April 2005 Archives

Another biological chassis and power supply

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If you want to build new widgets using biology, you need to work with cells amenable to the task.   Tom Knight, at MIT, prefers the innocuous insect commensal bacterium Mesoplasma florum as a prototype biological chassis and power supply for genetic circuits.

After reading my article on garage biology in this month's Wired, David Metzgar, at the Naval Health Research Center, sent me a paper describing another candidate organism, Acinetobacter ADP1.  The paper describes ADP1 as naturally competent for genetic transformation and that it has a "strong natural tendency towards homology-directed recombination."  That is, it likes to harvest DNA from its environment and incorporate it into its genome.  Metzgar writes that, "The close relationship between E. coli and ADP1, combined with the newly available whole genome sequence of ADP1, allows the tremendous amount of existing knowledge related to gene function and metabolism of E. coli to be applied directly to ADP1."  They ported a variety of genes directly from coli to ADP1 without modification.

Since it is common, easily grown, and poses no pathogenic threat to humans, this could be a useful bug.

Acquiring Open Source Projects

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One of the issues that always arises in discussions of Open Source Biology is how anyone will make any money.  Not everyone is interested in money, of course, but molecular biology is still a bit expensive and requires capital of some sort to keep it running.  Without the possibility of a return on their investment, most investors probably won't go near open source biology.

This was an explicit objection raised by a banker/VC type at After the Genome VI, in December of 2000.  I've heard similar complaints all along the way, though the VC in question also added something like "they won't let you do it" to his oration, presumably refering to big biotech companies.  I immediately asked myself what "they" could do about it, and have pondered the question ever since.  The problem doesn't seem to be encouraging tinkerers to have at it, or that big companies might prevent them from doing so, but rather turning the fruits of tinkering into useful tools and products that most people want to use.

Products take a long time to develop to the stage where people want to actually purchase them.  Lot's of open source software in particular doesn't attract a large user base because the interface isn't as polished as that provided by commercial houses, even if the guts of the code are better.  This is as true of software and cars as it is of molecules and other biological technology.  In my experience, most biologists seem to want a box with an instruction book -- a package they can use to produce data -- and are rather less likely to put up with sorting out the intricasies of working with a tube full of molecules from some guy down the street.

On the one hand tools and skills are proliferating at a remarkable rate, democratising the technology and its applications, but on the other most new useful tools still come from "traditionally" funded and run corporations, and we want to ensure continued investment that funds that development of finished products.

One way out of this might be the aquisition of open source projects by established companies, or by start-ups funded specifically to take a project private and push the commercial applications.  It turns out this has now happened in the open source software world.  This obviously can only work if all the contributors to the open source project agree to sell their rights as developers to the company.

David Berlind describes what transpired, and explores its implications, at ZDnet:

To acquire an open source project, the acquirer must be absolutely certain that they are acquiring the copyrights to all of the code being used in the project.  Those copyrights ultimately belong to the individual contributors to the project who, up until the point of acquisition, would have been bequeathing certain rights to their code to others under whatever open source license is behind the project.  To the extent that licensing that code under an OSI-approved license is what let the code out out of the box and into the open source wild, there’s nothing that the acquirer can do to put it back in the box.  That code will always remain available under whatever open source license it was published.  But, by acquiring the copyrights and any trademarks associated with that code, the acquirer also acquires the right to modify and distribute the original code without having to make those modifications available under an open source license.  In other words, future versions of the open source software could become closed source.

The last sentence is perhaps the most interesting, particularly in the context of biology.  I can imagine open source biological technologies developed in a distributed way, or at least developed by more than one person, which are useful to those willing to master the eccentricities but which are not widely used because they may be unwieldly.  In steps a commercial endeavor to tie up all the loose ends, and then put it in a nice package with a bow on top -- complete with instruction manual, please.  As with software projects, all the details disclosed prior to aquisition would remain in the public domain, but any further work the company put into development would remain their property and contribute to the value of the final product.

This is, of course, similar to how technology is moved from universities into the private sector.  So it isn't a great stretch of the imagination to see that it might work with distributed, "amateur" development efforts.  Something to consider.

Heinz Feldmann on Marburg

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Heinz Feldmann, head of the Level 4 labs at the National Microbiology Laboratory of the Public Health Agency of Canada, was in town this week to give a couple of talks on the Marburg virus.  He just returned from field work in Uige, the center of the current outbreak.

Here are a few notes:

  • There are claims that up to 80% of the highland Gorillas in the area have been felled by Ebola, but Feldmann expressed some skepticism and noted that none of the cases had been lab confirmed.  Evidently, there is  discussion of using experimental vaccines in the Gorillas to try to preserve the population.  This is more than can be done for the humans, because the vaccines have yet to undergo even safety testing.
  • Feldmann and others are working on vaccines for Marburg and Ebola, and adenovirus vectors don't work very well due to extensive seroprevalence in the population of neutralizing antibodies.
  • However, his lab is using VSV as a vector and this is working extremely well in monkeys.  When the GP protein from Marburg is included in VSV Virus Like Particles (VLPs), 100% of monkeys survive exposure with cross strain protection, including the "POP" strain thought to have been weaponized by the Soviets.  Ebola is a slightly different story, with 100% protection for any given strain, slightly less protection across strains, and zero cross species protection.

I am increasingly interested in the possibility of VLPs as the foundation of a synthetic and distributed vaccine production infrastructure.  Ralph Baric was in town a few weeks ago, and he said he was having success with VLP vaccines for Noroviruses.  So your next ocean cruise could well be diarrhea free.

It's a Flat World

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UPDATE (19 April, 05):  I completely forgot to link this entry to my previous post, Geographical Distribution of Biological Technologies, in which I comment on William Hoffman's World Stem Cell Policy Map.  Biological technologies are spread all over the planet already, and our current economic and technological lead (if we are still in the lead) cannot be maintained without siginificantly more investment and hard work.

------

I don't always agree with Thomas Friedman.  Current affairs a la Friedman often seem to me oversimplified.  But in the last week or so he has a couple of very nice pieces about the economic status of the United States.

In "Bush Disarms, Unilaterally" (15 April, 05) he argues that the Bush administration is heading in the wrong direction with its policies on investment in science, education, and economic development.  To wit;

One of the things that I can't figure out about the Bush team is why an administration that is so focused on projecting U.S. military strength abroad has taken such little interest in America's economic competitiveness at home - the underlying engine of our strength.

...We have a Treasury secretary from the railroad industry. We have an administration that won't lift a finger to prevent the expensing of stock options, which is going to inhibit the ability of U.S. high-tech firms to attract talent - at a time when China encourages its start-ups to grant stock options to young innovators. And we have movie theaters in certain U.S. towns afraid to show science films because they are based on evolution and not creationism.

The Bush team is proposing cutting the Pentagon's budget for basic science and technology research by 20 percent next year - after President Bush and the Republican Congress already slashed the 2005 budget of the National Science Foundation by $100 million.

When the National Innovation Initiative, a bipartisan study by the country's leading technologists and industrialists about how to re-energize U.S. competitiveness, was unveiled last December, it was virtually ignored by the White House. Did you hear about it? Probably not, because the president preferred to focus all attention on privatizing Social Security.

... Economics is not like war. It can be win-win. But you need to be at a certain level to be able to claim your share of a global pie that is both expanding and becoming more complex. Tax cuts can't solve every problem. This administration - which often seems more interested in indulging creationism than spurring creativity - is doing a very poor job of preparing the country for that next level.

In the Times Magazine a week ago Sunday, he made a broader argument about the state of global economic and technological competition in, "It's a Flat World, After All".  He writes;

In 1492 Christopher Columbus set sail for India, going west. He had the Nina, the Pinta and the Santa Maria. He never did find India, but he called the people he met ''Indians'' and came home and reported to his king and queen: ''The world is round.'' I set off for India 512 years later. I knew just which direction I was going. I went east. I had Lufthansa business class, and I came home and reported only to my wife and only in a whisper: ''The world is flat.''

And therein lies a tale of technology and geoeconomics that is fundamentally reshaping our lives -- much, much more quickly than many people realize. It all happened while we were sleeping, or rather while we were focused on 9/11, the dot-com bust and Enron -- which even prompted some to wonder whether globalization was over. Actually, just the opposite was true, which is why it's time to wake up and prepare ourselves for this flat world, because others already are, and there is no time to waste.

...Here I was in Bangalore -- more than 500 years after Columbus sailed over the horizon, looking for a shorter route to India using the rudimentary navigational technologies of his day, and returned safely to prove definitively that the world was round -- and one of India's smartest engineers, trained at his country's top technical institute and backed by the most modern technologies of his day, was telling me that the world was flat, as flat as that screen on which he can host a meeting of his whole global supply chain. Even more interesting, he was citing this development as a new milestone in human progress and a great opportunity for India and the world -- the fact that we had made our world flat!

...When the world is flat, you can innovate without having to emigrate. This is going to get interesting. We are about to see creative destruction on steroids.

...We need to get going immediately. It takes 15 years to train a good engineer, because, ladies and gentlemen, this really is rocket science. So parents, throw away the Game Boy, turn off the television and get your kids to work. There is no sugar-coating this: in a flat world, every individual is going to have to run a little faster if he or she wants to advance his or her standard of living. When I was growing up, my parents used to say to me, ''Tom, finish your dinner -- people in China are starving.'' But after sailing to the edges of the flat world for a year, I am now telling my own daughters, ''Girls, finish your homework -- people in China and India are starving for your jobs.'' I repeat, this is not a test. This is the beginning of a crisis that won't remain quiet for long. And as the Stanford economist Paul Romer so rightly says, ''A crisis is a terrible thing to waste.'' 

Indeed.  China and India aren't waiting around for people in the US to lay the groundwork for the next generation of technologies, whether new materials, new software, or biological technologies.  They have economic power, huge and highly educated populations, and a motivation to innovate themselves into the first world.  From my experience in both industry and academia, it looks to me like we are already at least a decade behind in our investments in education and R&D.

East Bay Express Article on Open Source Biology

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Here is Nathanael Johnson's East Bay Express article on the origins of Open Source Biology.  I don't know if we deserve as much credit as Mr. Johnson gives us.  But I do miss hanging out at the Palace...

UPDATE (18 April 05):  Here are the original Intentional Biology and Open Source Biology web pages, which haven't been edited since 2000 or so.  Content by myself and Drew Endy.  This material is basically ancient history at this point, but not so bad for following the development of the ideas.

Marburg in Angola

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I'm catching up on the news, and trying to sort out what to make of the Marburg virus outbreak in Angola.

The 11 April, 2005 New York Times story reports;

The race to contain the outbreak of Marburg, a deadly relative of the better-known Ebola virus, is centered here in the town of Uíge (pronounced weezh), where health officials fear the makings of a public health disaster that could spread elsewhere in Angola and beyond.

The number of victims is already the largest ever recorded from a Marburg outbreak, and there is no effective treatment. Nine out of 10 people who get the virus die, usually within a week.

...The virus is named for the town in Germany where it was first identified in 1967 after laboratory workers were infected by monkeys from Uganda.

Scientists do not know the source of the virus or how this outbreak began. But the Centers for Disease Control and Prevention in Atlanta confirmed the first Marburg case in Uíge on March 8. That suggests that two months more of illness and deaths lie ahead.

It's a nasty bug, no question about it.

The 10 April, 2005 New York Times story by Sharon Lafraniere, "To Contain Virus in Angola, Group Wants Hospital Closed", contains other interesting tidbits.  The article begins;

UIGE, Angola, April 9 - An international medical charity battling a hemorrhagic fever that so far has killed 181 Angolans has urged the government to close the regional hospital here, at the center of the outbreak, saying the medical center itself is a source of the deadly infection.

Doctors Without Borders, the global relief organization that runs an isolation ward at the hospital for victims of the deadly fever, Marburg virus, told Angolan officials on Friday that the hospital should be closed if the rapidly spreading epidemic was to be contained.

Two other hospitals within 60 miles of Uige may also have to be shut down, said Monica de Castellarnau, the organization's emergency coordinator in Uige, the provincial capital, where the outbreak was first reported.

That possibility raises the prospect of a second health care crisis, one in which hundreds of thousands of people already facing a disease that is almost always fatal may suddenly have no access to hospital care. But in an interview in the streets of Uige, where an intensive effort is under way to find and isolate new cases of the virus, Ms. Castellarnau said there might be no alternative.

"The hospital has been the main source of infection," she said. "We have to break that chain somehow. It is a massive public health decision, and it must be taken by the government."

No doubt this ought to make people think hard about contingencies in an Avian Flu pandemic.  If we have to start implementing quarantines on hospitals and clinics because they are concentrated sources of virus, what happens to ongoing medical and emergency care?  Hopefully, the folks at Effect Measure are pondering this.

I also have, sitting on my desk, a preprint describing how both Ebola and Marburg employ mechanisms that suppress the human anti-viral response.  Since the article is not published, I can't describe the details here.  Essentially, both viruses specifically down-regulate key genes known to play a role in anti-viral reactions, down-regulate coagulation related gene expression, and also appear to suppress the ability of liver cells to regenerate clotting factors.

Reuters and the AP are both carrying stories about how local customs have led to the spread of the disease from corpses to family members, and about how hard it is to change those cultural practices.  The Marburg Wiki has similar information.

The AP story ends with the following tidbit, which is both interesting and troubling;

Angola's protracted civil war, which ended in 2002, wrecked the country's public infrastructure, including hospitals and roads.

Uige still bears the scars of that war: some houses are still partial ruins with bullet holes and smashed walls. When the outbreak began, the hospital didn't have a single pair of medical gloves, officials said.

Once again, this reminds us how carefully we have to watch the Avian Flu outbreak in SE Asia, particularly in the areas hit by the tsunami (see my post, A Confluence of Concerns).

Environmental Heresies

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Stewart Brand has an article, "Environmental Heresies", in the May, 2005 Technology Review, suggesting ways the environmental movement needs to adapt to changing demographics and technology.  I liked this piece so much I had to drop Mr. Brand a note to tell him so, along with a few questions.  I like what he responded with so much I asked if I could post it here.

At 2:47 PM -0700 4/14/2005, Rob Carlson wrote:

Dear Stewart,

Well done on the Tech Review piece.  I like and agree with most of what you said, though I am still on the fence about nuclear power.  Disposing the waste is the sticking point for me.  So is the tendency to offload the real costs onto the back end, which corporate interests tend to escape.  Everything near the reaction becomes deadly radioactive, so the fuel isn't the only problem.  The volume and the mass are not small.  I think the long term solution to this is the space elevator, but that is another conversation.

I do have a question about one of your points, however.  I appreciate the observations concerning urbanization, though my drives through California's Central Valley come to mind.  As you know, farmland, some of which is fallow, is being sacrificed for housing.  Wetlands are under threat all over the place.  This is the sort of sprawl we are fighting in the NW, too.  How densely can we convince people to live?  Sarah and I made the conscious choice to buy a small townhouse within walking distance of work, grocery stores, a kayak launching point (which I walk my boats to on a small cart), etc.  But I am not sure how many other people will choose to live like this.

Perhaps my scale is completely out of whack, as my lifestyle is much closer to the Central Valley McMansion than to that lived by all but the most wealthy in central and east Asia.  I suppose the question is how density in American cities is changing as a function of distance from the urban core.  That is, are people actually moving to the core, or are the tails of the distribution just reaching further away as people move to the burbs?  What do the figures look like for big Asian cities?  And are all those increasing numbers of city dwellers as well off as the generally well-educated Indian women, or are there just a lot more urban poor -- those billion urban squatters?  Is the number density of rural populations decreasing, or are we just getting a whole hell of a lot more people being born and living their lives in the cities?

More questions than answers, as usual.  Once I get going, it's hard to stop.

- Rob

Here is what Stewart responded with:

There's a fair amount in this summary of a talk I gave last week in San Francisco to the Long Now crowd.  Two books:  THE CHALLENGE OF SLUMS (from the UN), and SHADOW CITIES, by Robert Neuwirth.

##

I started with a spectacular video of a stadium in Philadelphia being blown up last year.  The announcer on the video ends it, "Ladies and gentlemen, you have just witnessed history!"  Indeed demolition is the history of cities.

Cities are humanity's longest-lived organizations (Jericho dates back 10,500 years), but also the most constantly changing.  Even in Europe they consume 2-3% of their material fabric a year, which means a wholly new city every 50 years.  In the US and the developing world it's much faster.

Every week in the world a million new people move to cities.  In 2007 50% of our 6.5 billion population will live in cities.  In 1800 it was 3% of the total population then.  In 1900 it was 14%.  In 2030 it's expected to be 61%.  This is a tipping point.  We're becoming a city planet.

One of the effects of globalization is to empower cities more and more.  Communications and economic activities bypass national boundaries.  With many national governments in the developing world discredited, corporations and NGOs go direct to where the markets, the workers, and the needs are, in the cities.  Every city is becoming a "world city."  Many elites don't live in one city now, they live "in cities."

Massive urbanization is stopping the population explosion cold.  When people move to town, their birthrate drops immediately to the replacement level of 2.1 children/woman, and keeps right on dropping.  Whereas children are an asset in the countryside, they're a liability in the city.  The remaining 2 billion people expected before world population peaks and begins dropping will all be urban dwellers (rural population is sinking everywhere).  And urban dwellers have fewer children.  Also more and more of the remaining population will be older people, who also don't have children.

I conjured some with a diagram showing a pace-layered cross section of civilization, whose components operate at importantly different rates.  Fashion changes quickly, Commerce less quickly, Infrastructure slower than that, then Governance, then Culture, and slowest is Nature.  The fast parts learn, propose, and absorb  shocks; the slow parts remember, integrate, and constrain.  The fast parts get all the attention.  The slow parts have all the power.

I found the same diagram applies to cities.  Indeed, as historians have pointed out, "Civilization is what happens in cities."  The robustness of pace layering is how cities learn.  Because cities particularly emphasize the faster elements, that is how they "teach" society at large.

Speed of urban development is not necessarily bad.  Many people deplored the huge Levittown tracts when they were created in the '40s and '50s, but they turned out to be tremendously adaptive and quickly adopted a local identity, with every house becoming different.  The form of housing that resists local identity is gated communities, with their fierce regulations prohibiting anything interesting being done by home owners that might affect real estate value for the neighbors (no laundry drying outside!).  If you want a new community to express local life and have deep adaptivity, emphasize the houses becoming homes rather than speculative real estate.

Vast new urban communities is the main event in the world for the present and coming decades.  The villages and countrysides of the entire world are emptying out.  Why?  I was told by Kavita Ramdas, head of the Global Fund for Women, "In the village, all there is for a woman is to obey her husband and family elder, pound grain, and sing.  If she moves to town, she can get a job, start a business, and get education for her children.  Her independence goes up, and her religious fundamentalism goes down."

So much for the romanticism of villages.  In reality, life in the country is dull, backbreaking, impoverished, restricted, exposed, and dangerous.  Life in the city is exciting, less grueling, better paid, free, private, and safe.

One-sixth of humanity, a billion people, now live in squatter cities ("slums") and millions more are on the way.  Governments try everything to head them off, with total failure.  Squatter cities are vibrant places.  They're self-organized and self-constructed.  Newcomers find whole support communities of family, neighbors, and highly active religious groups (Pentacostal Christians and Islamicists).  The informal economy of the squatter cities is often larger than the formal economy.  Slum-laden Mumbai (Bombay) provides one-sixth of India's entire Gross Domestic Product.  The "agglomeration economies" of the burgeoning mega-cities leads to the highest wages, and that's what draws ever more people.

So besides solving the population problem, the growing cities are curing poverty.  What looks like huge cesspools of poverty in the slums are actually populations of people getting out of poverty as fast as they can.  And cities also have an environmental dimension which has not yet been well explored or developed.

There has been some useful analysis of the "ecological footprint" that cities make on the landscape, incorporating the impacts of fuel use, waste, etc. but that analysis has not compared the per-person impact of city dwellers versus that of people in the countryside, who drive longer distances, use large quantities of material, etc.  The effect of 1,000 people leaving a county of 1,000 people is much greater than that of the same 1,000 people showing up in a city of one million.  Density of occupation in cities has many environmental advantages yet to be examined.

At present there's little awareness among environmentalists that growing cities are where the action and opportunities are, and there's little scientific data being collected.  I think a large-scale, long-term environmental strategy for urbanization is needed, two-pronged.  One, take advantage of the emptying countryside (where the trees and other natural systems are growing back fast) and preserve, protect, and restore those landscape in a way that will retain their health when people eventually move back.  Two, bear down on helping the growing cities to become more humane to live in and better related to the natural systems around them.  Don't fight the squatters.  Join them.

###

Next month, Friday, May 13, Will Jarvis, author of TIME CAPSULES: A Cultural History, will speak on "Time Capsule Behavior."  There will be more about the vibrancy of squatter cities on Friday, June 10, with Robert Neuwirth, author of SHADOW CITIES, talking about "The 21st-century Medieval City."  Jared Diamond, author of COLLAPSE, will speak on a Friday this summer still being determined.

--Stewart Brand

I still wonder whether that increase in the urban population is from people "moving to cities", or whether they are being born there.  I guess I have some reading to do.

Here is the link to the Long Now Foundation Seminars.

Technology transfer to middle school students

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The upcoming 86th ANNUAL MEETING of the AAAS Pacific Division will be in Ashland, OR, June 12-16, 2005.  There will be a couple of workshops put on by Bio-Rad to help teachers understand how to use various kits within the classroom.  From the looks of it, some fairly sophisticated technology is now being introduced to students as early as middle school.  No genetic modification, but the workshops cover tools everyone uses in the lab to understand the systems they are working on, or systems they are building.

From the Meeting Schedule:

Bio-Rad Corporation of Hercules, CA, is presenting the following five hands-on workshops to give middle school, high school and university instructors the opportunity to try out some of the molecular biology kits they offer to educators. There is no charge for these workshops. However, participants must be registered for the meeting. Be sure to wear your meeting badge to each session. Space is on an “as available ” basis and preregistration is not required. Bio-Rad representatives will provide certificates of attendance for those desiring to utilize these workshops for professional development credits.

Wednesday, June 15

8:30 a.m.Genes in a Bottle. Extract and bottle your own DNA. Introduce your students to molecular biology with their own DNA! In this activity, you will extract and bottle the DNA from your own cheek cells to make a necklace. This real-world laboratory procedure is used to extract DNA from many different organisms for a variety of applications and integrates multiple life science standards in a single lesson. Seeing DNA makes it real. Be the first at your school to wear your DNA!

10:30 a.m. ELISA Immuno Explorer. Biology's magic bullet. Explore immunology with this topical, new hands-on classroom lab.ELISA (enzyme-linked immunosorbent assay) is a powerful antibody-based test used to detect diseases such as HIV/AIDS and SARS, and to trace pathogenic agents in water, food, and the air whether these emerge naturally or through acts of aggression. You will simulate the spreading of a disease, perform ELISA, and learn how this assay is used to identify and track agents of disease , or to detect molecular markers of cancer, pregnancy, and drug use. This kit integrates multiple standards in a single lesson, including antigen-antibody interactions and the role antibodies play in medicine, epidemiology, and biotechnology.

1:30 p.m. PV92 PCR. What pair of genes are you wearing? PCR is central to forensic science and many medical, archaeological, and ecological procedures. You will extract DNA from your own hair samples, then amplify and fingerprint a pair of alleles, an Alu repeat within PV92, a real forensic marker. This activity integrates multiple life science standards in a single lesson and covers a range of core content areas, from DNA replication to evolution to Hardy-Weinberg equilibrium theory.

Thursday, June 16

9:00 a.m. GMO Investigator/Analysis. Have your favorite foods been genetically modified (GM)? Currently, genetically modified organisms (GMOs) in foods do not have to be labeled in the US. Regardless of where you stand in the GM debate, wouldn't it be fun to know if the corn or soy-based foods you eat are GMO foods? This kit uses DNA extraction techniques, PCR, and gel electrophoresis to test common grocery store food products for the presence of GMO foods. This activity integrates and reinforces multiple life science standards in a single lesson.

1:00 p.m. Protein Fingerprinting. Can molecular evidence support evolution? DNA gets a lot of attention but proteins do all the work. Proteins give organisms their form and function and are the raw material for evolution because natural selection acts on phenotypes. Over time, accumulated changes in DNA (genotypes) lead to variation and ultimately, speciation. You will extract muscle proteins from both closely and distantly related species of fish and use protein electrophoresis to generate protein fingerprints to look for variations. This activity integrates multiple life science education standards in a single lesson from physiology to the theory of evolution to exploring the molecular framework of biology. DNA>RNA>Protein>Trait.

1957 Flu Redux (...almost...)

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The AP carried a story today that announced a recomendation (order?) from the WHO to destroy shipments of flu strains sent to labs around the world as part of an ongoing testing program.

The problem, it seems, is that the test kit contained the 1957 pandemic flu strain, which no one has been vaccinated against since 1968.  The story reports that, "It was not immediately clear why the 1957 pandemic strain, which killed between 1 million and 4 million people -- was in the proficiency test kits routinely sent to labs."  The story continues;

Most of the samples were sent starting last year at the request of the College of American Pathologists, which helps labs do proficiency testing. The last shipments were sent out in February.

Dr. Jared Schwartz, an official with the pathology college, said a private company, Meridian Bioscience Inc. of Cincinnati, Ohio, is paid to prepare the samples. The firm was told to pick an influenza A sample and chose from its stockpile the deadly 1957 H2N2 strain.

Regardless of the wisdom of this choice, it is interesting that it was caught at all -- one of the labs correctly identified the 1957 strain.  That bodes well for infectious disease surveillance, but note that this was a test kit sent to the labs, not an environmental sample that they had to test completely blind.

Note also that the strain is now out in the world again, and could thus be kept as a potential weapon.  Most of the kits were shipped to labs in the US, and the College of American Pathologists has requested confirmation in writing that all the test kits have been incinerated.  Which is great.  Except that the bug is still now out in the world.  Even if this was an accident -- especially if this was an accident -- the incident highlights how ill prepared the global community is for biological surprises.

UPDATE (14 April 05): Effect Measure has nice coverage of this incident.

Space Elevator Conference Update

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Here are Blaise Gassend's notes from Space Exploration 2005 about progress towards building the Space Elevator.  Also a Slashdot thread, full of the typical penetrating discourse.

It's the end of the world as we know it!

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The editorial in Science last week (8 April '05), "Twilight for the Enlightenment" (subscription required), laments the challenge to our "confidence in science and in rational methods of thought" by a trend for "some school boards [to] eliminate the teaching of evolution or require that religious versions of creation be represented as 'scientific' alternatives".  Donald Kennedy, the Editor in Chief, is also perturbed that, "In several school districts, geology materials are being rewritten because their dates for Earth's age are inconsistent with scripture (too old)."  This challenge obviously comes from the right.

Interestingly, there is a commentary in last week's Nature by Dick Taverne, a member of the UK House of Lords, entitled, "The new fundamentalism" (again, subscription required).  Lord(?) Taverne (never thought I would type that particular appellation) is concerned about, "The growing influence of 'green' activists who approach environmental issues with a semi-religious zeal and seemingly little regard for evidence".  Taverne suggests that these viewpoints, "Imperil not only the future of the biotech enterprise but also the health of society as a whole".  Thus science is getting it from the left, too.

So it seems the problem is a bit more general than "evangelical Christianity" pushing to smudge the boundary between church and state (Kennedy), or Greens engaging in "scaremongering" that might "allow new technology to be summarily dismissed on the basis of unsubstantiated claims...technologies on which our future health and wealth depends" (Taverne).  Across a broad swath of the political and social landscape, from the right and the left, there is a fundamental turn away from the mindset that has brought us profound increases in our standard of living and profound decreases in human suffering.  Though we have lots of work to do on both points on a global scale, we aren't going to get there by turning away from the Enlightenment.

Then again, perhaps it is just our turn to watch the empire pass.  India, China, Islam in the middle ages; these cultures all had their day in the sun and made choices that let the mantle pass to others.  But with the passion for science and technology throughout Central and East Asia, coupled with education and an excellent work ethic, the wheel may be coming back around.  At least progress will happen somewhere.  We get to choose whether they have all the fun.

Bio-ERA: Thinking Ahead

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Bio Economic Research Associates has now published its first report examining possible outcomes of a flu pandemic, Thinking Ahead: Anticipating Early Impacts of an Avian Influenza Pandemic.  The report, and the associated research service, are designed to help answer the following questions:

  • What key indicators and signposts should the business community be watching with respect to pandemic influenza?
  • If human transmissible H5N1 broke out in Asia, what specific actions (travel advisories, quarantines, travel restrictions, etc.) should we expect to be implemented by governments and public health authorities?
  • How would these actions impact regional and global economies, and businesses operating within and/or interconnected with, affected regions?
  • How would these developments affect investors and financial markets?

ProMED-mail

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If you want up to the minute information about emerging diseases, ProMED-mail is a service run by the International Society for Infectious Diseases and the Federation of Americal Scientists (FAS).  The FAS also runs ahead/ILIAD, which specifically tracks infectious animal and zoonotic diseases.

There is also link in the "Navigation" bar of the ProMED-mail site to recent medical product and food recalls and medical alerts.

This is good stuff.  But don't read it just before going to bed.

I just stumbled over William Hoffman's World Stem Cell Policy Map, which shows the geographical distribution of policy about stem cells and major genome sequencing centers.  It is part of a larger project to create Global Maps of Human Technological Development, including Global Biotechnology Clusters and Global Biotech Crops.

With the amount of cutting edge research and development taking place in China, India, Taiwan -- the list goes on -- it is interesting to see things laid out this way.  I have concentrated mostly on how technologies are changing in time, and on constructing analogies to help understand what sorts of technologies we need to do better biology.

But the geographical perspective is instructive.  There are obvious clusters of research, some of which lie in countries that are dramatically more permissive about clinical trials than is the US.  It wouldn't take that much in the way of resources to plunk down a cutting edge center in most of the blank areas of the map.  I hope Mr. Hoffman keeps things updated so we can see how the maps develop.

Nanobacteria in the News

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When I showed Sydney Brenner the first paper claiming a physiological role for nanobacteria ("Nanobacteria: an alternative mechanism for pathogenic intra- and extracellular calcification and stone formation", Kajander and Ciftcioglu, PNAS, 95 (8274-8279), 1998), he just chuckled.  And rightly so, given the expansive claims of that and succeeding papers.  Early claims that 30 nanometer particles visible in electron microscopy experiments contained DNA were challenged when the resulting sequences were shown to be identical to those found in common bacterial laboratory contaminants.  That is, while the original work pointed to some interesting evidence, there wasn't enough meat on the bone to convince people who have been watching biology since its modern beginnings.

Work has continued, however, and now careful studies have demonstrated nano sized objects at the core of structures from human bodies, where those nano objects definitely contain DNA.  In "Evidence of nanobacterial-like structures in calcified human arteries and cardiac valves" (Am J Physiol Heart Circ Physiol 287: H1115-H1124, 2004), Miller et al examine a variety of human tissues removed during surgery and conclude that "nanometer-scale particles similar to those described as nanobacteria isolated from geological specimens and human kidney stones can be visualized in and cultured from calcified human cardiovascular tissue."

The paper describes using light and scanning electron microscopy, immunostaining, and DNA staining to characterize objects 30-150 nm in size that appear in physiological samples.  Interestingly, there is already a commercial antibody available, "8D10", that appears to recognize a ~50-kDa protein only found in tissues and cultures that were observed to contain the nanobacteria.  Moreover, simultaneous immunostaining using 8D10 and DNA staining using PicoGreen revealed that structures cultured from filtered homogenates of human aneurysm contained both protein and DNA.  The most compelling evidence from a traditional biology perspective is that the nanobacteria can be propagated in culture media.  That is, the structures are self-replicating.  Decalcified particles contained structures that appear akin to cell membranes.

By way of acknowledging alternative explanations for their data, the authors note that;

Although a unique nucleic acid sequence remains to be identified from the nanosized particles identified within human arterial tissue in the present report, it is possible that these structures may represent either a variant form of microorganisms or an unrecognized bacterial growth stage such as L-forms, cell wall-deficient bacteria, and/or defective bacteria that have been hypothesized to represent either pleuropneumonic-like organisms or Mycoplasma species, which have been detected in serum of patients with long histories of chronic diseases. They may also represent an Archaea symbiont that requires cell contact or lipids from other cells for growth.

They go to observe their data are consistent with nanobacteria as a cause of disease;

Nanobacteria derived from bovine serum are internalized by human cells and appear to be cytotoxic. Similar internalization of nanolike particles in arterial smooth muscle would be consistent with induction of apoptosis, formation of matrix vesicles, and the inflammatory basis of atherogenesis. An infectious etiology of arterial calcification is consistent with increased lesion formation in experimental models of atherosclerosis.

Note that this text implies nanobacteria may be infectious agents.  Miller et al lay out the test of this hypothesis;

...A definitive cause and effect relationship needs to be established between these nanoparticles and [pathogenesis]. For example, it will be necessary to evaluate severity of calcification and disease progression in the absence, presence and titer of nanoparticles in humans. In the experimental setting, it will require infection of a naïve animal with cultured nanoparticles and subsequent identification of the particles within arterial calcification. Definitive characterization of these unique particles will require isolation and sequencing of genetic material (DNA or RNA).

No doubt the debate over nanobacteria will continue until the above criteria are met, but the Miller paper definitely contributes significantly to the discussion.

In the end, this sort of report illustrates how naive we are about what organisms inhabit the human ecosystem.  We haven't even isolated all the viruses and "normal" bacteria that live in and on humans.  And then something strange like nanobacteria come along.  We have lots of work to do.

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