Heading to MIT and iGEM

I'm off to give a talk at MIT on Friday and be a judge for iGEM again this weekend.

Here are talk coordinates (I've no idea how big the room is):

"Engineering (and) the Bio-economy"
Rob Carlson

7 November, 2008
12 to 2 PM
MIT
E38, 6th floor conference room.
292 main street, directly above the MIT press book store.

Can't wait to see what the students have come up with this year.

Update on Influenza Subtype Activity in 2007-2008

While addressing some comments from Ralph Baric on one chapter my book, I had reason to go find statistics on influenza subtype activity last year.  Those interested in keeping up on recent flu activity should peruse this July, 2008, report from the CDC: Influenza Activity --- United States and Worldwide, 2007--08 Season.

Here is the breakdown on subtype activity:

During September 30, 2007--May 17, 2008, World Health Organization and National Respiratory and Enteric Virus Surveillance System collaborating laboratories in the United States tested 225,329 specimens for influenza viruses; 39,827 (18%) were positive. Of the positive specimens, 28,263 (71%) were influenza A viruses, and 11,564 (29%) were influenza B viruses. Among the influenza A viruses, 8,290 (29%) were subtyped; 2,175 (26%) were influenza A (H1N1), and 6,115 (74%) were influenza A (H3N2) viruses. The proportion of specimens testing positive for influenza first exceeded 10% during the week ending January 12, 2008 (week 2), peaked at 32% during the week ending February 9, 2008 (week 6), and declined to <10% during the week ending April 19, 2008 (week 16). The proportion positive was above 10% for 14 consecutive weeks. The peak percentage of specimens testing positive for influenza during the previous three seasons ranged from 22% to 34% and the peak occurred during mid-February to early March. During the previous three influenza seasons, the number of consecutive weeks during which more than 10% of specimens tested positive for influenza ranged from 13 to 17 weeks.

Of note, 26% of samples positive for influenza were the H1N1 subtype -- the same as the 1918 flu -- which means we all have probably been exposed to it and have some immunity.  That does not mean the particular combination of genes in the 1918 flu would be harmless if it showed up again, but rather than our immune systems should be able to better recognize that bug and thus might defend against it better than the first time around.

Land Reform in China

The IHT is carrying news of a new land policy in China.  Here is the lead:

Chinese leaders approved on Sunday a policy that will in theory allow peasants to buy and sell their land rights, a move that sets in motion the nation's biggest economic reform in many years, according to a report by Xinhua, the state news agency.

The print version I picked up in Hong Kong today is a bit different.  It carries this crucial bit of information:

The government's goal is to double the per-capita disposable income of rural residents by 2020 from the 2008 level, according to Xinhua.

It is unclear how much the plan is intended to increase total per capita income in rural areas.  I think this is particularly important because it will strongly influence how much almost 800 milllion people (according to the article) have to spend on food.  Implementing the land reform plan may put a time scale on the increase in food demand that I speculated about recently in "More on China's Economy, Food Production, and Food Demand".

If the numbers in that post are mostly correct, this would mean that if China is going to stay self-sufficient with respect to food supply needs to increase its domestic production by something like 20% in the next 11 years.  They have their work cut out.

Synthetic Biology 4.0 – Not so live blog, part 1

What a difference a few years makes.  SB 1.0 was mostly a bunch of professors and grad students in a relatively small, stuffy lecture hall at MIT.  SB 2.0 in Berkeley expanded a bit to include a few lawyers, sociologists, and venture capitalists.  (I skipped 3.0 in Zurich.)

At just over 600 attendees, SB 4.0 is more than twice as big as even 3.0, with just under half the roster from Asia.  The venue, at the Hong Kong University of Science and Technology, is absurdly nice, with a view over the ocean that beats even UCSB and UCSD.  Kudos also to the organizers here.  They worked very hard to make sure the meeting came off well, and it is clear they are interested in synthetic biology, and biotech in general, as a long term proposition.  The Finance Minister of Hong Kong, John Tsang, spoke one evening, and he was very clear that HK is planning to put quite a lot of money and effort into biology.

Which brings me to a general observation that Hong Kong really cares about the future, and is investing to bring it along that much sooner.  I arrived a day early in order to acclimate a bit and wander around the city, as my previous visit was somewhat hectic.  Even amid the financial crisis, the city feels more optimistic and energetic than most American cities I visit.

I will have to write up the rest of the meeting when I get back to the States later this week.  But here are a few thoughts:

As of the last few days, I have now seen all the pieces necessary to build a desktop gene printer.  I don’t have prediction when such a thing will arrive on the market, but there is no doubt in my mind that it is technically feasible.  With appropriate resources, I think it would take about 8 weeks to build a prototype.  It is that close.

Ralph Baric continues to do work on SARS that completely scares the shit out of me.  And I am really glad it is getting done, and also that he is the one doing it.  His work clearly demonstrates how real the threat from natural pathogens is, and how poorly prepared we are to deal with it.

Jian Xu, who is better known for his efforts to understand the human gut microbiome, spoke on the soup-to-nuts plant engineering and biofuels effort at the Qingdao Institute of Bioenergy and Bioprocess Technology, run by the Chinese Academy of Sciences (QIBEBT).   The Chinese are serious about putting GM plants into the field and deriving massive amounts of energy from biomass.

Daphne Prauss from Chromatin gave a great talk about artificial chromosomes in plants and how they speed up genetic modification.  I’ll have to understand this a bit better before I write about it.

Zach Serber from Amyris spoke about on their biofuels efforts, and Amyris is on schedule to get aviation fuel, diesel, and biogasoline into the market within the next couple of years.  All three fuels have equivalent or better characteristic as petro-fuels when it comes to vapor pressure, cloud point, cetane number, octane, energy density, etc.

More soon.

Off to Synthetic Biology 4.0 in Hong Kong

Tomorrow I am off to SB 4.0 in Hong Kong.  I will be leading a lunchtime workshop on "Commercialization of Genetic Parts".

Here is the abstract:

Synthetic Biology presently finds most of its participants in academia. Yet many applications, for example fuels, drugs, and materials, will be developed and used within a very different context than universities and other non-profit organizations. How can we spin up an economy based on composable parts that people can actually use to pay the rent in one way or another?

I expect the direction of the discussion will be guided mostly by who actually shows up.  If we wind up talking about Biobrick Parts (TM), then we will need to hear more about whatever license the Foundation is trying to put together.  My understanding is that the details of this license are still under wraps, so the discussion could well focus instead on how one can commercialize any widget these days.  If that is the way it goes, I'll be happy to share my experiences in exploring the possibilities of garage biology.  Here is the short version: Building a prototype is not so bad, and contract manufacturing is a royal pain in the ass to get going.  So it's just like the rest of the economy...

Assuming we have decent web access, I will be blogging during the meeting.  Stay tuned.

Company Profile: Blue Marble Energy

A couple of months ago I met the founders of Blue Marble Energy at a party for the Apollo Alliance.  Following up, I sat down with the CEO, Kelly Ogilvie, to learn about Blue Marble, which is the only "algal biofuel" company I have come across that really makes sense to me.  (While at the party, I also chatted with Congressman Jay Inslee for quite a while.  Smart fellow.  Anyone interested in energy policy should have a look at his book, Apollo's Fire: Igniting America's Clean Energy Economy.)

Full disclosure: Blue Marble and Biodesic may begin collaborating soon, so I am not an entirely disinterested observer.

Blue Marble Energy is built around the idea of "recombining" existing biological processes to turn biomass into valuable products.  From the website: "[Blue Marble Energy] uses anaerobic digestion to generate natural gas and other valuable bio-chemical streams."  The company is distinguished from its competitors by its focus on using micro- and macro-algae harvested from natural blooms, including those caused or enhanced by human activity, as feedstock for artificial digestion systems modeled on those of ruminants.  Blue Marble combines different sets of microbes in a series of bioreactors to produce particular products. 

In other words, Blue Marble is using industrialized, artificial cow stomachs to produce fuel and industrial products.

The company's general strategy is to first digest cellulose into synthesis gas (carbon dioxide and hydrogen) using one set of organisms, and then feed the synthesis gas to organisms that generate methane or higher margin chemicals and solvents.  The company expects to produce 200-300 cubic meters of methane per wet ton of algal feedstock.  While biofuels are an obvious target for technology like this, the company also recognizes that fuels are a low margin commodity business.  Thus Blue Marble also plans to produce higher margin industrial products, including solvents such as various esters that sell for $400-800 per gallon.

While other companies are attempting to directly produce fuels from cultured algae, Blue Marble believes these efforts will be hampered by growth limitations in most circumstances.  Biofuel production from algal lipids synthesized during photosynthetic growth requires conditions that cause metabolic stress, resulting in lipid production, but that also limit total biomass yield to ~2-5 grams per liter.  In contrast, Blue Marble "respects the complex ecology", in the words of Mr. Ogilvie, and relies on photoheterotrophic growth of whatever happens to grow in open water.

Blue Marble has already obtained contracts to clean up algal growth caused by human activity around Puget Sound.  The company typically harvests ~100 grams per liter from these "natural" algal blooms.  Future plans include expanding these clean up operations around the U.S. and overseas, and growing algae in wastewater, which would provide a high-energy resource base for both closed and open system growth.  In principle, because the technology is modeled on ruminant digestion, many different sources of biomass should be usable as feedstock.  Experience thus far indicates that feedstocks with higher cellulose content result in higher yield production of fuels and solvents.

Compared with other algal biofuel companies, Blue Marble does not presently require high capital physical infrastructure for growing algae.  However, the company will rely on marine harvesting operations, which bring along a different set of complexities and costs.  I wonder if the company might be best served if it outsourced harvesting activities and focused on the core technology of turning biomass into higher value products.

While the Blue Marble is not now genetically modifying their production organisms, this will likely prove a beneficial move in the long term.  Tailoring both the production ecosystem and the metabolisms of component organisms will certainly be a goal of competitors, as is already the case with companies spanning a wide range of developmental stages, including DuPont, Amyris, and Synthetic Genomics.  Yet whereas modified production organisms grown in closed vats are likely to face little opposition on any front, genetically modified feedstocks grown in open waters are another matter.  For the time being, Blue Marble has an advantage over plant genomics companies because in the company's plans to use unmodified biomass as feedstock, whether algae or grasses, it will avoid many regulatory and market risks facing companies that hope to grow genetically modified feedstocks in large volumes. 

They have a long way to go, but in my judgement Blue Marble appears to have a better grasp than most on the economic and technical challenges of using algae as feedstock for fuels and materials.

Further reading:

"It came from the West Seattle swamp - to fill your tank", Eric Engleman, Puget Sound Business Journal, August 8, 2008

"Swamp fever", Peter Huck, The Guardian, January 9 2008
http://www.guardian.co.uk/environment/2008/jan/09/biofuels.alternativeenergy

"New wave in energy: Turning algae into oil", Erica Gies, International Herald Tribune, June 29, 2008

Methane Time Bomb Update

Following on its coverage of an expedition to Russia's northern coast that found methane deposits leaking through melting permafrost into the water and atmosphere, The Independent has news that a British expedition to the seas off the coast of Norway has discovered "hundreds of methane plumes".  From the article:

Yesterday, researchers on board the British research ship the James Clark Rosssaid they had counted about 250 methane plumes bubbling from the seabed in an area of about 30 square miles in water less than 400 metres (1,300 feet) deep off the west coast of Svalbard. They have also discovered a set of deeper plumes at depths of about 1,200 metres at a second site near by.

The story notes that "It is likely that methane emissions off Svalbard have been continuous for about 15,000 years – since the last ice age."  I think it is fascinating that these plumes have only just been discovered.  This means the methane budget of the atmosphere is probably still quite poorly understood, even as it is clear new sources of methane are opening due to climate change.

Cleaning out some bookmarks

In no particular order of importance:

  • Metbolix has announced it has modified switchgrass to produce PHA.  The "Mirel history" page on the website suggests there are 7 enzymes in the pathway.  An independent Life Cycle Analysis of Mirel, "Conducted by Dr. Bruce Dale, professor of Chemical Engineering at Michigan State University, determined that production of Mirel reduces the use of nonrenewable energy by more than 95% and provides a 200% reduction in greenhouse gases (GHG) compared to production of conventional petroleum-based plastics. concluded."  (PDF Press release)
  • Here is an essay from Jeremy Haft (WSJ via Huffington Post) that opines the US has a permanent competitive edge over China.  Really?
  • A couple of posts from Wired on saving our economy with a cleantech/greentech bubble.  'Cuz bubbles really keep us afloat.  Until they pop.  And we write $700 billion dollar checks.  Right... 

"Methane time bomb"

The Independent carried a story on Tuesday that should alarm anyone interested in climate change (anthropogenic or otherwise).

"Exclusive: The methane time bomb", by Steve Connor, describes a just concluded methane sampling expedition along "the entire length of Russia's northern coast".  Interested readers should just follow the link to get the whole story.  To summarize: warming waters are releasing so much methane from previously trapped deposits that in some areas the seas are literally foaming as gas bubbles up from below.  Previous sampling cruises in the area have detected increasing concentrations of dissolved methane in water, but apparently methane deposits are escaping at an increasing rate.  Here is a good number from the article to keep in mind: the arctic region as a whole has warmed 4 degrees C in the last decade.

Since the release is caused by melting permafrost, there isn't much we can do to stop it.  So, given that methane is a much more powerful greenhouse gas than carbon dioxide, we might want to give some thought to attempting a fix.

Jamais Cascio has been following this threat for quite a while, and extends here his thoughts on dealing with atmospheric methane using geo-engineering using bio-engineered microbes.

Jamais writes:

The most conservative estimates I've seen start at around 70 billion metric tons of methane -- the equivalent in greenhouse terms to 1.6 trillion metric tons of CO2. As a point of comparison, the total annual greenhouse footprint in the US is about 7 billion tons; globally, the annual footprint is about 30 billion tons.

If this methane leak continues to increase, we may be facing a disastrous result that no amount of renewable energy, vegetarianism, and bicycling will help. This is one scenario in which the deployment of geoengineering is over-determined, probably needing to remain in place for quite a while as we try to remove the methane (or, at worst, wait for it to cycle out naturally over the course of a decade or so). It's also a scenario that might require large-scale use of bioengineering.

That would be, to put it lightly, an extremely hard project.  And we are nowhere near ready to start.  Happy Thursday.

"Coskata Due Diligence"

Oliver Morton at Nature pointed me to a bunch of excellent posts on Coskata by Robert Rapier at R-Squared.  Recall that Coskata wants to gasify cellulose and feed the resulting synthesis gas to bugs that make ethanol.  Here are Rapier's "Coskata"-tagged posts.

Among other points, Rapier makes some nice back of the envelope estimates of the technical and economic feasibility of Coskata's process.  In short, Coskata's claims appear to be consistent with the laws of thermodynamics, but perhaps not so much with the law of supply and demand, and their logistics challenges might border on being inconsistent with the consevation of matter.

Basically, it all, err, "boils down" to the fact that Coskata is probably going to get tripped up by their focus on ethanol and the consequent energy cost of separating ethanol from water.  Even if you have a nifty process for turning cellulose into ethanol, it takes a large fraction of the energy in the cellulose to purify the ethanol.  And it really doesn't matter whether you distill or use a membrane -- the entropy of mixing still hoses you even if you somehow escape the specific heat of water and its enthalpy of vaporization.

Now if you hacked the metabolic pathway that consumes synthesis gas so that the bug made something more interesting like butanol, or a gasoline analog, that either had lower miscibility or even phase separated, that would really be something because it would minimize the energy cost of purification.

Great work, Mr. Rapier.  And many thanks, Oliver.