bioengineering

Editing Out Diseases with the Help of Bioengineering

gregladen — Wed, 15 Feb 2017 18:24:23 +0000

Editing Out Diseases with the Help of Bioengineering

I get a lot of "infographics" and many are quite good. But this medium has become a vehicle for commercial advertising. So, some company comes up with an info graphics, maybe makes a good one, sends it around to the bloggers and such, and thier name, somewhere down there near the bottom, gets around. I don't mind the commercial aspect too much, but unless I'm able to vet the graphic, I can't post it, I don't generally have time or resources to do that, so I therefore ignore them.

But this one I'll post because it looks interesting and is produced by a university. Also, we often discuss GMOs around here, and this is a handy dandy look at how that community sees itself, from an important perspective, at the moment.

So .. (click on it to see it in all its bigness)

Throughout history, humans have continuously made efforts to heal and eradicate diseases. In early, less modern times, this process was considered both difficult and strenuous, but with the advancement of technology and bioengineering, humans are developing faster, more effective measures for treating and eradicating diseases. To learn more, checkout this infographic sponsored by the University of California, Riverside’s

gregladen Wed, 02/15/2017 - 13:24

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The infographic appears to be more marketing propaganda than good medical science. The marketing aspect seems especially pronounced when the historically greatest category (of unintended, secondary harm) is quite literally the last item before the footnotes. This is not generally regarded as appropriate in analysis circles. As for an example of bad science: The first list is labeled as a subset of those "conditions that make" disease eradication "scientifically feasible". This implies conditions in the list are individually necessary, but as a subset they are not collectively sufficient. That's a fair scope limitation we can accept since we don't need a complete list to do good science. However, when we look at each condition, we run into trouble. Consider the first: "Demonstrated elimination in the past". The logical consequence of that condition would be that it excludes any first eradication from being considered "scientifically feasible". This doesn't seem like something we would want to exclude if, as is generally the case, we think good science is often distinguished by firsts. Similar problems flow down the infographic, and it seems to positively advocate HGE. Further, the position layout, shapes, and nearly all other imagery appears included mainly oriented toward artistic goals rather than to facilitate understanding. My personal view is that work should continue until the intersection of good science, effective learning, and attractive presentation is found - which I hope the creators will pursue in subsequent versions.

What I got out of this infographic: University of California doesn't know what a Canadian flag looks like.

Problem Solving Bacteria

kbonham — Wed, 17 Nov 2010 16:55:04 +0000

Problem Solving Bacteria

This is just awesome:

A strain of Escherichia coli bacteria can now solve [sudoku] puzzles
[...]
"Because sudoku has simple rules, we felt that maybe bacteria could solve it for us, as long as we designed a circuit for them to follow," says team leader Ryo Taniuchi.

The mechanism is ingenious and yet straightforward at the same time.

Basically, they have 16 different strains of bacteria, with each initial strain representing a spatial coordinate on a 4x4 grid. Each bacterium has a "4C3 leak" system, which is a chunk of DNA that the team designed that has 4 possible outputs. Depending on incoming signals, different chunks of that DNA will be excised, leaving only 1 output remaining.

Once there is only 1 element left, that bacterium is "differentiated," and starts making viruses that can transmit information about its location and identity. Bacteria strains in the same row, column or section can receive information from that bacterium, but others express special anti-sense RNA sequences that will silence incoming viruses from other locations (this probably doesn't make sense if you've never played sudoku before - you can check out the team's abstract to learn more).

All 16 strains are thrown into a flask to grow together, with a few of the strains pre-differentiated to start the puzzle off - once these have communicated to all of their neighbors, each strain "location" will differentiate and transmit that new information to its neighbors, and the puzzle will solve itself. The information in this culture flask must then be visualized by taking the viruses floating around in the flask and adding them to another set of engineered bacteria which are plated out in a 4x4 grid, and express particularly colored fluorescent proteins.

I think that the viruses and bacteria used in this system can barely even be called viruses and bacteria. We don't call a hammer "shaped steel with a rubber grip," even though that's what it's made from. These "organisms" are so heavily engineered, so sculpted to our ends that they are barely a shadow of their former selves. They are membrane-enclosed tools. And we're only getting better at these sorts of manipulations.

Like I said - awesome.

kbonham Wed, 11/17/2010 - 11:55

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Ahhh, once again this blog gives me the ability to talk about awesome things to people who think I'm way smarter than I actually am.

The experiment that has been carried out is brilliant and this just shows the amount of development that happened in technology.

Like you mentioned, these organism can't exactly be called bacteria or viruses because they have been highly engineered. But this does reveal the scope to use such engineered bacteria to treat viral infections that have been a challenge in the pharmaceutical industry.

that's quite the interesting work

They also pack more punch - compare the ratios of group to phase velocity.

Glenn Reynolds loses his freaking mind: JUST WHAT THE WORLD NEEDS NOW: North Korea fires artillery.

Engineering Hybrid Silks

cagapakis — Thu, 30 Sep 2010 09:33:55 +0000

Engineering Hybrid Silks

There was some big news yesterday in transgenic silk from Notre Dame and the University of Wyoming, where scientists have genetically engineered silkworms to produce silk that is a mixture of spider silk and the regular silkworm stuff. Silkworms produce the strong and versatile silk that is used to make clothes, but spiders produce silk that can be much stronger and much more elastic. Spiders, however, don't like to be grown in huge factories and don't make easily harvested cocoons like silkworms, so gathering even small amounts is very difficult (here's a fun how-to for collecting spider webs into thread). By engineering silkworms to produce spider silk it's possible to make the super-strong protein fibers at an industrial scale, for applications in medicine like super-strong sutures or tissue engineering or even to make bullet-proof vests stronger than kevlar. The engineered silkworms aren't producing 100% spider silk yet, the silkworms are instead engineered with a copy of the spider silk genes fused directly onto the end of the natural silk gene, so that the silkworm produces a silk that is a mix of the two proteins. The spider/worm silk fusion, however, does have many improved properties, and new genetic engineering technologies can potentially improve this even further and create other novel silks not found in nature.

Spider silk isn't just one kind of protein, there are thousands of species of spiders that each produce different silks for different purposes--web weaving, dragline making, egg protecting, or prey capturing. A recent PLoS ONE paper (Agnarsson et al. 2010. Bioprospecting finds the toughest biological material: extraordinary silk from a giant riverine orb spider) describes the discovery of the toughest spider silk found to date produced by "Darwin's bark spider," Caerostris darwini. These spiders form insane webs strung across whole streams, with bridgelines spanning up to fourteen meters. I don't really want to think about spiders being able to somehow fling themselves all the way across rivers on super strong silk threads, but the discovery is amazing and the potential for new biomaterials waiting to be discovered is incredible.

This kind of bioprospecting--surveying nature for compounds and materials with special properties--coupled with bioengineering for sustainable scale-up of production will make it possible to develop new silks specialized for many different purposes. From It Takes 30's post about the discovery of the new spider silk:

Agnarsson et al. argue that it is very likely that yet stronger silks remain to be discovered. The properties of spider silks have only been carefully investigated for a few species, covering only a tiny fraction of the genetic and ecological diversity of spiders. The property you want to measure also depends on the application you have in mind; if you measure toughness at two different rates of pulling, the measurements may not match, and which silk is better may also change. The authors suggest that thinking about the ecological niche a species inhabits may -- as in this case -- provide important clues to finding even more extraordinary biomaterials.

So, one day, police officers may wear (spider) silk shirts instead of Kevlar vests. Much more stylish, if a little predatory in symbolism.

(Thanks to Sri and Brady for the link and It Takes 30 for the typically fascinating post!)

cagapakis Thu, 09/30/2010 - 05:33

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This is also exciting in the context of bioengineering as spider silk is less likely to produce immune reaction than the Bombyx mori silk.

Spider power! >8<

That was supposed to be: >8 <

(stupid html ate my <)

Very cool post.

Silkworms spinning super-strong silk. Nice.

The idea of spiders able to leap 14m will give some of my spider fearing friends the yips. I always liked spiders and welcome the planetary takeover by our arachnid overlords.

IIRC, spiders let the wind anchor their bridge lines, so self-catapaulting spiders needn't haunt anyone's dreams.

This is an absolutely fascinating post - especially the bit about "spider silk shirt". It made me wonder how feasible it would be to use actual spider silk or whether some sort of synthetic material would be made that would have the same properties.

It also made me smile as I know the author is big-time into fibre crafts (as am I) and I know that the craft world is adapting industrial materials all the time to come up with exciting new uses and designs.

Cocoon!

cagapakis — Tue, 27 Apr 2010 09:20:32 +0000

Cocoon!

Silks are incredible protein fibers produced by many different species of insects. Besides their use in making versatile textiles, silks are currently used in many different medical and engineering applications, from sutures to tissue engineering scaffolds to flexible electrode brain implants. Since I love fabrics and I'm interested in what biological engineers can do with biomaterials, I recently started working on a fun side project to raise and engineer silkworms, the animals used in industrial silk production around the world. We're having a lot of fun learning about silk and how to raise such macro-organisms when we're used to bacteria. Watching them grow from tiny hatchlings to enormous (finger-sized) worms ready to cocoon has been pretty amazing.

The worms aren't actually worms at all, but the larval stage of a moth. The cocoon is made out of a single mile-long strand of silk that protects the animal during its transformation into a moth. The actual process of making the silk cocoon is incredible, here is a time-lapse movie one of my colleagues made of the 24-hour long process:

cagapakis Tue, 04/27/2010 - 05:20

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Silk worms and cacoons?

your insane.

How technology can drive down health care costs

revere — Sun, 18 Apr 2010 12:29:19 +0000

How technology can drive down health care costs

With health care costs growing without bounds, the medical devices industry and President Obama are hard at work. Not hard at work reducing costs. Hard at work convincing us that the solution to the cost crisis is more technology. Right, Mr. President. And John McCain is a maverick and Sarah Palin is a genius. Almost everyone else believes advanced technology is a significant driver of health care costs and the idea that it will drive down costs is not just a fantasy but steaming pile of crap. That doesn't mean there's no room for innovation to lower costs. On the contrary:

Nobody knows precisely why it works, but doctors have known for decades that the healing process for open wounds can be greatly speeded up by applying negative pressure — that is, suction — under a bandage sealed tightly over the affected area. The speculation is that it helps by drawing bacteria and fluid away from the wound, keeping it cleaner.
For patients, there is a benefit even beyond the speedier healing. Traditional dressings need to be removed and replaced — sometimes painfully — up to three times a day, but with the negative pressure system dressings can be left in place for a few days. But in the developing world, there's a problem: The systems are expensive, and they need to be plugged in or powered by batteries that last only a few hours. In many developing nations, a reliable source of electricity is rarely available.

[snip]

The device, a cylinder with accordion-like folds, is squeezed to create the suction, and then left in place, connected to the underside of the wound dressing by a thin plastic tube. At that point, it requires no further attention: "It holds its pressure for as long as there's not an air leak," [MIT Masters Degree student Danielle] Zurovcik explains. For that reason, a suitable dressing that can hold the seal is a crucial element of the system. (MIT News Office, h/t Boingboing)

If this is such a good idea, how come some high entrepreneur hasn't made such a device? Apparently they have. You can rent one for $100 a day, but the batteries have to be recharged every 6 hours. Or you can try something like this, where each unit costs about $3 and doesn't require and power or attendance. It was designed by a class of student engineers and developed further for a Masters degree by one of them. It's been field tested and is being refined further to improve the dressing seal. There are already plans to manufacture it locally in Rwanda in an ambulatory version small enough to carry in a pocket.

There is a lot of scope for reduced cost technology, even in the high tech area. Recently we were interested in using x-ray fluorescence (XRF) for exposure estimation in an epidemiological study. We have a device but it costs around $30,000. It seems it isn't much more than an x-ray source and a detector with suitable ancillary circuitry. Asking around it sounds like something an undergraduate electrical engineering student could build for under $1000. We're looking into it.

While the difference between $30,000 and $1000 seems an improbable gap, consider the difference between $100 a day and $3 to purchase in perpetuity. Technology might very well drive down costs. But not the way we are going about it via private sector entrepreneurs and venture capitalists hoping to milk the health care cash cow.

How about some open source health care technology projects?

revere Sun, 04/18/2010 - 08:29

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As a database guy I can tell you they're looking to find commonalities among varying diseases and issues. Whether that will lead to improved treatment is up in the air at this point.

How does the suction device described (the accordion-like folds one) differ from the drains routinely placed in surgical wounds?

Keith: Drains aren't under negative pressure.

How about some open source health care technology projects?

All well and good if it's going to be manufactured and used in Rwanda. To market it in the USA it you're up against the usual barriers to entry into the healthcare products market, where the up-front expenses are prohibitive unless you can promise a backer brazillions.

That's assuming that some can't-stop-doing it inventor like Steve Wozniak does it on donated time. If you're looking for an academic project (e.g. undergraduate engineering class) you're up against Bayh-Dole and the institutional requirement that the University control it and be able to successfully market it (see "backer" above.)

The ones they've stuck in me on several occasions were under negative pressure. A daily activity, nurse opens them, air goes in with a hiss, they expand, nurse empties them and measures the amount of yuck coming out, compresses them and seals. They expand slowly until the next day's "doing the drains". The actual sucking bits vary in diameter from about 2cm (with a very thin tube) to 10cm (with a 16 or 20 french tube). Expanded they are about as long as their diameter, compressed about one fifth of that. Generally, depending on the amount of yuck, they don't expand much in 24 hours, so they are still under noticable negative pressure the next day.

I totally agree. Private industry and profit motive make for awful health care, all the way down to actual patient care.

There is also the issue of top down decision making structures, where the people who make decisions about what to buy or how to do something are rarely the people who actually know the work. This is a problem in most industries, but still worth examining IMO.

I like the idea. I know people who would be delighted to work on such things but they will feel really burned when a major corporation steals their elegant idea, jacks up the price and makes a brazillion dollars off of it.

How can this be prevented with respect to open source technology?

Perhaps if it is patented? But the corps have ways around patents by making minor changes in the product and patenting them. However, if the idea catches on and open source is cheaper that may propel it forward. Still, with the government plans mandating brand name meds over generic (I sometimes have to do a prior approval to get my medicaid patients available generic meds, no review required for brand) one wonders if the cheapest alternative is really what they want.

nuf said.

The accordion design is one of the most elegant pieces of engineering solutions I've seen - you've got to love the beautiful minds at MIT who conceived it.
On the side of reducing costs, the most recent Science Show on ABC (http://www.abc.net.au/rn/podcast/feeds/science.xml) covers an interesting theory that the immune system is subject to cycles and, that the timing of certain treatments may have an impact on their efficacy; and cost.

I think we need to make a distinction between "device technology" and "information technology".
Device technology has been a major driver of costs and due to the way health care in the US is funded is a scam... i.e. MRI in France $250 and in the US $2500.
Information technology has the potential to lower costs by providing better information at the point of care and for operational research. (However, most health care software is poorly designed from just about every aspect resulting in higher costs, frustration, and reduced benefit.)

There are groups of people doing open projects for medical stuff. The one that comes to mind is an open EEG system. I know there are people at https://www.noisebridge.net/wiki/Noisebridge working on just that.

i played nursemaid to a friend who underwent reconstructive chest surgery a couple years ago, and those drains were also under negative pressure --- same sort of rubber-bladder, empty once or twice daily and measure the output affair that Keith Harwood described. emptying them were part of what i helped with, in fact.

I've just looked at the reference to the MIT device. It looks, except for the colour and being rather more robust, pretty much like the ones I had. But, when were the MIT ones invented? The text is dated 2010 and reads as though the invention was recent. A date of '07 is in the text, but it's not clear that that relates to the invention or the inventor.

However, I got my first lot in 2004 and at the time I got the impression that they were standard operating procedure, not new, not experimental, this is the way we always do it. So either these are not known to the MIT students and American medical practice or the MIT article is much older than it appears.

If you love the idea of producing a $1,000 version of a $30,000 machine, then check out what is going on in Africa, at http://www.afrigadget.com/ - a home-made welding machine, for example, or a lamp made of a couple of batteries, a cut up flip-flop, and a milk can - mostly from the low income (aka slum) areas of Nairobi. These guys could probably do it for you, and from scrap metal and junk! Enjoy the ingenuity!

great post, great point. people are motivated by incentives. people get sold on tech factor. to prevent sacr tissue post-ACL reconstruction, they home-delivered a gismo that you set your leg on, and it scissors your leg, at the knee, up and down continually. It was a metal frame, with hinged deelio for knee, fake lambs-wool for comfort, actuator, electric motor, cord, and transformer.

Spec that your self. Max $500?

What was my insurance co. charged?

$1,000 RENTAL for one week.

For grins, I got on the web and clicked in a Mercedes rental for one week, local pickup and delivery.

Yes. $1,000.

For the same $$, I could have sat in a Mercedes, operating the seat-moving thingio back and forth, enjoyed heated seating, the awesome stereo, leather seats, etc.

How can Enterprise rent me that car for a week, and the medical equipment renter "requires" the same dollars?

Because each of us is spending other people's money.

My premiums have already been paid. So, it is not my money.

The doc orders, but does not pay.

The ins company does not lose: it is just income/outgo ratio, and they raise rates as outgo gets higher.

The rental company covers their cost to buy the machine - obviously, they have to be clearing way more than Enterprise rent-a-car is doing on the Mercedes.

In the distant future, health care reform could address some of these issues. But from my studying the plan, I don't see the direct way we will reap great savings from technology.

Rationality as innovation

revere — Wed, 31 Mar 2010 04:09:25 +0000

Rationality as innovation

The Department of Homeland Security (DHS) Secretary Janet Napolitano is asking academics to work with her agency to develop "innovative initiatives" to protect the nation from terrorist threats. This is what I would call a faith-based initiative, in this case, faith in the technological fix. DHS could certainly use some help. It's one of the most clueless and incompetent agency in the federal government. But I don't think the answer to the problem is going to be found in nanotechnology, computer science or micrcomputer circuitry:

The DHS noted that the cooperation between its departments and the science community has already resulted in major innovations in developing state-of-the-art screening, bio-threat detection and other technologies.

These results are already deployed across the country—including equipment such as advanced imaging and explosives trace detection technologies designed to protect the traveling public from threats of terrorism at U.S. airports. (Tejinder Singh, AHN)

Pause. OK. I've stopped laughing uncontrollably while I was putting my shoes back on.

Of course for any tech fix there is some easy work around. Ask the computer security industry or the record industry. If you want to stop terrorism you have to stop people from wanting to kill themselves and other people. There are reasons why these acts are carried out and while solving them would bring us into conflict with powerful interests like the oil and energy companies or the hard right nutcases running Israel or Hamas, they are rationally solvable.

Using rationality to solve the terrorism problem? That would be innovative.

revere Wed, 03/31/2010 - 00:09

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Here is a MIT and Harvard discovery that I think goes along with (DHS) request.

Magnets Can Manipulate Morality
Magnetic fields targeting the moral center of the brain could scramble our sense of right and wrong.

THE GIST:

* Strong magnetic fields could affect moral judgment.
* Targeted magnetic fields can make people more inclined to judge outcomes, not intentions.
* The findings could have implications for neuroscience, as well as the legal system.

Magnets can alter a person's sense of morality, according to a new report in the Proceedings of the National Academy of Sciences.

Using a powerful magnetic field, scientists from MIT, Harvard University and Beth Israel Deaconess Medical Center are able to scramble the moral center of the brain, making it more difficult for people to separate innocent intentions from harmful outcomes. The research could have big implications for not only neuroscientists, but also for judges and juries.

Related Links:

* Brain 'Hears' Sound of Silence
* Does Insomnia Shrink Your Brain?
* HowStuffWorks.com: Brain Mapping
* Brain Waves Surge Moments Before Death

at
http://news.discovery.com/tech/magnet-brain-morality.html

Snowy

Thank you

http://scienceblogs.com/

Nothing like abandoning the women of Afghanistan to the tender mercies of a resurgent Taliban as a rational response to terrorism.

Also, don't forget, (I'm going to assume Chomsky and Zinn didn't tell you this) had Atta and Bin Laden called off the 9-11 attacks on 9-10, American forces would be enjoying more time with their families and we'd be enjoying smaller budget shortfalls. We went into Afghanistan after we were attacked on 9-11, not because of some imperialist design.

@History Punk

Osama bin Laden is a Saudi. He was hiding in Afghanistan. Had he been hiding in Paris, would we have invaded France?

You'll remember your history: the Taliban were Ronald Reagan's Freedom Fighters, "the moral equivalent of our founding fathers". The CIA created the Taliban to make it impossible for an invading army to successfully occupy the country, back when the enemy was the Soviet Union. Now we are fighting the CIA's success story? Why?

We invaded Afghanistan because the contractors who make money from war wanted to make more money from war. Corporations make US foreign policy.

The Freedom fighters Reagan was referring to were the Contras if I remember correctly.

After the Soviet armies left Afghanistan, the CIA-funded mujahadeen began fighting among themselves. It was this chaos (long after Reagan left office) that led to the rise of the Taliban. If any country can be blamed for creating them it would be Pakistan (through their intelligence service).

Revere:

By your argument it sounds like we should eliminate all our police forces (after all, they are pretty incompetent just like DHS), and focus our resources solely on education, psychological counseling and economic opportunity. Will that be your next blog post?

You sarcasm and cynicism about our government's efforts to improve our security is unbecoming and stinks of TeaPartyism. Given that we will never live in a perfect world (or do you really believe that is attainable???), it seems quite reasonable for our government to continue to develop technologies and strategies to minimize the effectiveness and success rate of terrorists. Who else will do this? You sound much closer to a faith-based worldview than Napolitano.

To overcome advanced security technology requires terrorists to have technological and organizational sophistication that must be deployed in absolute secrecy to be successful (and it will likely work only once). Government efforts to keep ahead of terrorists' technological capabilities are particularly effective against the less sophisticated terrorist organizations and individuals, which constitute the vast majority. Thus these efforts are both necessary and effective. But perfect? No.

Revere, you do not have a better idea, do you?

Jonorom: Why does it suggest we get rid of the police? And why do you think they are on average incompetent. I've had experience with both DHS and the police, and while they do different jobs, DHS doesn't do its job anywhere as well as most police do theirs. As for the TeaPartysm remark, it makes no sense. If I think DHS is incompetent does that mean I think there is no role for government in health care or even national security? Not a logical inference. As for the ability of technology to protect us, it is limited. Computer security people, who are far more sophisticated, know that. And your thought that individuals don't have the sophistication needed doesn't seem to be the argument that DHS uses for bioterrorism, which require far more sophistication than bombs and guns. Do I have a better idea? Yes. Adopt a foreign policy that makes sense. Obama hasn't done that yet and Bush's foreign policy may have been the greatest debacle in the country's history. The terrorism problem is one consequence, for Russia as for the US.

"Osama bin Laden is a Saudi. He was hiding in Afghanistan. Had he been hiding in Paris, would we have invaded France?"

Yes, if France, like the Taliban, had refused to prosecute him themselves or denied our requests for extradition. However, France is a sane democracy, so there was little risk of eitehr happening.

"You'll remember your history: the Taliban were Ronald Reagan's Freedom Fighters, "the moral equivalent of our founding fathers". The CIA created the Taliban to make it impossible for an invading army to successfully occupy the country, back when the enemy was the Soviet Union. Now we are fighting the CIA's success story? Why?"

I know my history so I am aware that the Taliban was organized in 1994, long after the CIA lost interest in Afghanistan. I also know that the United States' "Freedom Fighters" in Afghanistan were divided. Some did join the Taliban, however some, fearing the imposition of an Islamist regime that would make them behave, like Masood, joined the Northern Alliance.

"We invaded Afghanistan because the contractors who make money from war wanted to make more money from war. Corporations make US foreign policy."

For the mentioned gibberish to make the least sense, there would have to be a reason the power elite were able to mobilize Afghanistan and noy Syria, Oman, or Australia. Now, I am sane, so I'd suggest that 9-11 was that reason. But clearly corporations can dictate declarations of war against random nations, despite a powerful, gun-shy military, a general public that dislikes foreign adventures, and politicians who fear another Somalia.

There is a saying up-here in QuÃ©bec,

One's liberty ends where the other ones start.

We should be able to understand with our consciousness to grasp the fact that if we do not solve injustices, imperialism and arrogance we are just simply doomed.

Why the 24 hours medias do not give an hour of prime time to educate people not from a propaganda point of view but from a collective Humanitarian point of view.

Maybe the concept, 'If it bleeds it leads' is after all a chimeria.

At least some should have the courage to give it a try.

Snowy

What we really, really need are itsy-bitsy nano-spy watchbugs that can creep in through the bloodstream and cross the brain barrier to read those "thoughts" even when hid behind the philosopho-barrier separating "neuro" from "mind." Then also we can spin the mags a bit to change them (change ideas). Actually, that magnet article is pretty scary; I mean, let's remagnetize the whole cerebellum and see what we get. . .oh sorry.

Pretty scary allright these magnets, on top of it, it fits well under an helmet or a uniform hat.

That cooperation between the DHS and science community involves money for grants, and the technology is developed by private corporations taking a profit on their sales to the DHS. The latest feeble attempt by the underwear bomber was good for this business.

The fixation on airports and planes is curious to me, assuming the official explanation on terrorism to be true.
The point of terrorism it would seem to me would be to instill terror in the maximum number of people. Limiting operations to airports is inconsistent with this premise. Of course, if you wanted limited terror with minimal damage, this approach would make sense. But why would AQ want this?

Despite the GWOT, the drug trade is booming. Drugs still cross our borders, money still gets laundered, over 1 billion dollars a year according to estimates, although the actual amount may be higher. Yet the terrorists do not exploit this, and instead focus on the most secure target which presents the maximum resistance, instead of adjusting and taking the path of least resistance. Maybe they are just dumb, which is a good thing.

Once across the border of course, obtaining weapons is hardly a problem with our loose gun laws. I can imagine numerous scenarios which I will not mention for obvious reasons that could cause more terror than some guy blowing up his underwear at 30,000 ft.

So what are we to make of this. 9/11 was certainly real, we saw this live, so there are terrorists. But who are they actually. I don't mean those who execute the attacks, you can always find young disgruntled men and women and feed their hate to get them to do bad things, but those who plan and enable the attackers, and for what purpose?

The official and popular belief is that it is Al Qaeda leadership, who hate our way of life, and are against Israel and our support for their treatment of the Palestinians. But most of us hate or disagree with something or another, but are not compelled to fight. Only when it is close to home do we get riled up enough to fight. But maybe it's true.

One needs to consider how AQ came into existence though. To add to the history discussion one must agree that AQ is not the Taliban, and those who make up AQ were trained in 1979 onward to be resistance fighters to destabilize Russian occupied Afghanistan. Actually, they were being trained 6 months before the invasion. Is the connection really broken, or is AQ simply a useful tool for those who wish to instill terror for domestic reasons. If not, how did we go from being friends to foes, and hated so much. I mean, Israel was not treating the Palestinians any better in 1979 than in 2001.

It is interesting, and perhaps not coincidental, that at this same time, the Ayatollah was allowed to leave France (after residing in Iraq) for Iran and topple the US supported Shah, leading to the first Islamist state (Islamic fundamentalist government). It is also interesting that Irans military, which was well supported by the US was told not to intervene and support the Shah at the risk of losing the ability to procure arms and replacement parts for their equipment. As the Iran-Contra arms sales shows, military sales continued. Promises kept.

It was shortly after the Ayatollah took over, that our then friend Saddam Hussein was led to believe the time was right to invade Iran (this was repeated 10 years later when he invaded Kuwait thinking he had the green light from the US). Thus began a great war. The US funded both sides of the war, since both sides needed weapons to continue killing each other, and that Iranian backed Kurdish resistance in the North was stopped with chemical weapons, the ingredients sold by the US (which was why Saddam was not tried for crimes agaisnt the Kurds). At the end of this war, Saddam was greatly weakened, as was Iran.

Most folks don't know since it is not reported much was that Israel had a plan to Balkanize the Middle east, this plan was published in 1982 as Israel invaded Lebanon, an act which led to the defacto breakup of Lebanon with Shia control of the south by the newly created Hizbollah, funded by the Ayatollah.

Break it up into small pieces so the Arab world could not unite under one leader or government as in the Ottoman Empire. Divide and Rule. This was the best security strategy for Israel, and it's likely that the US agreed with it and this strategy played a role in Iran, Iraq and Afghanistan in 1979 and today.

Our invasion of Iraq in 2003 had nothing to do with Al Qaeda, but to ensure Iraq would be broken up, and it has been broken up into 3 zones after a prolonged period of ethnic cleansing (Kurds, Shia and Sunni controlled). Iran is next.

After the Soviets left Afghanistan, before their break up, some of those resistance fighters went on and fought for the various factions in Afghanistan seeking control, and some did indeed go over to the Taliban. BTW, the Talibans religous practices were not new to Afghanistan, just read Micheners book "The Caravaan". The US did not oppose the Talibans take-over since it was felt this was the best chance for Afghanistan to be stabilized and allow the building of an oil pipeline between the Caspian sea and India.

The official reason to invade Afghanistan is hard to refute. Obviously, it is hard to argue that overthrowing the Taliban and weeding out Al Qaeda after 9/11 was a bad thing. But there were other reasons, perhaps the main ones.

First Afghanistan has a geostrategic importance. Located next to Iran and Pakistan, with routes to Russia and China. Should war break out in any of those places, having bases and troops in Afghanistan would be convenient.

It is an important future energy route from the Caspian Sea to the East which we would like to control.

And then there is the opium. The Taliban had all bet crushed the opium business, today it is much larger than ever before, supplying 95% of the globes global sales, with enough surplus to double the supply. Drugs are a weapon which are can used against your opponents. Drug addicts don't meake good fighters, and are not productive members of society. It is also a great way to fund covert operations.

Back to Al Qaeda, some of those fighters were recruited to fight in Bosnia in the 1990's, destabilizing the former Yugoslavia which led to NATO's 1998 war against the Serbs. As a result, today we have one of our largest bases globally in Kosovo. This is a convenient location to serve as a base to protect/control energy routes to Europe from the East.

Other resistance fighters fled to different parts of the world after the Soviets left Afghanistan, including OBL, kicked out of Saudi Arabia, on to Yemen and then to Afghanistan with the permission of the Taliban. These are who we refer to as AQ.

OBL from all accounts is still alive and kicking, somewhere, making his videos and tapes. I sometimes wonder if he has a production studio in Crawford TX. I jest of course.

History Punk -- You may also recall that the Bush Administration gave the Taliban in the realm of $30 million dollars in May of 2001, in recognition of their efforts in curtailing the heroin trade. This was with full knowledge of their atrocious treatment of women. Everyone knew, but few but Americans other than women's rights organizations cared.

Funny how suddenly on September 12, 2001, Americans suddenly gave so much of a damn about the rights of Afghan women. Give me a break.

caia,

So because the United States failed to stand up for the women of Afghanistan before 9-11 and gave token support to the Taliban for doing something good for Americans, we should now throw them to the wolves that are the Taliban and Al-Qaeda? Nice.

"Back to Al Qaeda, some of those fighters were recruited to fight in Bosnia in the 1990's, destabilizing the former Yugoslavia which led to NATO's 1998 war against the Serbs. As a result, today we have one of our largest bases globally in Kosovo."

Serbian propaganda aside, Al-Qaeda was a limited force in both Bosnia and Kosovo. Camp Bondsteel (that base in Kosovo) exists because Serbian forces rampaged through Kosovo in an effort to drive the Albanians out in 1999. It was on TV non-stop for 79 days. Surely you saw the massive trail of refugees fleeing Serbian marauders. Right?

find new flu-drugs and vaccines, prepare cities for full respiratory protection
before some terrorist gets the idea of reassorting Eurasian and American
Swine/Turkey/ flus. We just saw how easy it is to create a pandemic.

While their faith in techno-fixes may be misplaced, your faith in finding rational fixes is at least as naive.

The causes of terrorism are often not rational and appeasing the demands of terrorists is often not an option, whether they be home-grown Chrisitian militias intent on attacking The Brotherhood by killing a randomly chosen police officer and attacking the funeral, or an Islamist fundamentalist intent on imposing a new Caliphate.

Converting them to your active form disbelief is also not a realistic solution.

You have previously wisely pointed out how, statistically, terror attacks on an airplane are extremely rare, and how in reality even a small false positive rate for screening for explosives et al will result in many many more false positives than true positives (Bayes and all). The same sort of logic applies the other way. In our very connected world it only takes a tiny percentage of crazies to cause harm. Even if rational solutions could appease 99% of those with what you and I believe are irrational beliefs (which, let's face it, is most of the rest of the world's population) that still leaves many many millions unappeased and of those many who have the ability to come together to attack the rest of us.

That which is just should be done (even though we may disagree about that what is just) but because it is just, not because doing so will protect us from the world's nutjobs; it won't.

Don: You misunderstand. I think rationality would be nice but I don't expect it. On the other hand, getting at the root causes of terrorism isn't so mysterious or the fixes so hard to see. Settling the Israeli-Palestinian problem would be a huge step forward. Right now it is being held hostage by US and Israeli politics. Then getting US military out of the Mid East would be a second huge step forward. Those are two rational acts that would do much to reduce the roots of terrorism. What I find naive is the thought it could be done any other way.

Just because we disagree does not mean I misunderstand. In this case I believe you do.

Let us assume that a solution to the Israeli-Palestinian problem is mutually agreed to by the major power brokers on each side and signed off on by each of those sides. Do you believe that the most extreme elements of each side would uniformly say "Well okay then. That's that." Or would they perhaps continue to resort to violent acts? Maybe even ramp them up some? "There are reasons why these acts are carried out" is true enough; the assumption that those are rational reasons, or reasons that can be addressed by providing whatever it is that you or I would call a just solution (and of course everyone has a different opinion about what that would be) is the part that is naive. Simplistic even.

Don: I said you didn't understand me, not because you disagreed, but because your version of what I said was not correct. And as for your counter comment, it is ambiguous. Do you believe I don't understand you or don't understand the situation? If the former, I'll just say I disagree with you. As for the latter, it is, alas, a question where coming to a mutual understanding is elusive. Your position seems to be that no solution is possible because there are people on each side that will never understand each other. Probably, true. Are we to let them govern the situation? If the answer is no, then we should do something about it. If the answer is yes, then we should stop taking sides since both sides are culpable. Why is a crazy irrational vicious Jew any different than a crazy, irrational vicious Palestinian and why should I prefer one to the other. For my part I don't, so I don't know why we are continually taking the side of one but not the other. That's the kind of more rational response I think would decrease terrorist acts against Americans, which is what the post was about. I also think it would decrease terrorist acts against Israelis and Palestinians, so it's a win-win in my book. And getting out of the Middle East would also be a big step. And a rational one. And do more than taking off my shoes at the airport to make me safe. Of course almost anything beats taking off my shoes. I won't accuse you of being naive since you clearly pride yourself in your realism. One person's realism is another person's naivetÃ©, I guess.

Revere, Don--You both make excellent and not particularly divergent points, but also some questionable ones. Revere in particular, it is naive to assume that resolving the Israel-Palestine issues "justly" would much stop terrorism, since (1) war is terrorism too, and (2) less sophistically (though (1) is not solely sophistic), oil seems more likely than that conflict to be the key to US Mideast military presence. The more important point, though, is this throwing around of "irrational" regarding "terrorists." Yes, violence has its irrational aspects, but lots of actions are violent, and people do stick out their claws to fight back.

Paula: Both issues, the Palestinian one and US occupation of the Middle East are given as the reasons for actions against the US. Support for Israel's war on the Palestinians and occupation of Iraq and Afghanistan are things that would meliorate if not eliminate threats against the US. Both are their objectives and while I don't advocate "giving in" to unjust demands, in this case, both demands seem to me both just and in everyone's interest, including the interests of average Israelis, Palestinians, Iraqis and Afghans, although not, of course, in the interest of Afghani and Iraqi kleptocrats and murderous and deranged Palestinians and Israelis now in control of their respective governments in Tel Aviv and Gaza. If the question is what rationale actions can be taken to decrease the threat of terrorism, it isn't better technology.

My first point is that solution, no matter how just either you or I think it is, will appease the most extreme on both sides. That is not a reason to not aim for a just solution (again acknowledging that we each may have different answers as to what that just solution is and how to get there). A just solution is no more a cure-all for terror attacks than is technology. Those with extreme views will not be appeased by that which either of us believe is justice.

Also my humble opinion is that there is more at stake in the Arab world than Arab sympathies for their brethren Palestinians or the American presence in the ME. There is a battle between those who would have the Arab world join the world's community of communities and accept some basic secular precepts that others are allowed to believe differently or not at all, and those who would create an insular world according to Islamic fundamentalist laws. In that battle the Israeli issue and the American presence are useful props but not the issue and terror is used to sucker the props to be useful tools, providing an "other" to rally against. Yet that only captures one small level to the complexity that includes religion, tyranny, energy, and a variety of tribal identities.

I'll like to Land here Revere, please

Intro in a Nutshell,

You have two Aborigals Genes and Cultures. Scottish and mostly French Genes and Cultures, add it up Jew and Sikhs Genes and Culrures.

There are two Oriental Historical Precedent to Revere Lamp Light Significances,

One in Persia and the other in Kaboul.

Nota:
Sadly Western Academician are not muvh knowledgeable of Oriental History, I presume it is mainly due to the fact that in Orient the Historical Experiences are integrated in Religions and thus disregard by Cartesian Minds.

That being said, I take this opportunity to present my sincere thanks to Revere for His Encyclopedic Oeuvre.

Gengis Khan introduce the Light, implacable new hight tech arm, a new kind of Sword.

Now few centuries later in Kaboul, Afghanistan; there is a sanguinary Muslim Emperor named Aurangzeb.

Northern India is the pray of barbaric coordonnated army invasions and massacrers in the name of ''Allah''.

The Mission to get Nanak, known in Islam as the Pir of India, alive and in prison was succesfull.

To his Letter to Aurangzeb Emperor, from memory here,

He used the Karam of Kabir, an outmost respect Inspired Islamists and it is via the Coran itself that Nanak made a very Harsh Critic to Aurangzeb the shamefull Moslim.

Nanak letter shook so much Aurangzeb that his military and Social Policies changed, saving thus hundreds of millions Innocents.

The point I try to make is that ''Frankness, Respect, getting into the Foreign Context and find solutions, ajustments, formal and informal Understandings.

The whole ''Informal'' activities are not solely Foreign Policy it is a Universal Force called 'Understanding and ajust in respect of mutually favorable narrow relations.

Snowy

Nanak Universal Message was dont twist your proposed Spiritual Values.

When people will live on love

http://www.youtube.com/watch?v=DTi3GfOv4ms&feature=related

Kim Phuc, the little girl lives up here and is now A Peace Ambassador.
She is known to be a International Icon .

For those who understand French
#
Par 4 chemins/Transcription de l'Ã©mission du 3 septembre 2000/Le ...

... Kim Phuc Phan Thi, 9 ans, court pour Ã©chapper aux bombes au napalm
(8 juin 1972), Ils avaient pour invitÃ©e une victime d'une ...

www.radio-canada.ca/par4/Mag/20000903/vb/victimologie.html - 10k - 1972-06-01

The Long Road To Forgiveness by Kim Phuc
http://www.youtube.com/watch?v=Qh3tskrAYuE

Is biotech a security problem?

revere — Wed, 08 Apr 2009 05:05:10 +0000

Is biotech a security problem?

A Reuters piece under the headline, "Biotechnology Boom Raises Security Fears: Mild Diseases Could Be Turned Into Deadly Ones, Experts Caution" we see the biotech Frankenstein/terrorist bogeyman raised once again by "experts" in the area at a scientific conference in Casablanca. The weekend conference was run by a tiny group (budget of less than $250K) with a big name, the International Council for the Life Sciences (ICLS). Their sole mission is biological biosecurity, so it is understandable that their conclusion is that this is a big problem. But is it?

On the surface the proposition is plausible. Rapid advances in biotechnology now allow things to be done that could not be done previously, or allow them to be done much more quickly. Biotech is a largely unregulated industry and who knows what goes on in academic laboratories. The picture ILSI paints is frightening:

"There are so many advances in bacteriology and gene sequencing leading to the possibility of designing genes -- that is what is driving the concern," said Tim Trevan of the International Council for the Life Sciences (ICLS).

Organisms could be genetically manipulated to defeat vaccines, mild diseases could be turned into deadly ones and lethal viruses and bacteria might be created from scratch.

Equipment such as micro-reactors, flow reactors and disposable reactors to produce useable volumes of complex molecules were not even available 10 years ago.

"You want something very infectious if you aim to bring down society," said Trevan. "Whether you kill people or incapacitate them it doesn't really matter, as long as there is a major effect. This could all theoretically be engineered genetically." (Tom Pfeiffer, Reuters)

There as always been a laboratory to defeat vaccines and take mild infections and turn them into deadly ones. It's called Nature and it is very efficient. It is also a very secure laboratory. We don't know most of Nature's secrets yet, particularly the ones that make a bug dangerous. After a lot of intensive investigation by some of the best laboratories in the world we still don't know what makes a flu virus transmissible or especially virulent. Nature knows, but we don't. Now suppose we decide that this is dangerous knowledge. Are we going to start putting up barriers to the dissemination of knowledge about basic flu science? Because if we are, I will give you an ironclad guarantee that it will make us less safe. I've seen too much good work done by scientists sponsored by the military where a General decides that it's too important to tell anybody about. They are usually (always?) wrong about this. I note that the head of ILSI was an inspector in Iraq who thought Saddam had chemical and biological weapons of mass destruction, too. But that's another story.

The idea that there are all sorts of people out there wanting to "bring down society" (What does that even mean) also doesn't make sense. Terrorists use terror weapons for political ends, to bring about some desired event or action. Unleashing a disease that appears to be of natural origin wouldn't do that. It might create terror and chaos, but it couldn't be sure of causing any particular action and would have significant blowback potential on the perpetrators. Perhaps the real motive in promoting this scenario is to prevent a PR blowback, not a biological one:

"If there is a serious, catastrophic incident involving the use of biotechnology, that will hold up the science like Chernobyl did with nuclear," said Taylor. "That's why we need to worry now."

I'm not sure why a possible effect on biotech is something we need to worry about especially, but it is unlikely in any event. The anthrax did have a catastrophic effect but didn't do much harm to biotech and in fact gave a stimulus to the bioterrorism industry, which exploited it for everything it could, despite the fact that the weaponized anhrax came out of one of those labs. The actual situation is the one unwittingly uttered by one of the "experts":

"The thinking is out there and it is naive to assume some people are not exploiting available technology," said Taylor.

That's exactly what terrorists are doing. They aren't fooling around with untested science that is extremely difficult and not likely to succeed. They are exploiting available terror technology, which is frighteningly abundant: guns and bombs. Cheap, effective, accessible. But apparently no one wants to regulate them.

revere Wed, 04/08/2009 - 01:05

Tags

bioengineering

bioterrorism

Categories

Technology

Excellent post!

Ditto!!

I would worry and be very vigilant about the unique economic consequences as a result of a Foot and Mouth outbreak in North America.

While I share your caution around creating 'security risks' where none exist, and overly burdening the scientific community with regulation, there are a number of questions surrounding emerging technologies that are troublesome.

The creation of a hypervirulent (vaccine defeating) mousepox virus through the introduction of an IL-4 expressing gene is a good example of potentially dangerous science. Expanding the host range of a bat SARS virus to include mice as was reported in PNAS last year is another. The resurrection of the 1918 flu, long since naturally extinct, another case.

All of these had purported medical benefits. But they also create access to an organism which has the potential for high levels of destruction. Now these organisms are unlikely to be used/created by the 'terrorist from central casting', but as USAMRIID shows they can be used by disgruntled or unbalanced scientists themselves.

Regulation of these technologies may not be the answer, in fact, I would argue that it most certainly is not. Yet, that doesn't diminish the responsibility of scientists to discuss the ethical/security implications of their work. It is neither helpful, nor ethical, to suggest that science should be left to its own devices pursuing 'truths' regardless of their impact on society.

One has to remember that life science has no 'Bulletin of the Atomic Scientists', despite that fact that it deals with phenomena which are potentially as dangerous. Groups like ICLS play an important awareness-raising role and, I suspect, would generally never favour regulations where the clear collective action of scientists could do the same or better job.

Rieux: I agree and disagree. I am of the view that reconstructing the 1918 virus was a worthwhile thing to do because of what we can learn about pandemic flu and what makes it. I do agree that leaving the ethics of science to scientists is not a good thing to do, but this post wasn't about the general topic but this specific topic. While there is a possible scenario where harmful things can be created in the lab (in fact it happens whenever there is a lab accident), the tech fix for this is invariably worse than the problem if it involves obstructing what most people would consider beneficial or potentially beneficial knowledge (which is most medical research). I'm for discussions of social responsibility among scientists. In fact I've been part of that movement for 40 years and was active in the recombinant DNA debate on that subject. But this post is about this subject, not the subject of social responsibility in general.

I wrote a post the day before about the proliferation of high containment labs that goes to the point of making access to terrorists of agent they could never have access to (in fact I've written about this many times, here). But bioweapons research is research with military or counter-military intent that will have unintended consequences regarding making us safer -- for reasons you identify.

revere,

I think you really underestimate the changes that have occurred in molecular biology within the last few years. Creating novel constructs used to require large amounts of time and money. Importantly, creating such constructs required access to the original nucleic acid one was attempting to modify. This is no longer true. I can now copy and paste DNA sequences on my computer to create whatever construct I wish. I can then email the sequence to a company that will send me back a synthesised construct to my exact specifications. Neither they nor I require the original nucleic acid, sequence is sufficient. Google "DNA synthesis" and you will be amazed by what you find. With this approach, it would be possible to create a virus with whatever genes you choose. For example, people no longer require access to the polio virus to make polio virus. Think about that and it apply that thought to other viruses.

Your suggestion that only people who stand to benefit from bioterrorism funding think that it is a threat is inaccurate. Many molecular biologists, including Craig Venter, understand what can be done with the new technologies and very concerned about what may happen in the near future as a result.

I know that you think a lot of bioterrorism money has been wasted. I agree with you about that. However, just because knuckleheads have wasted bioterrorism money doesn't mean that only knuckleheads think bioterrorism is a real threat.

Although we do not understand completely how nucleic acid sequences translate into transmission and lethality of viruses, it is not accurate to imply that we don't know anything. We know a lot and can make reasonable guesses which, thanks to the new technology, we can easily put into practice cheaply and quickly. These experimental viruses could be tested in animals to confirm hypotheses.

As regards blowback, this limits the range of potential bioweapons to one, imo: influenza. A weaponised H5N1 virus could easily be constructed that would be indistinguishable from the natural ones. The purpose would be depopulation of the earth in order to grab scarce resources.

I believe this strategy has already been discussed by the Chinese government. Anyone who thinks such an evil is to great to be considered needs to read some history.

I agree with Monotreme on this. I think, like many other biological scientists, you are whistling past the graveyard.

The capabilities are changing fast. You mention the idea that proliferation of biocontainment labs increases the risk that a nasty person will get hold of a dangerous agent. It might. But new abilities in synthesizing longish DNA bits are much, much more dangerous. Ebola is only what, 19 kb? A recipe for reconstituting the virus from the nucleotide sequence has been published (part of study looking at effects of site-directed mutagenesis of the original sequence).

You also imply that the anyone who wants to talk about what a small number of very bad people might do with a pathogen (engineered or not) are always bent on clamping down with secrecy. Not all of them are, and I've spoken with many who understand that won't work. Instead, they want to get the scientific community to think about what the possibilities are.

Please think about this one some more. It's not so easy to write off as mere scare mongering.

For revere or anyone else interested in learning more about gene synthesis, I recommend the following paper:

Gene synthesis demystified.
Czar MJ, Anderson JC, Bader JS, Peccoud J. Trends Biotechnol. 2009 Feb;27(2):63-72. Epub 2008 Dec 26
http://www.ncbi.nlm.nih.gov/pubmed/19111926

It has a section on bioterrorism.

Mono, Rob: You both raise serious issues which I should address. I'll likely to it in another post soon (I am currently taking part in a "strategic planning" exercise, complete with flip charts), and this takes some reflection. Thanks for the link. Will read with interest.

revere, glad you found the link useful. I'll look forward to your next post on this.

I am currently taking part in a "strategic planning" exercise, complete with flip charts

Didn't anyone tell you that you shouldn't use the phrase "flip charts", as it may be offensive to certain islanders of southeast Asian descent? You musta missed the requisite diversity training.My condolences on your attendance at such an adventure.

MoM,

Then, you need to look another "strategic planning" by ICA ( Institute of Cultural Affairs)http://www.lensinternational.com/lensinternational.html

full of participation, facilitation and motivation. It is indeed the program of life process. Look at it, at least one more time. :-).

Piggy-backing flu on smallpox vaccine

revere — Mon, 02 Mar 2009 06:33:56 +0000

Piggy-backing flu on smallpox vaccine

There is as yet no pandemic bird flu vaccine but there are a lot of potential vaccines. The recent fiasco involving Baxter International (here, here) involved one in development. There are many more. They employ old and new technologies and are in various stages, a few in early clinical trials. Many more are in the pre-clinical (animal or test tube) phase, although they are frequently reported in the news because the company developing it wants to attract support or publicity. I often don't pay attention to announcements of "breakthroughs" that are successful in mice. Many vaccines work in mice but not in humans or work in mice and can't be used in humans because of side effects. This weekend we are brought news of yet another of these. It was also announced at a press conference, but no company's name was connected with it, the paper is just published in a peer reviewed journal, and no financial conflicts or commercial research support is listed. The money comes from NIH and the team includes highly experienced and respected flu scientists. The news reports of the science were interesting enough I decided to invest a few hours in reading the paper, entitled "Vaccinia Virus-Based Multivalent H5N1 Avian Influenza Vaccines Adjuvanted with IL-15 Confer Sterile Cross-Clade Protection in Mice" (Poon et al., The Journal of Immunology, 2009, 182: 3063-3071 [subscription required]). Here's the description from Reuters:

Scientists in Hong Kong and the United States have developed an experimental H5N1 bird flu vaccine for people by piggy-backing it on the well-tested and highly successful smallpox vaccine.
Initial tests on mice showed the vaccine to be highly effective, they told a news conference in Hong Kong on Sunday.

[snip]

Smallpox was eradicated worldwide in 1979 and the experts are hoping that their novel H5N1 vaccine can ride on the various advantages of the smallpox vaccine.

The smallpox vaccine is very cheap, has a long shelf-life of several years and does not require highly sophisticated laboratories, making it easier for poorer countries to produce.

"It is very stable and you can pack them off to developing countries and use them. They require refrigeration but it is less critical than other vaccines," Peiris said.

"Smallpox production capacity has gone down but many countries have the technology and the expertise to do it, and if necessary, it can be very quickly scaled up."

"But for other strategies (of producing H5N1 vaccines), it is not possible to rapidly set up manufacturing plants all over the world as they require very specialised plants." (Tan Ee Lyn, Reuters)

This gives the gist, but as usual there is a bit more to it. Vaccinia virus is the virus of cowpox, a much less serious disease than smallpox. If you can be made immune to cowpox you will also be made immune to smallpox, something demonstrated by Edward Jenner in 1796. The word vaccination comes from the Latin word for cow (vacca), as in cowpox. When we are intentionally infected with vaccinia virus (via a scratch on our upper arms), the infected cells make copies of the virus and the proteins on the virus induce the immunity. For most people with healthy immune systems, vaccinia infection is mild and long lasting immunity to smallpox virus results. Because humans are the only reservoir for smallpox, it was possible to eradicate the disease by systematic vaccination campaigns. The last death from smallpox occurred in 1978. Ironically, it was a result of a laboratory accident, and more ironically, still occurred on September 11 of that year.

What the newly announced mouse vaccine did was insert into the vaccinia virus the genes for five proteins made by H5N1, the bird flu virus. These genes are the ones that make the hemagglutinin (H5), neuraminidase (N1) proteins, the matrix protein, M1, the ion-channel protein M2 and the nucleoprotein, NP. Most of these proteins, including H5, are not very immunogenic in humans, i.e., they don't produce strong antibody reactions, so additional materials, called adjuvants, are frequently added to vaccines to boost the immune response. A standard adjuvant is one made of an aluminum compound, but now there are others, some of them proprietary so we don't know much about them. These extra materials also increase the likelihood of side effects. The new vaccine used a different kind of adjuvant, a naturally produced immune system modulator called a cytokine. Along with the genes for the viral proteins they also inserted the gene for the human cytokine, interleukin-15 (IL-15). IL-15 stimulates various components of the immune system, so the idea was to use this innate biological mechanism as an adjuvant. On each of these genes a sequences used by the vaccinia virus to start and stop the production of proteins from genes was added and all of them lined up end to end and put into the vaccinia virus. Now when the virus infected the mouse cells, they produced not only vaccinia proteins but also the added proteins from the H5N1 and IL-15.

That's the basic idea, but there are a lot of i's to dot and t's to cross when you do science, and most of the 9 pages of this paper are taken up with those matters. For example, the research team made vaccinia vectors that had a the full-length IL-15 gene with a mutation that made inactive IL-15 so they could see what the effect of the adjuvant was. They also had a vaccinia virus with only IL-15 added, so they could see the effect of the viral proteins. They checked what was going on in many different ways. For example, they measured the level of certain antibodies to see what the vaccinia virus was producing and they checked to see if the antibodies being produced could react to more than the specific virus whose genes were used. The ability to react more broadly than specific strain could mean that they had a vaccine that could be used before a pandemic materialized. At the moment we have to wait for the pandemic to start because we can only make vaccines against very specific strains. They also challenged mice with H5N1 to see how well the vaccine protected them and how quickly the protection took hold.

Finally they tried the same tricks (although only using two of the viral proteins, HA and NA) with a replication-deficient vaccinia strain called MVA (Modified Vaccinia Virus Ankara). MVA replicates very poorly in mammalian cells, but still makes large amounts protein. It is therefore useful for people with HIV or other immune defects who might be endangered by a live virus vaccinia vaccine that replicated well in human cells. Generalized vaccinia is a life threatening disease. With tens of millions of HIV positive people, an MVA-based vaccine could still be used. Unfortunately, these viruses are still grown in eggs, a serious problem because there aren't enough eggs in normal times to make sufficient vaccine if a pandemic strikes and the virus itself could exacerbate the problem by wiping out poultry. Presumably this problem can be solved if the overall strategy is successful.

And if you are a mouse, you have cause for optimism. Viral challenges that were 100% lethal in unimmunized mice were 100% protective in immunized ones, whether or not IL-15 was involved. Moreover the antibody response was long lasting and appeared much sooner (9 days versus 28 days) compared to the only FDA approved vaccine now being stockpiled by the US government made by Sanofi-Aventis. The Sanofi vaccine is an inactivated (i.e., not live virus) detergent extracted vaccine with added chemical adjuvant. It's active ingredients are sub-fractions of viral proteins. In addition, the new vaccine's neutralizing antibody production held across several H5N1 variants, but not all.

This is a new kind of bird flu vaccine, but the science isn't new. Using vaccinia virus as a vector has been on the agenda for a long time and it has been accomplished frequently in the laboratory. That much I knew. But in a quick literature search I was surprised to find that protecting mice with replication-deficient MVA vectors for flu virus is also old, going back at least 15 years to a paper by Sutter et al. ("A recombinant vector derived from the host range-restricted and highly attenuated MVA strain of vaccinia virus stimulates protective immunity in mice to influenza virus,", Vaccine. 1994 Aug;12(11):1032-40; not cited in the Poon et al. paper).

This paper adds significantly to that work, however. Here's some of the authors' discussion on that point:

Our vaccine development strategy involved three elements, namely the selection of a live delivery vector, the incorporation of a repertoire of antigenic targets to achieve broad cross protection, and the incorporation of a molecular adjuvant to enhance the breadth and durability of vaccine-induced immune responses. In designing our multivalent H5N1 influenza vaccine candidates, we opted to use a live viral vector vaccinia virus for a number of reasons . . . Vaccinia virus has a proven record of efficacy and safety and carries the feasibility of large-scale manufacture in a relatively short time frame. Vaccinia recombinants are genetically stable and possess the intrinsic capacity to induce multiple arms of the immune system conferring robust and sustainable immune responses. Importantly, unlike in the case of Ad5-vectored vaccines [adenovirus vectors, another way to smuggle viral protein making genes into a live virus vaccine], pre-existing Abs [that is, pre-existing immunity to the viral vector itself] to vaccinia virus in the general population that could impede vaccine efficacy are likely to be less of a problem, because smallpox vaccinations ended in the early 1970s globally. In addition, vaccinia recombinants expressing individual influenza genes from various subtypes such as the hemagglutinin gene, nuclear protein gene, or matrix M1 gene have been shown to protect animals from a subsequent lethal challenge of virulent influenza viruses. We selected the replication-competent, FDA-licensed smallpox Dryvax vaccine (Wyeth strain) as the backbone for integrating H5N1 avian influenza viral genes, because >1 billion people have been vaccinated with the Dryvax vaccine during the smallpox eradication campaigns four to five decades ago and recently the FDA has approved its production in Vero cell substrates, thus enabling a rapid scale-up of Dryvax-based vaccine manufacturing (see U.S. Food and Drug Administration news report for September 1, 2007; www.fda.gov/bbs/topics/NEWS/2007/NEW01693.html). (Poon et al., J. of Immunology, subs. req'd, cites omitted)

What are some of the possible pitfalls? First, it is always the case that what works in mice doesn't work in humans. Second, the addition of IL-15, while improving the laboratory test measures, may also have unanticipated effects in humans. After all, turning the knob on an immune system control might easily do things that aren't so good. This vaccine also works without IL-15 adjuvant, but not as well. But if IL-15 is a problem, it still make work good enough. And while naturally immunity to vaccinia virus isn't present in people born after the 1970s, there are a lot of us older than that. Some of their results suggest that won't be a problem, but, again, we'll have to see.

Then there's the biggest wild card of all. This technology, even if highly effective (a big "if") won't be ready for widespead use for some years, probably at least three. Is the influenza virus going to be kind enough to wait around? As they say, "timing is everything."

revere Mon, 03/02/2009 - 01:33

Tags

bioengineering

biology

bird flu

Pandemic preparedness

vaccines

revere: just a couple of points of clarification. technically, at least as far as we know, baxter's fiasco didn't actually involve their h5n1 vaccine ("in development") but rather a live h5n1 virus. (i.e., the contamination is reported to be their vaccine.) also, the h5n1 vaccine stockpiled by the u.s. (sanofi's) isn't formulated with an "added chemical adjuvant," which is why dose-sparing is such an issue. (from fda: http://www.fda.gov/cber/label/h5n1san041707lb.pdf)

sorry if i misinterpreted what you said.

edit: meant to say "(i.e., the contamination is NOT reported to be FROM their vaccine.)" sorry for the confusion.

Vaccinia virus is the virus of cowpox

Just as a minor side note, because it's one of my pet peeves -- vaccinia is not the same virus as cowpox. The two are closely related but distinct poxviruses.

Cowpox was Jenner's original smallpox vaccine, but at some point in history cowpox was replaced by vaccinia virus. The true host of vaccinia is unknown.

brendan: Yes, that's why I said a vaccine in development. We don't know what the experimental virus material was.

iayork: Thanks for the clarification/correction. Appreciated.

revere: point taken, and i agree we don't know nearly enough about the baxter issue. however, tests proved that the h5n1 that killed the ferrets was a live virus. baxter's vaccine is whole but inactivated. whether the h3n2 component was baxter's attempt at a seasonal vaccine is a whole other (unknown) matter.

What are some of the possible pitfalls?

Also, it's only good once. If we pull the trigger on this approach for a threat we won't be able to use it again for a generation or so.

And while naturally immunity to vaccinia virus isn't present in people born after the 1970s, there are a lot of us older than that.

I had wondered about that. Do people who've been vaccinated against smallpox still have that immunity, or has it faded over time?

I thought D.C. Sessions had a good point, too. Perhaps an argument for holding off mass vaccination until a pandemic was on, at the very least; or at most, for developing a pan-flu (so to speak) vaccine.

pre-existing Abs [snip] to vaccinia virus in the general population that could impede vaccine efficacy are likely to be less of a problem, because smallpox vaccinations ended in the early 1970s globally.

Except, of course, for those Public Health and Emergency Response personnel who "volunteered" to be vaccinated after 9-11 to protect us from Saddam's Smallpox Initiative (SSI)

Would piggybacking the influenza vaccine off the smallpox vaccine mean that people who can't get the smallpox vaccine for medical reasons (eczema, for instance) couldn't take the influenza vaccine as well?

interro: Yes, that's right. But that's what the other construct through MVA was all about. (see para. that starts, "Finally . . . "). But you can't grow MVA in vero cells, only chicken eggs (the whole point is that they don't grow in mammalian cells), so they'd have to make a shithouse full of the stuff and then stockpile it for use in immunocompromised people.

Thanks, Revere. I sort of missed the import of that paragraph, because I was thinking more along the lines of eczema rather than HIV, having the former and not the latter...

According to the FDA:

"In studies, about 1 in 175 healthy adults who received smallpox vaccine for the first time developed inflammation and swelling of the heart or surrounding tissues (myocarditis and pericarditis)."

http://www.fda.gov/consumer/updates/smallpox090407.html

I'd like to see the data and the case definition(s) for myocarditis and pericarditis.

Bioengineered tissue transplant saves a life

revere — Thu, 20 Nov 2008 06:24:00 +0000

Bioengineered tissue transplant saves a life

There is a story on the wires today about an upcoming Lancet article describing the case of a young Columbian woman whose failing airway was replaced by a bioengineered airway whose cells were cultured from adult stem cells obtained from the patient's bone marrow. Since there is as yet no scientific paper, I got these details from a press release from the University of Bristol, one of four participating European universities in this unique case (the others were in Barcelona, Padua and Milan).

The 30 year old patient's main airway (the lower trachea) and left main stem bronchus (one of the two branches, to the right and left lungs) had been destroyed by TB and she was so short of breath she could no longer care for her children or perform normal activities of daily life. The technique was to use a cell free skeleton of the tracheal and bronchial segments (obtained from a Spanish donor who died of a stroke) and repopulate it with pluripotent stem cells obtained from the patient's bone marrow. The stem cells were then grown in the laboratory of Professor Martin Birchallat the University of Bristol and then matured into chondrocytes. This was a technique used to treat osteoarthritis in another laboratory. In osteoarthritis the cartilage of the joint surfaces is worn off and this was seen as a way to replace them. Use to grow an airway was a new application and in this case saved this young mother's life.

The donor trachea was first denuded of its cells so that there would be no foreign antigens to provoke a graft rejection. That took about 6 weeks. It was then seeded on the outside of the cartilage skeleton with the patient's newly grown chondrocytes, using a bioreactor developed at the Politecnico di Milano, Italy. The chondrocytes migrated into the interior of the cartilage skeleton which was seeded with epithelial cells under defined conditions to allow the development of each individual cell type. The result was a bioengineered traceal-bronchial graft containing the patient's cells. It was transplanted into the patient in June of this year.

It not only saved her life, it seems to have given her a normal life back again:

Professor Macchiarini, lead author on the paper, said: "We are terribly excited by these results. Just four days after transplantation the graft was almost indistinguishable from adjacent normal bronchi. After one month, a biopsy elicited local bleeding, indicating that the blood vessels had already grown back successfully".

[snip]

The patient, Claudia Castillo, a young woman from Colombia but now living in Spain, had no complications from the operation and was discharged from hospital on the tenth post-operative day. She has remained well since and has a normal quality of life. She is able to care for her children, walk up two flights of stairs and occasionally go out dancing in the evenings. (Eurekalert)

This is a rather remarkable case report. We are now in the era of bioengineered tissues. Exactly where this will lead us we don't know, but the field seems to be moving with remarkable rapidity. It again raises the idea that tissues might be made in laboratory flasks not only for medical uses but for food.

But that's another, and surprisingly controversial, subject (we've discussed it a couple of times and it always gets a very negative reaction).

revere Thu, 11/20/2008 - 01:24

Tags

bioengineering

This is a very exciting result to an ambitious operation, and it's no surprise that it was in all the newspapers here in the UK yesterday.

Over at Pro-Test we've taken a look at the pre-clinical work behind this study http://www.pro-test.org.uk/b2evo/index.php?blog=7&title=title_1&more=1&…

It's taken many years and a lot of work, but I'll bet that Ms.Castillo is pleased that the researchers kept at it.

One thing I do wonder is whether there is enough donated tissue available to make this procedure an option in many countries. It's notable that Spain operates a policy of presumed consent for organ donation, and while relatives of the deceased still have the final say it's created a culture where Spain has the highest level of organ donation in Europe. I tissue engineering is to be more widely used I suspect that synthetic scaffolds may by required.

Once the donor trachea was denuded of cells, did it matter whether the remaining scaffold was human in origin (aside from the presumably more natural shape)?

I assume it does matter, given references to Spain's policy on organ donation, but would a pig trachea have worked?

That's a good point. Implants made from non-human extracellular matrix have been used in other parts of the body (e.g. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W6V-4BP9MW3-…), but as the authors of the Lancet paper point out the respiratory tract does contain more active immune system cells than most other organs, so avoiding any immune response was vital. Their method described in the Lancet paper didn't completely remove all chondrocyte cells but appears to have removed most of the antigens that could trigger an immune response.

I think that it should be possible to use ECM from non-human species for this purpose, though the processes used to remove cells and antigens will probably need further improvement.

I must say, I was certainly taken aback by the comment that "We are now in the ear of bioengineered tissues." Were you saying that bioengineered tissues would form a gigantic ear that would envelop us? Perhaps this is some sort of metaphor unique to your linguistic group, similar to being "under the thumb" or "ground underfoot"? Or is this the dawn of bioenginearing?

Aw, jeez, it's just a typo. There went all my fun.

"I must say, I was certainly taken aback by the comment that "We are now in the ear of bioengineered tissues." Were you saying that bioengineered tissues would form a gigantic ear that would envelop us?"

Now that you mention the ear remember this http://www.abc.net.au/science/articles/2006/06/02/1644154.htm?site=scie…

If revere had read the University of Bristol's press release properly, they would have seen that there IS a paper about this study, published in the LANCET on Tuesday. Hence the press release.

Red flag on the flu vaccine front

revere — Mon, 06 Oct 2008 05:35:12 +0000

Red flag on the flu vaccine front

A story in CIDRAP News by the always excellent science journalist Maryn McKenna provides food for thought:.

A flu vaccine manufacturer's decision not to build a US facility has highlighted the perpetual mismatch between flu-shot supply and demand--and the reality that the mismatch may undermine plans for pandemic flu vaccines.
On Tuesday, Solvay Pharmaceuticals Inc. of Marietta, Ga., announced that it was canceling plans to build a US flu-vaccine manufacturing plant, a $386 million project that Birmingham, Ala., and Athens, Ga., have been competing for. The plant would have made both seasonal and pandemic flu vaccines--but at just about the moment when a final site selection was expected, the company announced that the economics of the two-year-old deal no longer make sense. (Maryn McKenna, CIDRAP News)

The US Government sunk almost $300 million into Solvay for design and development of the new plant but didn't provide enough for capitalizing it. Apparently to make economic sense some companies require that someone else pay all the upfront costs. I'm sure this is true for Solvay, a chemical, plastics and pharmaceutical conglomerate based in Belgium. Why invest a dollar (or a Euro) in flu vaccine, even though it will make you a tidy profit, when you can invest in some other product that can make you a big profit. That makes business sense. So the losers in this one are US taxpayers (so what else is new?). But the problem, as McKenna points out, is probably deeper than a bad investment of tax dollars:

Nevertheless, the Solvay decision deprives the United States of a domestic source for pandemic flu vaccine if or when a global outbreak begins. And by refusing to offer supply into an uncertain market, the company is challenging the central assumption behind US and global planning for pandemic-vaccine capacity: that demand for seasonal vaccine will provide companies with a rationale for making more vaccine than they now do.

Federal health officials have asserted many times that demand will boost manufacturing capacity to the level needed for a pandemic. To reach that level, the World Health Organization's 2006 "Global Pandemic Influenza Action Plan" calls for countries to boost their flu-shot usage to 75% of their populations, including countries where seasonal vaccine has never been used.

Here's how I would say this: the market doesn't work for flu vaccine. It is like saying that a war is like the market and will call up a demand for an army. so between wars we can disband the military. I might like that, but if you believe there are real threats out there requiring a military this would be nonsense to you. Since most scientists think there is a pandemic threat out there, why should we let "the market" govern if we have the resources if and when we need them? Because the US government, especially this administration but not only this administration, worships the market (except when they don't) and kowtows to drug companies (almost always).

If the market doesn't work for flu vaccine I see no reason to throw up our hands and give up. We construct another mechanism. In this case it could be a global network of regional vaccine laboratories (maybe ten or a dozen, with some large regions, like the US, having several) that have adequate reserve capacity to ramp up production quickly in the case of need. In the absence of demand this produces unused and redundant capacity and is inefficient. As do standing armies in times of peace. The cost would be borne by the global community as a whole.

The alternative is to do as we are dong now, leave it to the private sector which has no incentive to meet the need, and should a pandemic arise will be able to respond too little, too late and at great cost, both because the demand will exceed supply and the loss in pain in suffering from the missed opportunity will be enormous.

The Solvay decision is another warning flag. Of course, we have shown a prodigious capacity to ignore warning flags

revere Mon, 10/06/2008 - 01:35

Tags

bioengineering

bird flu

vaccines

Great analogy to war... it's about time we had a war on something important where we could have an effect.
You are describing yet another market failure. The crony capitalists like to tout the benefits of the free market when it means subsidies and protections for them (not really a free market) but don't admit to the problem of market failure.
The US health care system is a case study in market failure with the sole exception of the socialist Medicare program (in an irony hopelessly beyond Palins ability to comprehend, this is what he was referring to when he warned that without vigilance, "you and I are going to spend our sunset years...").

I have been argueing the case that pandemic vaccine production should be treated, and funded, as a matter of national security I am not even going to try and re-write it again now. The text below is just a straight cut'n'paste from an earlier post.

It may be useful to split the vaccine problem in two - seasonal & pandemic. Seasonal vaccine has been supporting itself - commercially - so far and while the major players have been in no great hurry to pay for certification of a new (not egg based) manufacturing process cell based production is here. Pandemic vaccine needs much the same end product but the timings are a little different. Seasonal flu vaccines manufacturing capacity survives on regular alternating orders from the north and south hemisphere. These orders are placed 6 months in advance and are predictable in size and timing. If you want to supply the pandemic trade you will need capacity to produce a billion odd doses at a few weeks notice and you may only get an order every 30 or 40 years. This is understandably not the kind of business plan that is going to draw investors. If you build a plant to meet this surge the chances are it will be obsolete before it is needed, also egg based production is a non starter as it can not deliver given the short time between pandemic onset and peak infection period.
Either we just accept these things happen and accept the odd culling of mankind or we devise a plan to cope with these periodic attacks on humanity. If we conclude that a massive investment to mitigate the effects of a severe flu pandemic are worth paying for - not a no brainer as there are plenty of other problems that could benefit from this level of global commitment - then I would argue that this is a national security issue and should be treated - and funded - as such. While advocating a major effort in pandemic planning what I am implicitly planning for is not any old flu pandemic (1957 / 1968) but a 1918+ pandemic, the distinction is important. In a 1918+ pandemic you can not devise a xenophobic plan, protecting you citizens alone does not solve the problem as the collateral damage to the worlds economy would leave them healthy but wishing this recession was mild like the 1930's. Enlightened self interest means the richer nations need to pay for and implement a plan that covers most of the worlds people regardless of the fact they can not pay themselves - this is the price we pay for being relatively comfortably off and wanting to stay that way.

Re-reading the above I am not sure I made one key point very clearly. The seasonal vaccine program is a hindrance to the development of a pandemic vaccine program.

The options, as I see them, are

Pay the Pharmaceutical industry to switch to a cell - or monoclonal antibody - based system and maintain pandemic surge capacity.

Pay for the upgrading of the veterinary vaccine capacity as above and maintain it as dual use so it can be switched to human production in a pandemic.

Any other suggestions?

The military apparently already takes care of its own with an influenza vaccine program.
http://www.vaccines.mil/Default.aspx
"All military members are required to be vaccinated against the flu each year."

I don't know, but I imagine soldiers are being immunized in their home bases -- so the manufacture, distribution, and the rest of the facilities already exist to immunize the military, and could, with some careful planning, likely be scaled up to cover the rest of the population in the event of a pandemic flu.

Australia has been so far ahead of the curveball on prepandemic vaccine research eg. new adjuvants and delivery modes, it feels almost...Prescient!?!

Indeed crf, I myself became a tad worried back in 1997, watching an Oz SBS television newsreport on human H5N1 fatalities in Hong Kong (my lover from that time is Chinese-Australian, whose family hails from that region of China).

Unfortunately, like a "prescient" child yet to physically "join all the dots to form a coherent picture", I began blabbin' on 'bout an "impending global disaster" minus the physical proof.

Tsk, the West Australian medicolegal homophobes saw a "tasty meal" in me and gorged themselves... The criminal violence vomitted at me has left me utterly contemptuous of all West Australian government agencies -- as bored spoitbrat tossers (of all ages) working in state government jobs take psychosexual pleasure enacting the "Orwellian infantalization process" of 1984.

But crf, I digress... Yes, a former US-military mate of mine (Randy Kruger) has posted on EM many times complaining he had no choice but to take whatever vaccines the military command threw at serving members. So yeah crf, the US production capacity IS there...

The only thang the American public needs now is highly EFFICIENT prepandemic vaccine adjuvants and delivery modes... And who has that!?! The arrogant Aussies, of course!

@ ScienceDirect -- "The utility of ISCOMATRIX adjuvant for dose reduction of antigen for vaccines requiring antibody responses" Vaccine 30 March 2007

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TD4-4MP5JHR-…

Excerpt: "The capacity of an adjuvant to reduce the amount of antigen required in vaccines would be beneficial in a variety of settings, including situations where antigen is difficult or expensive to manufacture, or in situations where demand exceeds production capacity, such as pandemic influenza. The ability to reduce antigen dose would also be a significant advantage in combination vaccines, and vaccines that by necessity must contain multiple antigens to accommodate variability between strains or genotypes... Therefore, ISCOMATRIX adjuvant has the potential to substantially reduce the dose of antigen required in human vaccines, without compromising the immune response."

Again @ Nature.com -- "Pulmonary delivery of ISCOMATRIX influenza vaccine induces both systemic and mucosal immunity with antigen dose sparing" Mucosal Immunology advance online publication 24 September 2008
www.nature.com/mi/journal/vaop/ncurrent/abs/mi200859a.html