 weeks. Further applications of this method would make all of the nonstellar material in solar systems such as ours available for construction within 1,000 years. So in considering the capacities for long-lived ATC we should assume they minimally have the power resources of a star (~10²⁶W) and the matter resources of a solar system (~10²⁶ kg) at their disposal. As such they constitute Kardashev Type II civilizations

A Dyson sphere (or shell as it appeared in the original paper) is a hypothetical megastructure originally described by Freeman Dyson. Such a "sphere" would be a system of orbiting solar power satellites meant to completely encompass a star and capture most or all of its energy output. Dyson speculated that such structures would be the logical consequence of the long-term survival and escalating energy needs of a technological civilization, and proposed that searching for evidence of the existence of such structures might lead to the detection of advanced intelligent extraterrestrial life.

Since then, other variant designs involving building an artificial structure — or a series of structures — to encompass a star have been proposed in exploratory engineering or described in science fiction under the name "Dyson sphere". These later proposals have not been limited to solar power stations — many involve habitation or industrial elements.

While it is believed that some of the design variants commonly described – specifically those based on the Dyson shell – are impractical, if not physically impossible. Design variants of the sphere based on orbiting satellites or solar sails do not require any major theoretical breakthroughs in our basic scientific understanding for their construction. Deployment of spacecraft and satellites using photovoltaics might be seen as the first small steps towards building a Dyson swarm. However, creating and deploying energy-gathering spacecraft and satellites in the numbers needed to create a solar-system-sized integrated energy-gathering system are well beyond our present-day industrial needs or capabilities. It is also likely that there are unforeseen industrial scaling difficulties in such a construction project, and that our current understanding of industrial automation is insufficient to build the self-maintaining systems needed for the sphere's upkeep.

However, there has been some speculation about the creation of ultra light carbon nanotube meshes through molecular manufacturing techniques whose density would be below 0.1 g/m². If production of such materials on an industrial scale is feasible, and such materials could be used in light sails, the average sail density with rigging might be kept to 0.3 g/m² (a "spin stabilized" light sail requires minimal additional mass in rigging). If such a sail could be constructed at this areal density, a space habitat the size of the L5 Society's proposed O'Neill cylinder – 500 km², with room for over 1 million inhabitants, massing 3 × 10⁶ tons – could be supported by a circular light sail 3,000 km in diameter, with a combined sail/habitat mass of 5.4 × 10⁹ kg. For comparison, this is just slightly smaller than the diameter of Jupiter's moon Europa (although the sail is a flat disc, not a sphere), or the distance between San Francisco and Kansas City. Such a structure would, however, have a mass quite a lot less than many asteroids. While the construction of such a massive inhabitable statite would be a gigantic undertaking, and the required material science behind it is as yet uncertain, its technical challenges are slight compared to other engineering feats and required materials proposed in other Dyson sphere variants.

A third type of Dyson sphere is the "Dyson bubble". It would be similar to a Dyson swarm, composed of many independent constructs (usually solar power satellites and space habitats) and likewise could be constructed incrementally.

Unlike the Dyson swarm, the constructs making it up are not in orbit around the star, but would be statites—satellites suspended by use of enormous light sails using radiation pressure to counteract the star's pull of gravity. Such constructs would not be in danger of collision or of eclipsing one another; they would be totally stationary with regard to the star, and independent of one another. As the ratio of radiation pressure and the force of gravity from a star are constant regardless of the distance (provided the statite has an unobstructed line-of-sight to the surface of its star), such statites could also vary their distance from their central star.

The practicality of this approach is questionable with modern material science, but cannot yet be ruled out. A statite deployed around our own sun would have to have an overall density of 0.78 grams per square meter of sail. To illustrate the low mass of the required materials, consider that the total mass of a bubble of such material 1 AU in radius would be about 2.17 × 10²⁰ kg, which is about the same mass as the asteroid Pallas.

Such a material is currently beyond our ability to produce; the lightest carbon-fiber light sail material currently produced has a density – without payload – of 3 g/m², or about four times heavier than would be needed to construct a solar statite.

Megascale and nanoscale engineering currently do not exist.  Megascale engineering results in the progression of trends in the engineering of large scale structures such as pyramids, oil tankers, suspension bridges, tunnels, sky-scrapers and rockets.  Nanoscale engineering results from trend progressions in microelectronic lithographies, micromachining, microvolume and combinatorial chemistry, biotechnology manipulation of genes and proteins, robotics and computer science.

It is paradoxical that many people more easily envision megascale engineering than nanoscale engineering.  The most logical explanation for this is that our senses are able to directly interact with megascale structures, while intermediaries such as atomic force microscopes or enzymes are required to sense and manipulate things at the nanoscale level.  It is important to remember that atomic scale pumps, motors, engines, power generation apparatus and molecular manipulators (enzymes) exist in every individual reading this document.  By mid-1998, the complete genomic DNA sequences (nanoscale programs) for more than 30 different bacteria and yeast (nanoscale assembly and replication machines) were known.  Nanoscale technology exists and is rapidly being domesticated by humans.

As has been pointed out by Dyson [1960, 1968], Kardashev [1985,1988,1997], Berry [1974], and Criswell [1985], the progression of existing population and economic growth, power and mass management trends in our society will enable the construction of Matrioshka Brains using existing (non-nanoscale) technologies within at most a few thousand years. Nanoscale assembly per se is not required.  Current trends in silicon wafer production, if continued, would allow the production of sufficient microprocessors, of current primitive designs, to create a MB by 2250.  It would however require most of the silicon in the planet Venus as raw material. A MB built from such processors would have capabilities significantly less than the limits which would be available using nanoscale fabrication.  Even so, a computing machine built out of even these primitive components would have a thought capacity in excess of a million times the thought capacity of the 6 billion-plus people now populating the planet!  A small fraction of this thought capacity devoted to extending engineering methods should in a brief period develop nanoengineering and assembly to its ultimate limits.

The Kardashev scale is a method of measuring a civilization's level of technological advancement. The scale is only theoretical and in terms of an actual civilization highly speculative; however, it puts energy consumption of an entire civilization in a cosmic perspective. It was first proposed in 1964 by the Soviet Russian astronomer Nikolai Kardashev. The scale has three designated categories called Type I, II, and III. These are based on the amount of usable energy a civilization has at its disposal, and the degree of space colonization. In general terms, a Type I civilization has achieved mastery of the resources of its home planet, Type II of its solar system, and Type III of its galaxy.

Energy is a static quantity and is denoted in joules. Power is a measure of energy transfer over time, and is denoted in watts (joules per second). The three levels of the Kardashev Scale can be quantified in units of power (watts) and plotted on an increasing logarithmic scale.

Type I — a civilization that is able to harness all of the power available on a single planet — has approximately 10¹⁶ or 10¹⁷ W available. Earth specifically has an available power of 1.74  × 10¹⁷ W (174 petawatts, see Earth's energy budget). Kardashev's original definition was 4  × 10¹² W — a "technological level close to the level presently attained on earth" ("presently" meaning 1964).

Type II — a civilization that is able to harness all of the power available from a single star, approximately 4  × 10²⁶ W. Again, this figure is variable; the Sun outputs approximately 3.86  × 10²⁶ W. Kardashev's original definition was also 4  × 10²⁶ W.

Type III — a civilization that is able to harness all of the power available from a single galaxy, approximately 4  × 10³⁷ W. This figure is extremely variable, since galaxies vary widely in size; the stated figure is the approximate power output of the Milky Way. Kardashev's original definition was also 4  × 10³⁷ W.

Using nuclear explosion tests as a perspective, Tsar Bomba, the largest nuclear weapon ever detonated, released an estimated 57 megaton yield; even a Type I civilization makes use of roughly 25 megatons of TNT equivalent a second. A Type II civilization controls 4 × 10⁹ times more energy (4 billion hydrogen bombs per second), and a type III 10¹¹ times more yet.

Current human civilization (2009) has a Kardashev value of about 0.718. However, the Kardashev scale was not developed to model a specific civilization. It's primarily used by SETI researchers, science fiction authors, and futurists as a theoretical framework.

Human civilization is currently somewhere below Type I, as it is able to harness only a portion of the energy that is available on Earth. The current state of human civilization has thus been named Type 0. Although intermediate values were not discussed in Kardashev's original proposal, Carl Sagan argued that they could easily be defined by interpolating and extrapolating the values given above. In 1973, he calculated humanity's civilization type to be 0.7, in relationship to Kardashev's model for Types 0 and I.

As of 2007, the Fractional Kardashev equivalent is approximately 0.72, calculated using BP's primary energy consumption chart for 2007. It is important to note that as Sagan's fractional Kardashev scale is base-10 logarithmic, a value of 0.72 means we are using approximately 0.16% of the total available planetary energy budget.

Methods by which a civilization could feasibly advance to Type I:

Large scale application of fusion power. Type I implies the generation of about 5 kg of energy per second. This can be achieved by fusing about 1,000 kg of hydrogen into helium each second, a rate of about 3 × 10¹⁰ kg/year. A cubic km of water contains about 10¹¹ kg of hydrogen, and the Earth's oceans contain about 1.3 × 10⁹ cubic km of water. So this rate of production can be sustained over geological time scales.

Anti-matter production is still beyond our civilization's ability to utilize as a power source, but any civilization with the technological ability to produce or collect anti-matter in large quantities cheaply, would have a mechanism to produce power on a scale several factors above our current level of technology. In antimatter-matter collisions, the entire rest mass of the particles is converted to kinetic energy. The energy per unit mass is about 10 orders of magnitude greater than chemical energy (compared to TNT), about 4 orders of magnitude greater than the energy that humans liberated today using nuclear fission, and about 2 orders of magnitude greater than the best possible from fusion. The reaction of 1 kg of anti-matter with 1 kg of matter would produce 1.8 × 10¹⁷ J (180 petajoules) of energy (by the mass-energy equivalence formula E = mc²), or roughly the equivalent of 47 megatons of TNT.

Solar energy — converting sunlight into electricity by either solar cells or indirectly through wind and hydroelectric power. Currently, there is no known way for human civilization to successfully utilize the equivalent of the Earth's total absorbed solar energy without completely coating the surface with man-made structures, which is presently not feasible. However, if a civilization constructed very large space-based power satellites, Type I power levels might be achievable.

Type II civilizations might employ:

A Dyson sphere or Dyson swarm and similar constructs are hypothetical megastructures originally described by Freeman Dyson as a system of orbiting solar power satellites meant to completely enclose a star and capture most or all of its energy output.

Type III civilizations might use the same techniques employed by a Type II civilization, but applied to all of the stars of one or more galaxies individually. They may also be able to tap into the energy produced from a supermassive black hole which are believed to exist at the center of most galaxies.

Civilization Implications

There are many historical examples of civilizations undergoing large-scale transitions, such as the Industrial Revolution. The transition between Kardashev scale levels could potentially represent similarly dramatic periods of social upheaval, since they entail surpassing the hard limits of the resources available in a civilization's existing territory. A common speculation suggests that the transition from Type 0 to Type I might carry a strong risk of self-destruction since there would no longer be room for further expansion on the civilization's home planet, similar to a Malthusian catastrophe. Excessive use of energy without adequate disposal of heat, for example, could make the planet of a civilization approaching Type I unsuitable to the biology of the dominant life-forms and their food sources. If Earth is an example, then sea temperatures in excess of 35 °C would jeopardize marine life and make the cooling of mammals to temperatures suitable for their metabolism difficult if not impossible. Of course, these theoretical speculations may not become problems in reality thanks to the application of future engineering and technology.

April 15, 2009

When my cousin Bob and I were both 15, we went to the wedding party of my dad’s littlest brother. Bob was dad’s sister’s second-oldest son. We lived in southwestern Minnesota and they lived north of Minneapolis near Bob Dylan’s home turf. Consequently, I only saw Bob at family reunions—or once or twice a year.

But his round face topped off with a shock of blonde, messy hair and decorated with an unending grin spelled fun and mischief. I loved him.

My uncle’s wedding was the last time I saw my cousin as a whole, healthy person. He and I teased the bartender, trying to sneak a beer. The barkeep wouldn’t give us one. Finally, the combination of my innocence and Bob’s stealth grin forced the man to top off a beer for each of us with strawberry soda.

We had our beer and could drink merrily in front of our parents. Another rite of passage.

Shortly after high school graduation, I heard that Bob had incurable Lou Gehrig’s Disease (amyotrophic lateral schlerosis or ALS). My dad’s sister began flying with him all over the U.S. and to some other countries with money they didn’t have to try exotic or fraudulent cures. This was the early 1970s.

The last time I saw Bob was when I arranged with one of his sisters for her to bring him to a small restaurant on the outskirts of his home town. We were both about 25.

I recognized him only by the sparkle in his eyes. He sat in a wheel chair curled into the shape of a sea horse or a 93-year-old woman with osteoporosis. He was 99 percent paralyzed. The only parts of his body he could move were on his face and a bit of his right arm. I had to shake the one finger he could move instead of his whole hand, or instead of the jovial bear-hug we would have executed as 15 year olds. His sister had to interpret his speech, which came out as mumblings only someone who knew him intimately could decipher.

Amyotrophic lateral sclerosis is a progressive, fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. In the United States and Canada, the condition is often referred to as Lou Gehrig's Disease, after the New York Yankees baseball star who was diagnosed with the disease in 1939 and died from it in 1941, at age 37; today, renowned physicist Stephen Hawking is likely the best-known living ALS patient.

The disorder causes muscle weakness and atrophy throughout the body as both the upper and lower motor neurons degenerate, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, develop twitches because of denervation, and eventually atrophy because of that denervation. The patient may ultimately lose the ability to initiate and control all voluntary movement; bladder and bowel sphincters and the muscles responsible for eye movement are usually (but not always) spared.

Cognitive function is generally spared. The victim is fully aware that he or she is dying, that it will take years, and he or she will suffer and have no control over their lives.

Bob died when we were both about 28. I’m 54 and there still is no cure—and barely any ameliorative measures—for ALS. I believe that one of the main reasons has been the religious taboos against adult stem cell therapy or research. Too many people believe research on adult human stem cells is condemned by God.

Well, this is another confused human rationale that will have to fall. Leonardo DaVinci, revered today, faced similar religious taboos when he first drew the human body in great detail, including the inner organs. However, many of us now are able to live into our 80s and beyond because DaVinci broke those taboos, thus permitting development of many medicines and surgeries we rely on and don’t realize would have been impossible without DaVinci’s courageous act.

Recently, I had the opportunity to ask some questions of Tom Maniatis at Harvard, who is past chair of the national ALS Association’s Research Committee. He is the Thomas H. Lee Professor of Molecular and Cellular Biology and chairman of the Department of Biochemistry and Molecular Biology at Harvard University. Dr. Maniatis will assume the role of the chair of the Department of Biochemistry and Molecular Biophysics of the Columbia University College of Physicians & Surgeons at the beginning of the 2009-2010 academic year.

My questions included:

1) What is the primary research focus w/r ALS now in the U.S.?
Dr. Maniatis: ALS is a complex disease, and is therefore being approached on many different fronts. From my perspective the following are the most exciting and promising:
A. Genetics – two directions:
1. Identification of genes that when mutated cause ALS. This is generally considered the most exciting recent advance for two reasons. First, mutations in two genes have recently been shown to cause ALS, and both genes have been implicated in RNA expression or processing (they both bind RNA). One gene, called TDP-43 is important because it links, for the first time familial and sporadic ALS. The role of TDP43 was first recognized in the analysis of protein aggregates in post-mortem samples of patient spinal cords. Analysis of these cytoplasmic aggregates revealed the presence of TDP43. Subsequently genetic studies revealed the presence of mutations in the TDP43 gene in both familial and sporadic ALS patients. The second gene, called FUS/TLS was discovered more recently, and is also associated with both familial and sporadic ALS. Intense studies of the normal function of these genes are in progress, and efforts are being made to generate mouse models and to study motor neurons derived from patient fibroblasts (induced pluripotent stem cells (iPS – see below).
2. Genetic Linkage studies: Thousands of patient DNA samples have been analysed for genetic linkage to sequence polymorphisms, and a few candidate genes have been identified. However, I think it is fair to say that the field has been disappointed by the lack of clear candidate genes.
B. Stem Cells:
Two directions:
1. Therapy – The most promising avenue is to introduce genes encoding trophic factors into stem cells. The idea here is to introduce genes that encode growth or trophic factors into human embryonic stem cells, differentiate these cells to generate motor neurons, and then introduce them into the spinal cords of ALS patients. The idea is to populate the spinal cord with cells capable of secreting factors that slow motor neuron death. Animal studies have been carried out and efforts are underway to develop this approach for clinical trials. An alternative, and in my opinion, much longer term approach is to actually replace dying motor neurons in ALS patients with functional stem cell-derived motor neurons. The greatest challenge here is to correctly rewire motor neurons so they function normally. This is an enormous challenge that will require significant technical advances, and may simply not work. However, the potential benefit is so great this effort should be supported.
2. Disease Mechanisms: This is the most promising immediate benefit of stem cell research. The idea here is to collect skin cells (fibroblasts) from ALS patients, turn them into so called induced pluriportent stem cells (iPS cells) using well established methods, and then use these cells to generate motor neurons and astroglia for studies in cell culture. In fact, the first two steps have been achieved – that is the generation of patient derived iPS cells and their differentiation in culture to motor neurons. The last step – observation of disease properties has yet to be demonstrated in long term culture. If this does work, this approach will provide an excellent system for studying ALS disease mechanisms in cell culture, and will provide an excellent cell based assay for drug screening. An encouraging note, this approach has worked with mice – that is, it was possible to generate motor neurons from stem cells taken from the SOD1ALS mouse model, and show that they display disease properties in long term culture. We are currently using this approach to study disease mechanisms and test potential drugs. Another benefit of this study was the important discovery that cells other than motor neurons plan an important role in disease progression. Specifically, it was possible to show that astroglia (the cells that surround, contact, nourish and support motor neurons) play an essential role in the disease, at least in the SOD1 mouse model of ALS. In fact, it appears that astroglia derived from the SOD1 mouse stem cells secrete toxic factors that kill motor neurons. Efforts are underway to identify these toxic factors.

2) How does stem-cell research rank in importance? And what kind of stem cell research are we talking about?
Dr. Maniatis: Answered above – I consider stem-cell research to be of great importance, both in the development of treatments for ALS and for understanding disease mechanisms.

a) If it's not the ultimate path to a cure, what could be?
Dr. Maniatis: Too early to answer – best hope is to identify small molecule drugs that prevent neurodegeneration – the best current assay system is stem cell-derived motor neurons and glia.

b) How do religious or cultural taboos affect research in the U.S. and around the world?
Dr. Maniatis: The implications in the U.S. are obvious. The restrictions on stem cell research have severely hampered progress. Although iPS cell technology may be successful, the use of these cells for therapy is not possible without further advances. No progress has been made with alternative approaches such as nuclear transfer because of the restrictions. Even though more human embryonic stem lines can be used for NIH-supported research, the development of new lines will be difficult considering the guidelines.

c) Is there a cost or cost per year estimate of both current research and current attempts with today's drugs?
Dr. Maniatis: I am not in a position to answer this question – it depends on the focus of NIH and private foundations.

3) What do you and ALS think of adult stem cell therapy? Will it be the ultimate path?
Dr. Maniatis: I think it is way to early to predict the ultimate path – all directions (adult and embryonic stem cells) should be aggressively pursued.

a) Q Therapeutics has a product called "Q-cells" used in "autologous" stem cell therapy. They claim significant success. Is this true? If not, why?
Dr. Maniatis: I think the idea is sound – that is to provide myelin and trophic support to dying neurons, but it is currently much too early to get excited. The results in animal models have been positive but modest, and much more work will have to be done before they can be tested in the clinic. Basically, I think this is a positive direction, but we have a long way to go, and to make value judgements on which approach is better or worse is premature.

.

Nov. 5, 2009
 
“Science without religion is lame, religion without science is blind.”
--Albert Einstein, German born American physicist who developed the special and general theories of relativity. Nobel Prize for Physics in 1921. (1879-1955)

One stranger in France bought me dinner, one former coworker here in New York City asked me out on a date. I was repulsed both times. Nothing could have gotten me to kiss those guys unless, perhaps, Sean Penn’s paycheck for his role in “Milk.” I know that my wife would be repulsed by offers made by women, as would have my mother.
As I told the leader of our Mormon church in our area of Manhattan, “If you’re repulsed by the same sex, nothing is going to change that. By the same token, if you feel attracted to the same sex, nothing is going to change that, and the Mormon Church’s attempts to restrict gays from important roles within that church is only going to make those gays who choose to remain, repressed and angry, even though they may hide it so that they’ll gain glory after death, of course.”
If we are to keep in mind what Einstein said, they we must look at what science says, and science says that you cannot change someone from gay to straight, nor is that person’s orientation an act of free will, as the Mormon church and so many other blind churches would have it:
The American Psychological Association, American Psychiatric Association, and National Association of Social Workers stated in an amicus brief presented to the Supreme Court of the State of California: "Sexual orientation has proved to be generally impervious to interventions intended to change it, which are sometimes referred to as “reparative therapy.” No scientifically adequate research has shown that such interventions are effective or safe. Moreover, because homosexuality is a normal variant of human sexuality, national mental health organizations do not encourage individuals to try to change their sexual orientation from homosexual to heterosexual. Therefore, all major national mental health organizations have adopted policy statements cautioning the profession and the public about treatments that purport to change sexual orientation."^[3] The Royal College of Psychiatrists stated that it "shares the concern of both the American Psychiatric Association and the American Psychological Association that positions espoused by bodies like the National Association for Research and Therapy of Homosexuality (NARTH) in the United States are not supported by science. There is no sound scientific evidence that sexual orientation can be changed. Furthermore so-called treatments of homosexuality as recommended by NARTH create a setting in which prejudice and discrimination can flourish,"^[23] and added that "The best evidence for efficacy of any treatment comes from randomised clinical trials and no such trial has been carried out in this field."^[24]
The APA also writes that "most people experience little or no sense of choice about their sexual orientation".^[25] In a joint statement with other major American medical organizations, the APA says that "different people realize at different points in their lives that they are heterosexual, gay, lesbian, or bisexual".^[26]
There is no consensus among scientists about the exact reasons that an individual develops a heterosexual, bisexual, gay, or lesbian orientation.^[75] The main reasons cited include genetic and environmental factors, likely in combination.^[76][77] Other factors that may play a role include prenatal hormone exposure, where hormones play a role in determining sexual orientation as they do with sex differentiation;^[78][79] and prenatal stress on the mother.
Yet, gays in recent weeks have experienced setbacks brought on by the less-educated, masses who fear something that grosses them out. I admit that the sight of two men kissing in New York’s parks and the thought of them having sex repulses me, I have to accord them equal rights. When they talk about their upcoming date with another man with the nervousness that I would talking about a date when I was younger, it weirds me out. But, as religious organizations never cease to point out, we have to do god’s will. My version of that is that, as the psychological organizations indicate, homosexuality is normal, and not an immoral choice of free will. So I have to accept them. They have equal rights with all creatures called homo sapiens sapiens.
Voters in Maine on Nov. 3 repealed the state's same sex marriage law after an emotionally charged campaign that drew large numbers to the polls and focused national attention on Maine.
"Question 1 has passed," Frank Schubert, campaign manager of Stand for Marriage Maine, announced in Portland. "It has all come together tonight and the institution of marriage has been preserved."
"We went up against tremendous odds," Marc Mutty, public affairs director for the Roman Catholic Diocese of Portland who has been on loan to the campaign, said from Portland. "We all know we were the little guy going up against the big guy, but we prevailed. We prevailed because the people of Maine - the silent majority - the folks back home spoke with their votes.
"What they had to say," Mutty continued, "is marriage matters because it's between a man and a woman. [This campaign] has never been about hating gays, but about preserving marriage and only about preserving marriage, and that's what we did tonight."
But while gay marriage supporters hoped the high voter interest would provide a boost, it was not enough to make Maine the first state in the nation where gay marriage won at the polls rather than in the legislature or courts.
Despite the outcome, Mary Bonauto, a No on 1 executive board member and attorney with Gay and Lesbian Advocates and Defenders, said she was never more proud to live in Maine and raise a family with her long-term partner. She was especially proud of the attention the No on 1 campaign brought to the values shared by all families, regardless of sexual orientation.
"I look around at the 8,000 volunteers, and the vast majority are not gay people," Bonauto said. "So that gives me hope that, regardless of the outcome, that this discussion has changed the state."
With relatively few high-profile elections around the country, the national media spotlight is on Maine. Had Question 1 been defeated, Maine would have become the first state in the nation where same-sex marriage was legalized at the ballot box.
Although the campaign is over, the Rev. Bob Emrich of Palmyra said that the work of traditional marriage supporters was not.
"God has given us this victory," Emrich continued, "and it is very important for us to recognize that he is the one who put the energy into this campaign. So let's not be so arrogant to forget this. It's very appropriate to pause for a moment of prayer."
Just a few days before, on Oct. 31, came the news that Pope Benedict XVI had invited members of the Anglican Communion to abandon their church and join his. His invitation was addressed to Anglicans who are uncomfortable with gays and women as clergy.
It was a generous invitation and it was extended just 10 days before Halloween which is of no particular significance since that is only one day before All Saints day, a day that, unlike the Pope's invitation, has nothing to do with spookiness.  The invitation was a blanket invitation to Episcopalians, as they are known in the U.S., to abandon the Episcopal ship and set sail with one captained by the Pope. 
In an October 20^th press conference at the Vatican, Cardinal William Levada, prefect of the Congregation for the Doctrine of the Faith, said that something called an "Apostolic Constitution" had been created that would enable Anglican faithful and their clergy to enter "into full communion with the Church."  He described it as a "single canonical model for the universal Church which is adaptable to various local situations and equitable to former Anglicans in its universal application." He explained that the Pope hopes that the new enrollees can "preserve those Anglican traditions precious to them and consistent with the Catholic faith.  Insofar as these traditions express in a distinctive way the faith that is held in common, they are a gift to be shared in the wider Church." (The gift to which he was referring includes neither women nor gays.)
It is gratifying that those who have deep-rooted opposition to gays and women in the priesthood have been welcomed to the company of the faithful who believe as they do and do so in the name of the Lord.   The invitation is proof to the recipients that what was perceived as bigotry by those from whom they parted, is not bigotry at all but good sound theology.  Inviting the congregants to join is not, however, the most amazing thing about the Church's new openness. 
For many centuries celibacy has been the watchword for those entering the Church's priesthood.  The reasons for it are diverse and it has in many cases been more honored in the breach than in the observance as shown by the hundreds of millions of dollars paid out by the Church in settlement of claims involving priestly pedophilia.  Notwithstanding those episodes and tales of priests who secretly father children, the Church remains adamant that priests should live a life of celibacy.  It is also aware, however, of the economic hardship that will be imposed on a married Anglican priest whose congregation moves whole cloth over to what was formerly the opposition, if he cannot join in the exodus.  Accordingly, the new plan permits Anglican priests who are married to be ordained as Roman Catholic priests.  They will not, however be eligible for promotion to Bishop or higher ecclesiastical office such as Cardinal or Pope, a minor drawback since few priests attain those posts.
[It is amazing how the rules can be twisted in the name of a god who is said to speak only to the stewards—priests and bishops—of two major churches to fit the preferences of largely, older, white males.]
The newfound openness shown by accepting disaffected Episcopalians into the Roman fold may be just the first step.  If the Pope wants to make a home for other people who don't much care for gays and believe that women should be treated differently from men, he may want to reach out to the Taliban.  Their attitudes are not as dissimilar as one might hope, said Christopher Brauchli at http://humanraceandothersports.com

March 20, 2010

Summary: Karel Svoboda's lab is searching for the substrates of experience-dependent plasticity in the developing and adult neocortex. The functional properties of the brain must change in response to salient sensory experiences, but the nature of these changes at the level of synapses, neurons, and their networks (also known as the engram) is unknown.

Most of the cognitive functions in mammals, ranging from perception to memory formation, are performed in the neocortex, a massive network of neurons. Neurons are linked into circuits by synapses, which pass information between neurons. How do the circuits and synaptic mechanisms underlying this awesome neural network produce our perception of the world? How “plastic” are these neural circuits, that is, how do the physical properties of the neural network change in response to experience? The answers to these questions will profoundly change our understanding of the function and diseases of the brain.

Cortical tissue is dauntingly complex. Each module of cortical tissue (~1 mm³ of gray matter) contains nearly a million neurons, each of which connects to thousands of other neurons. To observe neurons and synapses in the intact brain, we build and use sensitive tools. Two-photon laser scanning microscopy (2PLSM) allows us to image single synapses in intact tissues and to track changes in intracellular calcium and signal transduction events. Excitation of neuronal elements by focal uncaging of neurotransmitters allows us to probe the structure of cortical circuits efficiently. We combine these optical methods with electrophysiological measurements of synaptic currents and potentials and molecular manipulations of neurons.

Cortical Circuits and Their Plasticity
The neocortex consists of about a dozen types of neurons. How are these neurons wired into circuits? The wiring diagram of the brain is fundamental to understanding cortical function and plasticity. However, little quantitative information about circuitry is available. What are the sources of input to a neuronal subtype and what are their relative strengths? Which synaptic pathways change with novel sensory experience?

We are using laser scanning photostimulation (LSPS) to measure the structure of cortical circuits. LSPS allows us to rapidly map the spatial distributions of synaptic input to individual neurons. We have applied LSPS to the rodent barrel cortex. Similar to other sensory areas in the mammalian cortex, the barrel cortex is arranged in maps. Each whisker is represented by a small cortical region (barrel). Whisker maps are shaped by experience during development and reshaped in the adult.

The Janelia Farm Research Campus is a research campus of the Howard Hughes Medical Institute that opened in October 2006. The campus is located in Loudoun County, Virginia, near the town of Ashburn. It is known for its scientific research and modern architecture.

We have discovered that the barrel cortex contains interdigitated columnar circuits—barrel and septal columns—that process input from distinct thalamic nuclei. In developmental studies we found that cortical columns develop with remarkable specificity, without detectable "overgrowth" and "pruning." By comparing circuits in normal and deprived animals, we performed an unbiased search for the synaptic pathways that undergo experience-dependent plasticity during development. We found that the strengths of excitatory layer 4 → layer 2/3 connections changed with opposing signs in barrel and septal columns. These measurements provide an explanation of previous in vivo measurements of plasticity at the level of synaptic pathways. We applied LSPS to analyze the development and plasticity of barrel cortex circuits in mice lacking the FMR protein, an animal model for fragile X mental retardation, and detected highly specific developmental defects in particular synaptic pathways.

Experience-Dependent Structural Synaptic Plasticity
Understanding plasticity at the level of circuits is just one piece of the puzzle. What changes at the level of neurons and synapses in particular synaptic pathways in response to novel sensory experience? Answers to this question are fundamental to the mechanisms of plasticity and the memory capacity of the brain. Our approach has been to image synapses in transgenic mice in vivo over long times as plasticity happens.

We find that the large-scale arborization of axons and dendrites is stable, but that neurons display a rich repertoire of micrometer-level structural plasticity of dendritic spines, axonal terminals, and axonal branch tips. A subpopulation of dendritic spines appear and disappear. Retrospective electron microscopy has revealed that spine growth and retraction are associated with synapse formation and elimination, respectively, and underlie aspects of experience-dependent changes in circuits.

We have recently turned our attention to synapse stability. Many synapses persist for months, perhaps the entire life of the animal, and also maintain their size. This is remarkable because synapses are tiny structures composed of just a handful of proteins of a given type. Protein lifetimes are on the order of days. To study the underpinnings of synapse stability, we have developed methods to measure the trafficking of synaptic proteins at the level of individual synapses in vivo. Remarkably, we find that the major scaffolding protein PSD-95 unbinds from synapses over tens of minutes and exchanges with proteins in neighboring synapses. Larger synapses scavenge diffusing PSD-95 more efficiently and also hold on to PSD-95 longer. The interactions between synapses and their proteins are thus tuned to maintain the synaptic status quo against dissipation by diffusion.

The Function and Plasticity of Single Synapses
Cortical plasticity and memory are thought to manifest themselves physiologically at synapses. A cortical synapse consists of a presynaptic terminal and a postsynaptic spine, tiny compartments (~0.1 μm³) that contain only a few signal-transducing molecules, such as channels and receptors. To understand signal and noise in synaptic transmission, it is therefore necessary to study single synaptic contacts. We have developed methods based on calcium imaging to detect the activation of N-methyl-D-aspartate receptors (NMDA-Rs) in individual spines in response to the release of single quanta of neurotransmitter. We measured the fractional activation of synaptic receptors after neurotransmitter release and found that synaptic receptors are far from saturation. In fact, often only a single receptor opened in response to neurotransmitter release. Synapses are therefore noisy, but capable of linearly transmitting presynaptic release. We have also dissected the mechanisms of calcium influx and handling to gain an understanding of the life cycle of calcium ions in dendrites and spines.

Can we learn about calcium-dependent signaling pathways in spines? One approach uses FRET (fluorescence resonance energy transfer) to image protein-protein interactions, but such measurements are difficult in intact tissue, particularly in microcompartments. To overcome these problems, we have built a sensitive microscope that combines two-photon excitation with fluorescence lifetime imaging microscopy (2pFLIM). We have used 2pFLIM to dissect the role of the small GTPase Ras in synaptic plasticity at the level of single synapses.

Genetics of Neural Circuits
To decipher complex computations and behaviors at the level of cortical circuits we will need to be able to activate and inactivate specific populations of neurons rapidly and reversibly in vivo. To address the problems of inactivation, we have developed MIST (molecules for the inducible inactivation of synaptic transmission). We set out to harness the molecular machinery underlying neurotransmitter secretion to interfere with synaptic transmission, triggered by administration of small-molecule drugs. We use drugs that induce dimerization of small protein domains. These domains were attached to a variety of proteins important in the synaptic vesicle cycle. Candidate systems were transfected into cultured neurons and screened for potent, inducible, and reversible inactivation of the synaptic vesicle cycle. We developed two distinct MISTs, based on the synaptic vesicle proteins synaptophysin and VAMP (vesicle-associated membrane protein). These systems have been tested in vitro and in vivo. For example, we have used the L7 promoter to introduce the VAMP-based system into Purkinje neurons. In L7-MIST mice, injection of dimerizer abolishes learning of the rotarod task. We are introducing MISTs into specific subsets of cortical neurons, including thalamus-projecting L6 cells, various subtypes of GABAergic interneurons, and subregions of the hippocampus and neocortex.

For many years, the main way HHMI conducted research was through supporting investigators who worked at their home institution. This is still the majority of HHMI research, with (as of 2009) more than 350 investigators at more than 70 institutions. However, there are interdisciplinary problems that are difficult to address in existing research settings, and Janelia Farm was built to address one of these problems, neurobiology. The campus focuses on interdisciplinary research in this area, specifically addressing:

The identification of general principles that govern how information is processed by neuronal circuits.

The development of imaging technologies and computational methods for image analysis.

In addition to and in cooperation with the individual investigators, there are three large scale interdisciplinary projects at Janelia:^[2]

High-throughput characterizing of the behavioral phenotypes on genetically defined small neural lesions in Drosophila.

Two projects aimed at developing both large-scale neuroanatomical data for Drosophila (at the light and electron microscopy levels) as well as accelerating the technology so that even larger anatomical projects can be approached in the future.

Janelia farm was designed to emulate the unconstrained and collaborative environments at AT&T Bell Laboratories and Cambridge's Laboratory of Molecular Biology. Researchers are on six-year contracts and fully internally funded, independent of traditional research grant funding.

Gerald M. Rubin is the first director of Janelia Farm, and saw it from concept through construction to operation.

Conferences and public lectures

Janelia Farm hosts a series of specialist conferences each spring and fall.^[3] These are normally on topics related to its primary research mission, neurobiology, although there are some conferences on more general topics such as science education.^[4] Janelia also hosts a series of public lectures, for a non-specialist audience, called "Dialogues of Discovery".^[5]

Campus

The 689 acres (2.79 km²) campus features a 900-foot (270 m) long, arc-shaped laboratory known as the Landscape Building. Designed by Rafael Viñoly, the building, 270 feet (82 m) deep at the ground floor, is built into a hill and designed to be the primary research facility.^[6] Landscape enhancements to the larger campus were designed by Lewis Scully Gionet, Inc., and were completed in fall 2008 (and won an Honor Award from the Maryland and Potomac chapters of the American Society of Landscape Architects). This work includes hardscape elements (an architectural water feature, expanded path network, and siting of multiple pieces of artwork, among others) and comprehensive planting additions, and was constructed by Ruppert Nurseries.