"Playing God in Running Shoes"

Here is Carolyn Abraham's article about Synthetic Biology from the Toronto Globe and Mail, "Playing God in Running Shoes (subscription required to get past the first page)."  Full text here, no subscription required.  Note: I'm not a professor at the UW, as suggested in the article, but rather a senior scientist in the Electrical Engineering Department.  Otherwise, a fine article that goes into not just the technical difficulty inherent in building new organisms but also explores ethical implications of the whole endeavor.  I'm not so sure, though, how Drew Endy is going to feel about being described in the story title that way...

The Costs of Complying with Open Source

The International Herald Tribune has a story by Kevin O'Brien on the costs associated with open source software, "In open source, an unexpected trap".  The future of Open Source Biology will include similar costs.

The article relates several episodes in which companies have included open source code in products without then publishing the resulting code appropriately as dictated by the relevant license.  These infractions have resulted in efforts by coders to push for compliance, and also spawned a new market segment for services that screen for open source code in commercial products.  Palamida, for example, provides code due diligence for a fee.

This is another example of the interesting legal and practical landscapes created by open innovation.  The main message of the O'Brien article for me is that open source continues to be a way for companies to reduce development costs.  And this requires figuring out ways to use open source code effectively, intelligently, and legally.  If code created by the masses is close enough to a solution required by Cisco, Intel, or IBM, it seems the Fortune 500 has no difficulty justifying the use of technology that results from open innovation.  Open source doesn't seem to be killing off traditional companies, as claimed by some large organizations; instead, it's helping the companies that adapt to thrive.  The use of the open source code to reduce costs, and the existence of Palamida, suggest the market is providing the solutions to make open source work.

And if the strategy works for electrons, why not for molecules?  If it works for hardware, why not wetware?  Most relevant to the IHT article, I wonder about verifying compliance with biological versions of open source licenses.  There will obviously be companies spun up to analyze the contents of molecular systems -- genomes, proteomes, in vitro enzymatic cocktails -- just as compliance has become an issue for software companies.

This gets one thinking a bit deeper about the challenges of ensuring compliance.  I suspect open source wetware is like open source hardware, in that compliance probably requires a suite of physical tools that enable one to pick apart the molecular contents of a system unambiguously.  I wrote a few days ago about Intel's Sun's release of the Verilog code for the UltraSPARC T1 chip under and open source license; how are they going to police all the chips out there to make sure some of their code isn't used by a competitor?  Or even in a chip that is used for something else entirely?  If the code for the offending chip isn't published, you would have to subject the chip to all sorts of tests, from running test vectors on the chip to sticking the thing under an electron microscope to directly examine the architecture.

Similarly, looking under the hood of a synthetic biological system to check for open source license compliance will require identifying physical objects and proving their use either is consistent or conflicts with the terms of the license.  Another motivation for better biological test and measurement gear.

If Palamida exists primarily because big corporations don't want to get sued, then I wonder if a biological version -- a service company, say -- can assemble the appropriate tools based on funding from big corporations that want to ensure they are complying with Open Source Biology licenses.  Plus user fees from inventors and developers trying to ensure they get paid?  Interesting.

Sun Tries Open Hardware Development, and India Pushes Open Biology

India is compiling an open, on-line encyclopedia of traditional medical knowledge.  In "India hits back in 'bio-piracy' battle", Soutik Biswas reports for the BBC that, in the last decade, India has found itself working to overturn Western patents on uses of compounds that have been known for centuries by domestic healers.  This prior art is the accumulation of generations of effort, and it is understandable that a population that makes use of traditional medicines might be a tad peeved that their work is being stolen. 

Biswas describes an effort to make the knowledge easily accessible:

The ambitious $2m project, christened Traditional Knowledge Digital Library, will roll out an encyclopaedia of the country's traditional medicine in five languages - English, French, German, Japanese and Spanish - in an effort to stop people from claiming them as their own and patenting them.

A major motivation for putting all this information in writing is that the oral component of traditional Indian teaching and knowledge is not acknowledged withing Western Intellectual Property law:

Under normal circumstances, a patent application should always be rejected if there is prior existing knowledge about the product. ...But in most of the developed nations like United States, "prior existing knowledge" is only recognised if it is published in a journal or is available on a database - not if it has been passed down through generations of oral and folk traditions.

There is obviously a great deal of value in this accumulated wisdom:

Dr Vinod Kumar Gupta, who is leading the traditional wealth encyclopaedia project and heads India's National Institute of Science Communication and Information Resources (Niscair), reckons that of the nearly 5,000 patents given out by the US Patent Office on various medical plants by the year 2000, some 80% were plants of Indian origin.

By one estimate, a quarter of the new drugs produced in the US are plant-based, giving the sometimes much-criticised practitioners of alternative traditional medicine something to cheer about.

Which suggests an additional effect of the library: those inclined to self-medicate will have a tremendous resource for treating what ails them.  We are likely to see an increasing number of people showing up at western clinics and hospitals with a history that includes treatments and compounds not amongst the recognized armamentarium.  Another complication of Open Biology, or Open Source Biology, or whatever we are going to call it.  People are going to use information however they see fit, trying things out, producing improvements occasionally.  It's another matter, of course, as to whether those improvements will be shared.  One can only hope that the tradition of open innovation extends to such novel medical treatments.

Sun Microsystems appears to be explicitly counting on this behavior to provide improvements in their UltraSPARC T1 processor.  By open-sourcing the VERILOG design code (eWeek news story) for the chip (OpenSPARC), Sun is hoping the masses can produce more innovation than Sun itself.  The press release makes interesting, if flowery, reading.  "If it works in software, why wouldn't it work for processors?" asks Chairman Scott McNealy, as quoted in the eWeek article.

The most interesting part of the whole story is the strategy to promote innovation around the chip, and then potentially bring those innovations in house.  Jeffrey Burt, in the eWeek article writes:

Sun already has shown the ability to bring in key technologies through acquisitions—indeed, the groundwork for the T1 chip was developed by another company, Afara Websystems Inc., which Sun bought in 2002. McNealy said he envisioned a future where companies will be created to develop technologies around UltraSPARC T1, and then be acquired by Sun. (emphasis added)

If this strategy works for hardware, why not wetware?  If it works for electrons, why not molecules?  I speculated about this in an earlier post, Acquiring Open-Source Projects.  It appears that with the OpenSPARC project we will have another example of how to encourage innovation, and we will find out whether a commercial entity can profit from so explicitly sharing the fruits of its labor.

"There is no scientifict basis to predict [the course of the avian flu]".

There is an excellent news story by Dennis Normile in the 18 November 05 issue of Science about  present uncertainty over the course of the avian flu, "Pandemic Skeptics Warn Against Crying Wolf".

As I have written here previously (for example, "How long does it take the flu to evade a vaccine?"), we have very little data on the evolution of pandemic flu viruses.  For instance, we can't make general conclusions about the intervals between pandemics because there just aren't many data points.  Moreover, historical pandemic strains are quite different from each other, with some being obviously of avian origin while others arose through recombination or reassortment of avian and mammalian strains.  Differences amongst the viruses also obscure the mechanism(s) by which pandemic strains arise.

In the lead for his article, Normile asks, "Is the H5N1 virus now circulating in Asia really the one to watch? How soon will the next pandemic occur? And will it trigger a wave of mortality, as did the 1918 flu, or a just small ripple in the annual influenza death toll?"  He quotes well known virologists and evolutionary biologists as doubting whether the presently circulating H5N1 flu bug has the capacity to become a pandemic strain.  The article then delves into the role of World War I in generating and spreading the 1918 virus.

Most interesting for me, however, are the straightforward comments concerning how little we know about what is going on:

Although the historical data are interesting, [Mary Lipsitch of Harvard] and others add, they simply aren't conclusive enough to rule an H5N1 pandemic in or out. "We don't know what viruses circulated in the past [among humans], except for the most recent 150 years," says Yoshihiro Kawaoka, a virologist at the University of Tokyo and the University of Wisconsin, Madison. What's more, he says, H5N1 is shattering historical precedents. Never before has a virus so highly lethal for poultry become so widespread and continued in circulation for such a long time. And with the virus continuing to spread, "the risk of mutation is increasing accordingly," says Masato Tashiro, director of WHO's Collaborative Center for Influenza Surveillance and Research at Japan's National Institute of Infectious Diseases in Tokyo. There are so many gaps in what is known about how virulence and pathogenicity evolve, Kawaoka says, that "there is no scientific basis to predict anything." (emphasis added)  [The University of Washington's Carl Bergstrom] agrees: "We, as scientists, need to do a good job of something slightly tricky here, which is to convey that our predictions are probabilistic."

Not an easy job, particularly when politicians demand (and promise) unrealistic certainty and the public has an ever poorer understanding of the very nature of science.  But because pandemics do historically occur, everyone who knows anything about the flu agrees we need to prepare for the future.  The article concludes:

[Paul Offit, of the University of Pennsylvania School of Medicine] hopes the concerns about H5N1 will lead to efforts to strengthen the U.S. infrastructure for vaccine development and production, which he says has deteriorated over the last 50 years. He thinks the message scientists should be sending "is not that we're going to protect you from the bird flu pandemic, but that we're going to be protecting you from a pandemic which may be 20 years from now."

As if that weren't enough to worry about, Oliver Sacks reminds us that the 1918 flu was accompanied by at least one other disease that under other circumstances would have itself been seen as a tragic pandemic.  In "Waking to a New Flu Threat" (NY Times, 16 November 05), Sacks and Joel Vilensky note:

The influenza pandemic of 1918 was followed by another epidemic. The disease was encephalitis lethargica, or the "sleepy sickness," and like influenza it spread through most of the world. Its symptoms were extraordinarily varied - most commonly there was lethargy, but sometimes there was insomnia, and even frenzy; sometimes there were paralyses, sometimes mental disorders...  In 1982 it was shown that irregularly spaced waves of influenza-pneumonia deaths in Seattle during the early 20th century epidemic were followed approximately one year later by corresponding waves of encephalitis fatalities.

...No cure or causative agent had ever been found and most of the remaining survivors were housed in chronic-care hospitals and forgotten.

...No funds have been allocated to try to better understand this mysterious disease and its relationship to epidemic influenza. Encephalitis lethargica is a particularly insidious disease because it is so variable; any early cases in a new outbreak would almost certainly be misdiagnosed as they were 100 years ago.

It is not unlikely that this disease will return. Perhaps with the imminent influenza epidemic, perhaps not. Regardless, we would do well to re-awaken ourselves to what may be a formidable gathering threat.

Which, as I watch the sun set over Mt. Rainier, Lake Union, and downtown Seattle, will not help me sleep any better tonight.

Direct Biological Production of Diesel

Based on the number of Google searches that lead to my post Algae into Biodiesel, there seems to be significant interest in direct biological production of diesel.  National Geographic, c|net, and Technology Review all have carried stories recently about new approaches for generating biofuels and new catalysts for reducing costs and improving yield.

Perhaps this research will finally help land a turbo diesel roadster on my doorstep.

Avian Flu, and vaccination, in China

Everyone has probably  heard that China has confirmed human cases of the H5N1 flu ("China Reports Second Bird Flu Death", Reuters via NY Times).  The Chinese government now acknowledges that they have a "serious epidemic" (CNN), and has culled more than twenty million birds in response to localized outbreaks.

In an attempt to keep control of the situation, "China Threatens Police Action in Fight on Bird Flu" (Reuters via NY Times).  I find particularly interesting the new regulations forbidding actions that restrict accurate reporting of the progress of the virus; "Any practices which affect the reporting of epidemic diseases, including deception, false or late reporting, are forbidden," according to Vice Agriculture Minister Yin Chengjie.  As I wrote last spring (The Economic Consequences of Chinese Pandemic Un-Preparedness), the structure of governmental power in China appears to have changed significantly over the last few years.  According to people who spend significant amounts of time in country, the central government is no longer able to exert much authority over local governments, nor can it count on accurate information coming in from the provinces.  It will be interesting to see if the new regulations have an impact on disease reporting.  With less than clear initial explanations of the enormous benzene spill near Harbin (NY Times), it may be awhile before up front communication is the norm.

The government has also announced plans to vaccinate 14 billion birds to combat further spread.  Of course, the first question everyone is asking is where they are going to come up with that much vaccine.  Everyone in the west seems to agree that the domestic Chinese poultry vaccine production capacity is only in the neighborhood of several hundred million doses annually, which suggests they face significant challenges in vaccinating more than 10 billion birds anytime soon.  An article in the International Herald Tribune casts doubt on the feasibility of this strategy, with veterinary experts expressing blunt skepticism; "Dr. Leon Russell, president of the World Veterinary Association, said '..For the life of me, I can't figure out how China will vaccinate billions of chickens'."

(UPDATE 28 November 05):  Last Thursday's Nature has a short news piece claiming that China has already vaccinated 8 billion birds and that "the country's ten vaccine producers can make 16 billion doses of vaccine per year".  That is quite a contrast to other numbers I've read, and definitely disagrees with the rest of this post.

Wired Magazine's version of the Global DNA Foundry Map

Wired 13.12 (December 2005) contains the magazine's version ("A Genome Shop Near You") of the Global Distribution of Commercial DNA Foundries map I helped make this past summer.  Not all of the foundries on my map are on Wired's version, and they found a few more, but the gist is the same.  Jerry Epstein and Anne Yu at the Center for Stratetic and International Studies contributed to making the original map.

Phase I Results of PowderMed's H3 DNA Vaccine

I'm still stuck waiting for publication of the relevant journal paper, but I now have a copy of poster presented by PowderMed earlier this year.

The summary: with 1, 2, and 4 microgram injections of an H3 gene vaccine via gene gun, PowderMed has shown that even the single microgram dose was safe and generated an anti-influenza antibody response.  Each dose was trialed on a group of 12 volunteers.  "The titres achieved at day 21 of the 4 microgram dose group were sufficient to meet the requirements of the CHMP [Committee for Medical Products for Human Use of Europe] for licensing of annual influenza vaccines."  Thus falls the "primate barrier" to DNA/gene vaccines.

As I understand it, human challenge trials for H3 Panama influenza will begin early next year.  So the pieces are falling into place, but there seems to be so much unfounded resistance against DNA/gene vaccines that it may take a painfully long time just to get funders and regulators tuned in to the possibilities.

I'll post more here when additional trial data is no longer embargoed.

Bio-ERA's US Senate Testimony on Pandemic Flu

Last week Jim Newcomb, my colleague from Bio Economic Research Associates (www.bio-era.net), testified before the Senate Foreign Relations Committee on potential economic damage from a flu pandemic.  Here is the PDF (bio-era, US Senate), replete with excellent figures.  Much of the testimony is based on extensive analysis by bio-era of the SARS episode.  The upshot for the flu is that fear induced by infectious disease can cause significant damage by itself.  The SARS virus killed just short of 800 people and cost as much as $50 billion.  The H5N1 avian flu had by March 2005 already caused an estimated $10 billion in damage, with those costs now much higher and sure to rise even if the bug doesn't evolve to become more infectious in humans.