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My proposal for the Society for Risk Analysis’s annual meeting in Boston has been accepted, in oral presentation format, for the afternoon of Wednesday, December 10th, 2008. Any Lifeboat members who will be in the area at the time are more than welcome to attend. Any suggestions for content would also be greatly appreciated; speaking time is limited to 15 minutes, with 5 minutes for questions. The abstract for the paper is as follows:

Global Risk: A Quantitative Analysis

The scope and possible impact of global, long-term risks presents a unique challenge to humankind. The analysis and mitigation of such risks is extremely important, as such risks have the potential to affect billions of people worldwide; however, little systematic analysis has been done to determine the best strategies for overall mitigation. Direct, case-by-case analysis can be combined with standard probability theory, particularly Laplace’s rule of succession, to calculate the probability of any given risk, the scope of the risk, and the effectiveness of potential mitigation efforts. This methodology can be applied both to well-known risks, such as global warming, nuclear war, and bio-terrorism, and lesser-known or unknown risks. Although well-known risks are shown to be a significant threat, analysis strongly suggests that avoiding the risks of technologies which have not yet been developed may pose an even greater challenge. Eventually, some type of further quantitative analysis will be necessary for effective apportionment of government resources, as traditional indicators of risk level- such as press coverage and human intuition- can be shown to be inaccurate, often by many orders of magnitude.

More details are available online at the Society for Risk Analysis’s website. James Blodgett will be presenting on the precautionary principle two days earlier (Monday, Dec. 8th).

Researchers have devised a rapid and efficient method for generating protein sentinels of the immune system, called monoclonal antibodies, which mark and neutralize foreign invaders.

For both ethical and practical reasons, monoclonals are usually made in mice. And that’s a problem, because the human immune system recognizes the mouse proteins as foreign and sometimes attacks them instead. The result can be an allergic reaction, and sometimes even death.

To get around that problem, researchers now “humanize” the antibodies, replacing some or all of mouse-derived pieces with human ones.

Wilson and Ahmed were interested in the immune response to vaccination. Conventional wisdom held that the B-cell response would be dominated by “memory” B cells. But as the study authors monitored individuals vaccinated against influenza, they found that a different population of B cells peaked about one week after vaccination, and then disappeared, before the memory cells kicked in. This population of cells, called antibody-secreting plasma cells (ASCs), is highly enriched for cells that target the vaccine, with vaccine-specific cells accounting for nearly 70 percent of all ASCs.

“That’s the trick,” said Wilson. “So instead of one cell in 1,000 binding to the vaccines, now it is seven in 10 cells.”

All of a sudden, the researchers had access to a highly enriched pool of antibody-secreting cells, something that is relatively easy to produce in mice, but hard to come by for human B cells.

To ramp up the production and cloning of these antibodies, the researchers added a second twist. Mouse monoclonal antibodies are traditionally produced in the lab from hybridomas, which are cell lines made by fusing the antibody-producing cell with a cancer cell. But human cells don’t respond well to this treatment. So Wilson and his colleagues isolated the ASC antibody genes and transferred them into an “immortalized” cell line. The result was the generation of more than 100 different monoclonals in less than a year, with each taking just a few weeks to produce.

In the event of an emerging flu pandemic, for instance, this approach could lead to faster production of human monoclonals to both diagnose and protect against the disease.

Journal Nature article: Rapid cloning of high-affinity human monoclonal antibodies against influenza virus

Nature 453, 667–671 (29 May 2008) | doi:10.1038/nature06890; Received 16 October 2007; Accepted 4 March 2008; Published online 30 April 2008

Pre-existing neutralizing antibody provides the first line of defence against pathogens in general. For influenza virus, annual vaccinations are given to maintain protective levels of antibody against the currently circulating strains. Here we report that after booster vaccination there was a rapid and robust influenza-specific IgG+ antibody-secreting plasma cell (ASC) response that peaked at approximately day 7 and accounted for up to 6% of peripheral blood B cells. These ASCs could be distinguished from influenza-specific IgG+ memory B cells that peaked 14–21 days after vaccination and averaged 1% of all B cells. Importantly, as much as 80% of ASCs purified at the peak of the response were influenza specific. This ASC response was characterized by a highly restricted B-cell receptor (BCR) repertoire that in some donors was dominated by only a few B-cell clones. This pauci-clonal response, however, showed extensive intraclonal diversification from accumulated somatic mutations. We used the immunoglobulin variable regions isolated from sorted single ASCs to produce over 50 human monoclonal antibodies (mAbs) that bound to the three influenza vaccine strains with high affinity. This strategy demonstrates that we can generate multiple high-affinity mAbs from humans within a month after vaccination. The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared with the virus strain present in the vaccine1. However, we found that most of the influenza-virus-specific mAbs showed the highest affinity for the current vaccine strain. Thus, OAS does not seem to be a common occurrence in normal, healthy adults receiving influenza vaccination.

Researchers from Imperial College in London, England, isolated the receptor in the lungs that triggers the immune overreaction to flu.

With the receptor identified, a therapy can be developed that will bind to the receptor, preventing the deadly immune response. Also, by targeting a receptor in humans rather than a particular strain of flu, therapies developed to exploit this discovery would work regardless of the rapid mutations that beguile flu vaccine producers every year.

The flu kills 250,000 to 500,000 people in an average year with epidemics reaching 1 to 2 million deaths (other than the spanish flu which was more severe

This discovery could lead to treatments which turn off the inflammation in the lungs caused by influenza and other infections, according to a study published today in the journal Nature Immunology. The virus is often cleared from the body by the time symptoms appear and yet symptoms can last for many days, because the immune system continues to fight the damaged lung. The immune system is essential for clearing the virus, but it can damage the body when it overreacts if it is not quickly contained.

The immune overreaction accounts for the high percentage of young, healthy people who died in the vicious 1918 flu pandemic. While the flu usually kills the very young or the sickly and old, the pandemic flu provoked healthy people’s stronger immune systems to react even more profoundly than usual, exacerbating the symptoms and ultimately causing between 50 and 100 million deaths world wide. These figures from the past make the new discovery that much more important, as new therapies based on this research could prevent a future H5N1 bird flu pandemic from turning into a repeat of the 1918 Spanish flu.

In the new study, the researchers gave mice infected with influenza a mimic of CD200, or an antibody to stimulate CD200R, to see if these would enable CD200R to bring the immune system under control and reduce inflammation.

The mice that received treatment had less weight loss than control mice and less inflammation in their airways and lung tissue. The influenza virus was still cleared from the lungs within seven days and so this strategy did not appear to affect the immune system’s ability to fight the virus itself.

The researchers hope that in the event of a flu pandemic, such as a pandemic of H5N1 avian flu that had mutated to be transmissible between humans, the new treatment would add to the current arsenal of anti-viral medications and vaccines. One key advantage of this type of therapy is that it would be effective even if the flu virus mutated, because it targets the body’s overreaction to the virus rather than the virus itself.

In addition to the possible applications for treating influenza, the researchers also hope their findings could lead to new treatments for other conditions where excessive immunity can be a problem, including other infectious diseases, autoimmune diseases and allergy.

On April 16, 2008, NASA News Release 08–103 reaffirmed that its estimation of a 1 in 45,000 chance of impact in 2036 remains valid.

The B612 Foundation is working towardcs the goal of of significantly altering the orbit of an asteroid in a controlled manner by 2015.

the B612 Foundation made estimates of Apophis path if a 2036 Earth impact were to occur.

The impact result is a narrow corridor called the ‘risk corrider’ which would be a few miles wide. Countries estimated to be in the direct path:

- southern Russia,
- across the north Pacific Ocean (relatively close to the coastlines of the California and Mexico), then
- right between Nicaragua and Costa Rica,
- crossing northern Colombia and
- Venezuela and over the Caribbean islands of Trinidad and Tobago,
- over the Atlantic Ocean to the west coast of Africa.


Earth’s Path of Risk for the 99942 Apophis Asteroid that is suspected to be on track for a collision course with earth in the year 2036. This image is self-made from data estimated by the B612 Foundation, this is why it is just an approximation. Credit: Mario Roberto Duran Ortiz Mariordo and the re-use of this image is based on ‘Fair use’ of public domain info by the B612 Foundation work on Apophis.

The hypothetical impact of Apophis along the path of risk could have more than 10 million casualties, however the threatened zones would be evacuated [as per B612 foundation comment. The threat of casualties would be for a similar sized object, if it was not detected.].

Spaceworks Engineering had an award winning plan to send a spacecraft to shadow the Apophis asteroid

A video Foresight: A Radio Beacon Mission to Asteroid Apophis is on Youtube.

The Foresight final report is here

As of October 19, 2006 [and also April 16, 2008′, the impact probability for April 13, 2036, was calculated as 1 in 45,000. An additional impact date in 2037 was also identified; the impact probability for that encounter was calculated as 1 in 12.3 million.

What is metabolomics?

Genes are similar to the plans for a house; they show what it looks like, but not what people are getting up to inside. One way of getting a snapshot of their lives would be to rummage through their rubbish, and that is pretty much what metabolomics does. […]

Metabolomics studies metabolites, the by-products of the hundreds of thousands of chemical reactions that continuously go on in every cell of the human body. Because blood and urine are packed with these compounds, it should be possible to detect and analyse them. If, say, a tumour was growing somewhere then, long before any existing methods can detect it, the combination of metabolites from the dividing cancer cells will produce a new pattern, different from that seen in healthy tissue. Such metabolic changes could be picked up by computer programs, adapted from those credit-card companies use to detect crime by spotting sudden and unusual spending patterns amid millions of ordinary transactions.

This could be used for traditional medicine, both to prevent pathologies and to detect those that are already present so they can be treated. But another use would be as part of an early-detection system to defend against pandemics and biological attacks. As mentioned previously, network-theory can help us better use vaccines. But once you have a cure or antidote, you also need to identify people that are already infected but haven’t died yet, and the earlier you can do that after the infection, the more chances they have to live.

Once the techniques of metabolomics are sufficiently advanced and inexpensive to use, they might provide better data than simply relying on reported symptoms (might be too late by then), and might scale better than traditional detection methods (not sure yet — something else might make more economic sense). It’s a bit too early to tell, but it’s a very promising field.

For more information, see Douglas Kell’s site or Wikipedia: Metabolomics.

Source: The Economist. See also Lifeboat’s BioShield program.

If a pandemic strikes and hundreds of millions are at risk, we won’t have enough vaccines for everybody, at least not within the time window where vaccines would help. But a new strategy could help use the vaccines we have more effectively:

Researchers are now proposing a new strategy for targeting shots that could, at least in theory, stop a pandemic from spreading along the network of social interactions. Vaccinating selected people is essentially equivalent to cutting out nodes of the social network. As far as the pandemic is concerned, it’s as if those people no longer exist. The team’s idea is to single out people so that immunizing them breaks up the network into smaller parts of roughly equal sizes. Computer simulations show that this strategy could block a pandemic using 5 to 50 percent fewer doses than existing strategies, the researchers write in an upcoming Physical Review Letters.

vaccine-targeting.jpg

So you break up the general social network into sub-networks, and then you target the most important nodes of these sub-networks and so on until you run out of vaccines. The challenge will be to get good information about social networks, something not quite as easy as mapping computer networks, but there is progress on that front.

In one of the most dramatic illustrations of their technique, the researchers simulated the spread of a pandemic using data from a Swedish study of social connections, in which more than 310,000 people are represented and connected based on whether they live in the same household or they work in the same place. With the new method, the epidemic spread to about 4 percent of the population, compared to nearly 40 percent for more standard strategies, the team reports.

Source: ScienceNews. See also Lifeboat’s BioShield program.

There is a strong overlap between those concerned about extinction risk prevention and healthy life extension. Accordingly, many supporters of the Lifeboat Foundation will be attending an open event on regenerative medicine taking place on the UCLA campus on the 27th of June. Here is the blurb:

On Friday, June 27th, leading scientists and thinkers in stem cell research and regenerative medicine will gather in Los Angeles at UCLA for Aging 2008 to explain how their work can combat human aging, and the sociological implications of developing rejuvenation therapies. Aging 2008 is free, with advance registration required.

UCLA Royce Hall
Friday June 27th | Doors open 4pm
405 Hilgard Ave, Los Angeles, CA 90024

This special public event is being organized by the Methuselah Foundation. Dr. Aubrey de Grey, chairman and chief science officer of the Methuselah Foundation, said, “Our organization has raised over $10 million to crack open the logjams in longevity science. With the two-armed strategy of direct investments into key research projects, and a competitive prize to spur on competing scientists’ race to break rejuvenation and longevity records in lab mice, the Foundation is actively accelerating the drive toward a future free of age-related degeneration.” The Methuselah Foundation has been covered by “60 Minutes,” Popular Science, the Wall Street Journal, and other top-flight media outlets.

If any Lifeboat Foundation supporters are interesting in meeting up before or after the event, comment on this post.

The report, “Synthetic Biology: Social and Ethical Challenges”, highlights concerns about ownership, misuse, unintended consequences, and accidental release of synthetic organisms into the environment.

Andrew Balmer and Professor Paul Martin, the report’s authors, suggest a threat from “garage biology”, with people experimenting at home. They also emphasise that there is no policy on the impact of synthetic biology on international bioweapons conventions.

Read the entire report here (PDF).

Supercomputer

We are currently hosting lifeboat.com on free web space provided by rubyredlabs.com. Due to the growth in our traffic plus more general activity on this server, it would be best if we had our own server.

Note that we have additional space from KurzweilAI.net on a shared server (shared with many domains) but the shared server is always rather loaded since it has so many domains on it so we don’t host our main pages on it. (We use the shared server for backups, file transfers, and less important domains.)

Our current solution is to stay with the same provider as rubyredlabs.com but to move to our own machine. (This should simplify the transition.) The current provider is theplanet.com. We plan on getting: Intel Xeon 3210 Quad Core Kentsfield Processor, 250GB HDD, 4GB RAM, 2500GB bandwidth, 10 IPs, 100mbps uplink — $199 monthly / $25 setup.

We welcome any feedback. We are currently on a system equal to: Celeron 2.0, 80GB HDD, 1GB RAM, 750GB bandwidth, 5 IPs, 10mbps uplink — $89 monthly / $0 setup but don’t have access to all the systems resources. We just finished completing an upgrade so both our blog pages and regular web pages are cached, enabling us to handle a lot of traffic but it doesn’t help much if the server has activity on it besides ours which is not cached… We also upgraded our spam filter so it runs about one thousand times as fast which was rather helpful.

Our traffic is around 150GB but obviously if it surged a lot it is easier to pay for more bandwidth than to get a new machine on the spot. Also our current machine is running FreeBSD — we plan on getting Red Hat 5 since we have a choice.

We welcome your input on this!

UPDATE: Jaan Tallinn, cofounder of Skype, the only major IM client that both securely authenticates conversation. participants, and encrypts the communication, gets us started with a $300 donation. Our goal is to raise $2,500 to pay for a faster machine for a year.

UPDATE II: Chris Haley agrees to become System Administrator for our new machine. He also donates $1,500 bringing our Bigger Machine Fund to $1,925. Only $575 to go!

SUCCESS! We were able to quickly raise $3,400 for our Bigger Machine Fund — far exceeding our goal of $2,500. Additional funds raised will be used to pay for additional months, for improved network/software/hardware security, and for a backup plan. Long-term, we plan on hosting our site with more than one provider for the ultimate in backup plans. The more you donate, the more infrastructure we will implement.

Crossposted from the blog of Starship Reckless

Note: Like anyone who’s breathing, I have been tracking the Phoenix Lander. So I thought this might be a good moment to share a personal memory of one of its ancestors. That one did not survive to fulfill its mission, but the dream stayed alive. What I said then is even more true today, almost a decade later. The Greek version of this article was published in the largest Greek daily, Eleftherotypia (Free Press).

Prometheus

Prometheus Stealing Fire by André Durand (cropped)

It’s slightly cloudy — unusual for sunny Florida. The ocean-scented air is alive with birds: gulls, pelicans, hawks. On a wooden platform, a group of people of all ages and colors is squinting fixedly at a point on the horizon about two kilometers away, where a gantry holds a slim rocket that balances a tiny load on its nose. A level voice announces from the loudspeakers: “The T minus ten holding period is over. We’re going forward.”

The people break into wild cheers, then fall eerily silent. Curious children are shushed and told to look there, there; final adjustments are made to cameras and binoculars. The minus ten holding period is the last chance to abort. The weather was such that until this moment the decision to launch could change.

Like heartbeats, the announcements come. “T minus five… minus three… minus one… T minus thirty seconds… minus twenty seconds… minus ten seconds… Now you can hear a pin drop. “Nine… eight.. seven… six… five… four.… three… two…” All the spectators shiver, holding their breath.

“Liftoff!”

A fiery flower unfurls on the horizon. From within it emerges a dark blue arrow that pierces the sky, followed by a cloud of white smoke. The ground shakes from the aftershocks. Seconds later, the sonic boom reaches the group. Many of its members are wiping tears without making any effort to hide them – despite the Anglosaxon tradition that discourages public displays of emotion.

And so, in front of my eyes, accompanied by tears and cheers, loaded with blessings and expectations, on January 3, 1999, the Polar Lander left for Mars. After a year of travel, it will touch down on the South Pole of Mars and search for subterranean water.

Why is this mission important? Today Mars is bone-dry, but its surface features betray that it enjoyed liquid water in the past – gullies, wadis and coasts of now-vanished seas are clearly visible in its photos.

Wherever there’s water, there is life. Martian life, if it exists, is almost certainly at the bacterial stage. But if we find it – or just its petrified remains – this will give us the very first proof that we are not alone, that our Universe, vast as it is, may perhaps contain companions.

Such a discovery will overshadow even the upheavals brought about by Copernicus and Darwin. It will break our eternal isolation and force us to completely revise our ideas of the universe and our place in it. The existence of extraterrestrial life will make us understand that we occupy no special place in the universe, that we are observers or fellow travelers and not, by the grace of any god, lords of creation. And it will force us to remember yet again that humanity is a single entity, traveling on a lone ship that makes it way through an indifferent sea.

For a bearer of such a heavy literal and symbolic load, the Polar Lander is miniscule. The size of a small fridge, jam-packed with instruments, it resembles a beetle, with the fragile solar panels standing in for wings. Among other things, it carries a microphone. For the first time, we will hear the sounds of the winds on another planet.

The inventiveness required to put together a space mission is almost unbelievable. As an example, the two tiny instruments that will detect the potential underground water and send the results to the orbiters must achieve the following: land unscathed after enduring the heat of atmospheric entry; pierce like missiles a thick layer of ice without harming their electronic circuits; enter the ground in the correct orientation without rudders, parachutes, engines or further instructions from Earth; and last but not least, do exact measurements with fragile instruments the size of a small human finger. Such demands are the order of the day for NASA’s technical personnel.

The morning before the launch, the engineers and scientists who achieved these miracles explained to us the goals of the mission and the details of the craft and its instruments. All were trembling with tension and fatigue, but their eyes burned with their vision.

These men and women, whose names will never become known or celebrated like those of the astronauts, already dedicated four years of their lives to this mission – and will give as many in the future, analyzing the information sent by the spacecraft. Like the artisans who built Stonehenge, the Pyramids, Aghia Sofia, the Taj Mahal, these people grow old in obscurity, with their only reward the knowledge that will be added to the annals of the species… and with their sole but immense privilege to be the first who glimpse the New Worlds.

Because, in the end, that is the real mission. Exploration of space is the large collective effort of this era that will change all our lives. Not only because we may discover alien life. Closer to home, this exploration is the guarantee for our continuation.

Earth is truly the Garden of Eden, but its magnanimity has spoiled us. Now, having grown used to the caresses of a planet ideal for our needs as well as the luxuries of advanced technology, we have almost exhausted the finite resources of our paradise. With the pressures of the human population, the rest of the biosphere is contracting daily and the quality of life is dwindling for all except the privileged.

It is true that we have not solved our problems here, and inevitably we will take them with us wherever we go. However, if we wait till the last moment to launch the ships with the seeds of terrestrial life, the likelihood of finding another welcoming harbor before we suck our parent planet dry will dwindle to zero. We must prepare for this great step now, while we still have leeway.

All this is felt by those that came to wave farewell to the Lander. That is why they brought their children to share the stargazing, something very unusual for Americans who almost always separate their social activities by age: they want the next generation to remember that this tiny spacecraft and its companions carry our future.

Sojourner, the Lander’s predecessor, was the first to walk on Mars – a kid’s toy cart, which sent us thousands of pictures of the planet’s surface. A famous cartoonist showed it leaving human footprints, and he was right: these miniscule spacecraft, that have opened windows to the universe for us without costing even a millionth of a military aircraft, are the expression of our best selves. And they, along with our radio and television emissions, are our heralds and ambassadors to the unknown.

The day after the launch, the NASA PR office showed us around. The Space Center is within a national forest full of endangered flora and fauna. If the Federal Government had not inadvertently protected it, that entire coast would be a solid cement wall. The paths cross canals full of water lilies where alligators sun themselves. Egrets and cranes fish in the shallows. Above the rioting semi-tropical greenery rise the scaffoldings of the launch pads and the buildings where the spacecraft are built.

The building where the craft undergo final assembly is so large that it creates thermals. As a result, it is constantly circled by a fleet of hawks – a fitting retinue. Its vast interior creates such local temperature gradients that often it rains or fogs. Like an Escher drawing, it teems with skywalks and protrusions that hold entire labs. Looking down from the top you feel like a feather, as though here gravity doesn’t hold sway.

The launch pad that we visited is called Alpha. From there rose the Apollos for their trips to the moon. The pad is a giant Meccano set, a plaything for Titans. The surrounding wire fences are full of holes, from the jagged fragments of asphalt that erupt from the floor whenever it siphons the flames of liftoff.

I bent and took a piece of the worn, burnt asphalt. These scaffoldings don’t launch just spaceships and falcons. Around them fly the dreams of all humanity. This place is sacred, it has received sacrifices – the crew of the first Apollo, the crew of the Challenger, the nameless technicians of the missions. And the deity to whom these offerings are dedicated is Prometheus, who rose against mightier powers. His rebellion made us who we are and brought us here, in pain and in glory.