And the Innovation Continues...Starting with Shake and Bake Meth!

My first published effort at tracking the pace and proliferation of biological technologies (PDF) was published in 2003.  In that paper, I started following the efforts of the DEA and the DOJ to restrict production and use of methamphetamine, and also started following the response to those efforts as an example of proliferation and innovation driven by proscription.

The story started circa 2002 with 95% of meth production in Mom and Pop operations that made less than 5 kg per year.  Then the US Government decided to restrict access to the precursor chemicals and also to crack down on domestic production.  As I described in 2008, these enforcement actions did sharply reduce the number of "clandestine laboratory incidents" in the US, but those actions also resulted in a proliferation of production across the US border, and a consequently greater flow of drugs across the border.  Domestic consumption continued to increase.  The DEA acknowledged that its efforts contributed to the development of a drug production and distribution infrastructure that is, "[M]ore difficult for local law enforcement agencies to identify, investigate, and dismantle because[it is] typically much more organized and experienced than local independent producers and distributors."  The meth market thus became both bigger and blacker.

Now it turns out that the production infrastructure for meth has been reduced to a 2-liter soda bottle.  As reported by the AP in the last few days, "The do-it-yourself method creates just enough meth for a few hits, allowing users to make their own doses instead of buying mass-produced drugs from a dealer."  The AP reporters found that meth-related busts are on the increase in 2/3 of the states examined.  So we are back to distributed meth production -- using methods that are even harder to track and crack than bathtub labs -- thanks to innovation driven by attempts to restrict/regulate/proscribe access to a technology.

And in Other News...3D Printers for All

Priya Ganapati recently covered the latest in 3D printing for Wired.  The Makerbot looks to cost about a grand, depending on what you order, and how much of it you build yourself.  It prints all sorts of interesting plastics.  According to the wiki, the "plastruder" print head accepts 3mm plastic filament, so presumably the smallest voxel is 3mm on a side.  Alas this is quite macroscopic, but even if I can't yet print microfluidic components I can imagine all sorts of other interesting applications.  The Makerbot is related to the Reprap, which can now (mostly) print itself.  Combine the two, and you can print a pretty impressive -- and always growing -- list of plastic and metal objects (see the Thingiverse and the Reprap Object Library).

How does 3D printing tie into drug proscription?  Oh, just tangentially, I suppose.  I make more of this in the book.  More power to create in more creative people's hands.  Good luck trying to ban anything in the future.

Data and References for Longest Published sDNA

Various hard drive crashes have several times wiped out my records for the longest published synthetic DNA (sDNA).  I find that I once again need the list of references to finish off the edits for the book.  I will post them in the open here so that I, and everyone else, will always have access to them.

longest sDNA 2008.png

Year Length Refs
1979 207 Khorana (1979)
1990 2100 Mandecki (1990)
1995 2700 Stemmer (1995)
2002 7500 Cello (2002)
2004.4 14600 Tian (2004)
2004.7 32000 Kodumal (2004)
2008 583000 Gibson (2008)

1979
Total synthesis of a gene
HG Khorana
Science 16 February 1979:
Vol. 203. no. 4381, pp. 614 - 625
http://www.sciencemag.org/cgi/content/abstract/203/4381/614

1990
A totally synthetic plasmid for general cloning, gene expression and mutagenesis in Escherichia coli
Wlodek Mandecki, Mark A. Hayden, Mary Ann Shallcross and Elizabeth Stotland
Gene Volume 94, Issue 1, 28 September 1990, Pages 103-107
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T39-47GH99S-1J&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=84ca7779ff1489d5e18082b9ecb80683

1995
Single-step assembly of a gene and entire plasmid from large numbers of oligodeoxyribonucleotides
Willem P. C. Stemmer, Andreas Crameria, Kim D. Hab, Thomas M. Brennanb and Herbert L. Heynekerb
Gene Volume 164, Issue 1, 16 October 1995, Pages 49-53
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T39-3Y6HK7G-66&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=83620e335899881aac712a720396b8f2

2002
Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template
Jeronimo Cello, Aniko V. Paul, Eckard Wimmer
Science 9 August 2002: Vol. 297. no. 5583, pp. 1016 - 1018
http://www.sciencemag.org/cgi/content/abstract/1072266

2004
Accurate multiplex gene synthesis from programmable DNA microchips
Jingdong Tian, Hui Gong, Nijing Sheng, Xiaochuan Zhou, Erdogan Gulari, Xiaolian Gao & George Church
Nature 432, 1050-1054 (23 December 2004)
http://www.nature.com/nature/journal/v432/n7020/full/nature03151.html

Total synthesis of long DNA sequences: Synthesis of a contiguous 32-kb polyketide synthase gene cluster
Sarah J. Kodumal, Kedar G. Patel, Ralph Reid, Hugo G. Menzella, Mark Welch, and Daniel V. Santi
PNAS November 2, 2004 vol. 101 no. 44 15573-15578
http://www.pnas.org/content/101/44/15573.abstract

2008
Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome
Daniel G. Gibson, Gwynedd A. Benders, Cynthia Andrews-Pfannkoch, Evgeniya A. Denisova, Holly Baden-Tillson, Jayshree Zaveri, Timothy B. Stockwell, Anushka Brownley, David W. Thomas, Mikkel A. Algire, Chuck Merryman, Lei Young, Vladimir N. Noskov, John I. Glass, J. Craig Venter, Clyde A. Hutchison, III, Hamilton O. Smith
Science 29 February 2008: Vol. 319. no. 5867, pp. 1215 - 1220
http://www.sciencemag.org/cgi/content/abstract/1151721

Another Step Toward DIYStemCells

(18 June 2009: Lightly edited for clarity.)

The June 5 issue of Cell Stem Cells has a brief report describing the use of four proteins to reprogram human fibroblasts into induced pluripotent stem cells (iPSCs).  I think this is a pretty important paper, as it dispenses with any sort of genetic manipulation of the target cells or any use of plasmids to insert new "control circuitry", or any chemical manipulation whatsoever.

As expected, it is getting easier to produce iPSCs, and the authors of the paper ("Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins") note that their work demonstrates the elimination of "the potential risks associated with the use of viruses, DNA transfection, and potentially harmful chemicals and in the future could potentially provide a safe source of patient-specific cells for regenerative medicine".

Kim et al used four recombinant human proteins to turn human newborn fibroblast cells (purchased from ATCC -- see the Supplemental Data) into iPSCs, where each of the proteins was fused to a nine amino acid long "cell-penetrating peptide" (CPP) that facilitated the importation of the proteins across the cell membrane.  The procedure was not particularly efficient, but after multiple treatments the authors produced cells that could differentiate into many different kinds of human tissues.

Here are a couple of thoughts about the paper.  Note that in what follows I have only had a few sips of my first cup of coffee today, and my brain is still quite fuzzy, but I think I am mostly coherent.  You can be the judge.

First, the authors did not use mature cells from adults, so don't expect this paper to lead to replacement organs and tissues tomorrow.  The use of cells from newborns makes a great deal of sense for a first go at getting protein-based reprogramming to work, as those cells have already been demonstrated to be relatively easy to reprogram.  The published procedure required many weeks of effort to produce iPSCs, and authors note that they have quite a ways to go before they can produce stem cells at the same efficiency as other techniques.

Nonetheless, it works.

Second, the paper describes PCR-based cloning of human genes to add the CPP sequences, along with a fair amount of bench manipulation to generate cells that made each of the four reprogramming proteins.  All the sequences for those proteins are online, as are the sequences for the CPPs, so generating the corresponding genes by synthesis rather than cloning would now cost less than $10K, with delivery in 2-4 weeks.  In another year, it will probably cost no more than $5K.  (How long will it be before these proteins show up in the Registry of Standard Biology Parts?)

Third, the authors did not use purified reprogramming proteins to generate iPSCs, but rather used whole cell extracts from cells that produced those proteins.  Thus the concentrations of the reprogramming proteins were limited to whatever was in the cell extract.  This might critically affect the efficiency of the reprogramming.  Presumably, the authors are already working on generating cultured cell lines to produced the reprogramming proteins in larger quantities.  But if you wanted to do it yourself, it looks like you might "simply" have to order the appropriate sequences from Blue Heron already cloned into the human expression plasmid pCDNA3.1/myc-His A, which is available from Invitrogen.  This would add a couple of hundred dollars to the cost because Blue Heron would have to play around with a proprietary plasmid instead of the public domain plasmids they usually use to ship genes.  You would then follow the recipe from the Supplementary Data to transform a protein production cell line to make those proteins.  Or perhaps you have a favorite recipe of your own.  Here is something I don't get -- it looks like that particular expression plasmid adds a His tag to the end of the gene, so I don't understand why Kim et al didn't try a purification step, but maybe that is underway.

Fourth, if you wanted to do this at home, you could.  You should expect to fail many times.  And then you should expect to fail some more.  And then, assuming your human cell culture technique is up to snuff, you should expect to eventually succeed.  You might want to wait until the inevitable paper showing how to do this with adult differentiated skin cells is published.

And then what?

You will have an autologous stem cell line that you can use to produce tissues that are, immunologically speaking, identical to those in your body.  What should you do with them?  I would suggest you show them off at cocktail parties, brag about them on Facebook, and then destroy them with bleach and an autoclave.  In lieu of an autoclave a microwave would probably do just fine.

But I expect that at least some of you will try to follow a recipe to generate some sort of human tissue, or even to simply inject those cells in your own bodies, which will result in all kinds of crazy teratomas and other tumors.  To quote Harold Ramus, "that would be bad".  So don't do that.  Just because DIYStemCells are cool doesn't mean you should actually use them yourself.  But I know some of you will anyway.  That is the future of biological technologies, for better or worse.

The Economist Debate on the Fuel of the Future for Cars

Last week The Economist ran an online debate considering the motion "Biofuels, not electricity, will power the car of the future".  I was privileged to be invited as a guest contributor along with Tim Searchinger of Princeton University.  The two primary "speakers" were Alan Shaw of Codexis and Sidney Goodman of Automotive Alliances.  Here is my contribution to the debate, in which I basically rejected the false dichotomy of the motion (the first two 'graphs follow):

The future of transportation power sources will not be restricted to "either/or". Rather, over the coming decades, the nature of transportation fuel will be characterised by a growing diversity. The power sources for the cars of the future will be determined by the needs those cars address.

Those needs will be set for the market by a wide range of factors. Political and economic pressures are likely to require reducing greenhouse gas emissions and overall energy use per trip. Individuals behind the wheel will seek to minimise costs. But there is no single fuel that simultaneously satisfies the requirements of carbon neutrality, rapid refuelling, high-energy density for medium- to long-range driving and low cost.

I find it interesting that the voting came down so heavily in favor of electricity as the "fuel" of the future.  I suppose the feasibility of widespread electric cars depends on what you mean by "future".  Two substantial technology shifts will have to occur before electric cars displace those running on liquid fuels, both of which will require decades and trillions.

First, for the next several decades, no country, including the US, is likely to have sufficient electricity generating resources and power distribution infrustructure to convert large numbers of automobiles to electric power.  We need to install all kinds of new transmission lines around the country to pull this off.  And if we want the electricity to be carbon neutral, we need to install vast amounts of wind and solar generating capacity.  I know Stewart Brand is now arguing for nuclear power as "clean energy", but that still doesn't make sense to me for basic economic reasons. (Aside: at a party a few months ago, I got Lowell Wood to admit that nuclear power can't be economically viable unless the original funders go bankrupt and you can buy the physical plant on the cheap after all the initial investment has been wiped out.  Sweet business model.)

Second, the energy density of batteries is far below that of liquid hydrocarbons.  (See the Ragone chart included in my contribution to The Economist debate.)  Batteries are likely to close the gap over the coming years, but long distance driving will be the domain of liquid fuels for many years to come.  Yes, battery changing stations are an interesting option (as demonstrated by Better Place), but it will take vast investment to build a network of such stations sufficient to replace (or even compete with) liquid fuels.  Plugging in to the existing grid will require many hours to charge the batteries, if only because running sufficient current through most existing wires (and the cars themselves) to recharge car batteries rapidly would melt those wires.  Yes, yes -- nanothis and nanothat promise to enable rapid recharging of batteries.  Someday.  'Til then, don't bother me with science fiction.  And even if those batteries do show up in the proverbial "3 to 5 year" time frame, charging them rapidly would still melt most household power systems.

In the long run, I expect that electric cars will eventually replace those powered by liquid fuels.  But in the mean time, liquid fuels will continue to dominate our economy.

Stem_Cells@Home or DIYStemCells?

I'm in Cambridge, UK, and mostly on local time.  Mostly.  Spring is very pleasant here.

IMG_0115.JPG

Here are a couple of interesting things that I've come across recently.

The FDA is considering regulating autologous stem cells as prescription drugs.  These cells are removed from a patient, multiplied in culture, and then reintroduced at a site of injury.  The culture step, reportedly, gets the FDA all in a lather with the desire for control.  According to the author of a story at h+ magazine, this could drastically slow down adoption and use, and potentially relegate the the technology to large corporate interests.  The story, and an accompanying interview with a physician, argues that self-regulation of stem cell treatments as a medical practice (which the FDA is not chartered to regulate) is a far better choice.

If the FDA does go the route of asserting (or, rather, attempting to assert) its might, it suggests to me that once again the powers that be are not sufficiently in tune with the progress of technology.  To wit: here is Attila Chordash's homebrew procedure from MAKE for isolating placental stem cells (I met Attila a few years ago at SciFoo and have participated with him in some IFTF activities -- smart fellow).  News this past year has been full of various ways to produce induced pluripotent stem (iPS) cells, ranging from retroviral reprogramming, to drug-controlled lentiviruses, to plasmid-mediated reprogramming. Skin cells were turned into iPSs early in 2008 (here is an earlier summary at Nature Reports Stem Cells).  Last November, a paper in PNAS showed a single synthetic prophage containing 4 genes was sufficient to turn a mouse fibroblast into an iPS cell, and showed that the method could be used to generate human iPS cells from human keratinocytes.  Each of these steps is said to demonstrate an increase the controllability of the reprogramming, increase the uniformity of the resulting population of cells, and decrease the difficulty.

This is not to say that any step in the reprogramming is simple.  From personal experience I can testify that culturing even "stable" human cell lines can be challenging at times.  But, by definition, as published methods to reprogram cells are repeated and refined this will demonstrate a progression from iPS cell production as an art into a technology.  The plasmid-mediated programming, in particular, strikes me as a promising route to a widespread technology because it does not depend upon, or result in, integration of the plasmid into the host chromosome.  Moreover, it will be trivial to synthesize new genes for use in the plasmid as better recipes come along.  So how long before these cells will be used in therapies?

A recent review in Science by Gurdon and Melton identifies some interesting challenges:

The future value of reprogrammed cells is of two kinds. One is to create long-lasting cell lines from patients with genetic diseases, in order to test potentially useful drugs or other treatments. The other is to provide replacement cells for patients. To be therapeutically beneficial, replacement cells will probably need (i) to be provided in sufficient numbers; (ii) to carry out their function, even though they are not normally integrated into host tissues; and (iii) to be able to produce the correct amount of their product.

A human adult has about 1015 cells, and the liver contains about 1014 cells. To create this number of cells starting from a 10-4 success rate of deriving iPS cells from skin would require an enormous number of cell divisions in culture, although the prolonged culture of ES-like cells provides a valuable amplification step. However, many parts of the human body need a far smaller number of cells to improve function. An example is the human eye retina, in which only 105 cells could be of therapeutic benefit.

Will introduced cells be useful even if not "properly" integrated into the host? Most organs consist of a complex arrangement of several different cell types. The pancreas, for example, contains exocrine (acinar) cells, ductal cells, and at least four kinds of hormone-secreting cells in the endocrine islet. Replacement endocrine cells can provide useful therapeutic benefit even if not incorporated into the normal complex pancreas cell configuration. In some cases, introduced cells can have functionally beneficial effects, even if indirectly. It is not yet clear whether introduced cells will be correctly regulated to produce the desired amount of product.

There is obviously a great deal of science to do before iPS cells are used on a regular basis to produce therapies. Nonetheless, therapy is already beginning around the world.  Medical tourism to China for stem cell treatments is increasingly common, even for children.

Clearly, the technology is so promising that families are willing to go to considerable sacrifice to obtain treatment.  Which brings us back to the FDA and regulation.  I have to wonder what the Feds are thinking.  I would certainly agree with anyone who suggests that stem cells are a powerful technology, and that treatments should be safe.  But any regulatory or policy step that reduces access and slows progress in the US is simply going to send people overseas for treatment.  Then, as the technology becomes ever simpler to learn and use, a back-room market will open up in the States.  
 
So, I wonder, as the technology matures, how long before we get DIYStemCells, Stem_Cells@Home, or HomebrewStemCells?  As methods are published to harvest candidate cells and turn them into autologous iPS cells, how long will it be before athletes looking for an edge, the curious, and the truly ill, all start trying this for themselves?  I am by no means arguing that this is a good idea, and I strongly suspect that the better course is to ensure that people have access to the technology through physicians who know what they are doing.  But without that access, a black market, with all of the shadows and horrors envisioned by William Gibson and others, is inevitable.

Wouldn't it be simpler, and vastly safer, to make sure that everyone has access to skills and materials?  This seems like another arena in which pushing for an Open Biology makes a great deal more sense than the alternative.

H1N1 is a "rotten pot", plus the beginnings of vaccine plans

A ProMED mail from yesterday (Archive Number 20090430.1636) has some interesting tidbits.

First, following up on the confusion over the genetic origins of "H1N1 Influenza A", the group at Columbia states:

Preliminary analysis of the genome of the new H1N1 influenza A virus responsible for the current pandemic indicates that all genetic segments are related closest to those of common swine influenza viruses.

...Six segments of the virus are related to swine viruses from North America and the
other 2 (NA and M) from swine viruses isolated in Europe/Asia.

The North American ancestors are related to the multiple reassortants, H1N2 and H3N2 swine viruses isolated in North America since 1998 [2,3]. In particular, the swine H3N2 isolates from 1998 were a triple reassortment of human, swine and avian origin.

Therefore, this preliminary analysis suggests at least 2 swine ancestors to the current H1N1, one of them related to the triple reassortant viruses isolated in North America in 1998.

So, it's composed of all recent pig viruses, but displays some inheritance from human and avian strains from a decade ago.  It's a flu potpourri!  And here I intend the original French meaning of the word potpourri -- "rotten pot".

On the vaccine front, there is a mix of efforts.  It is unclear when a traditional vaccine might show up.  However, the ProMED mail does contain an excerpt of a Scientific American story that suggests Novavax is already working on a VLP synthetic vaccine, possibly confirming my earlier speculation.

On Pandemic Preparendness, Surveillance, and Surprise

After working with Bio-era for several years on pandemic preparedness, pathogen surveillance, and synthetic vaccines, a few things jumped out at me from ScienceInsider's interview with CDC Virologist Ruben Donis.

As part of the discussion on the origin of the present "H1N1 Influenza A", as we are now supposed to call it, Donis notes that "The amazing thing is the hemagglutinins we are seeing in this strain are a lonely branch that have been evolving somewhere and we didn't know about it."

Translation: Despite the increased surveillance since 2005, a key set of genes that are important components of the present virus(es) appeared out of nowhere, or, rather, appeared out of somewhere that the surveillance does not reach.  Must fix.  Immediately.

With respect to vaccine development, Donis suggests that "The virus doesn't grow very well in eggs. We hope the virus will improve [the] ability to grow in eggs so we can produce [a] vaccine very quickly so these secondary and tertiary cases can be controlled."  It is unclear at this point in the interview whether he is referring specifically to "H1N1 Influenza A", or to a larger group of viruses, or something else.  Assuming he means the present (almost pandemic) strain, it is interesting that somebody at CDC already knows the bug doesn't grow well in eggs.  It is also unclear what he means by "we hope the virus will improve [the] ablity to grow in eggs" -- perhaps he is referring to an effort to produce a vaccine via reverse genetics for production in eggs.  Either way, it suggests we may have to rely on newer technologies to produce vaccines (see my earlier posts on synthetic vaccines).

I have heard rumors that DARPA has a program up and running to turn out several million doses of synthetic vaccines (VLPs, primarily) in six weeks.  Here's hoping those are more than rumors.

The interview with Donis ends on a rather somber note:  Even though the flu season is ending in North America and Europe, we can't forget the rest of the planet: "The folks in Buenos Aires are in trouble. They're entering winter now."

This is a long, long way from being over.

More on the genetics of the H1N1 virus

Effect Measure has a nice post on the origin of genes in the present H1N1 strain making the rounds, and it adds some subtlety to the story I relayed a couple of days ago.

In short, the genome appears to be composed of pieces that have all be circulating in pigs for many years, yet some of those genes may have originally come from human and avian viruses.

I took a few minutes last night to add tags to most of my old posts about SARS, H5N1, vaccines, influenza, and infectious disease.  I also fixed a few links still broken from the ISP switch last year, including the SARS outbreak timeline in "Nature is Full of Surprises, and We Are Totally Unprepared".

Update:  Here is another good 2009 H1N1 Flu Outbreak map from Google.

Confusion over genetic origin of Mexican "Swine Flu" and assorted press nonesense.

There appears to be uncertainty over just which genes are in the H1N1 genome now causing illness.

(Update: Must read for anyone interested in the present situation: the CIDRAP Swine Influenza Overview.)

As of the evening of Tuesday, 28 April, CNN is reporting that:

The new virus has genes from North American swine influenza, avian influenza, human influenza and a form of swine influenza normally found in Asia and Europe, said Nancy Cox, chief of the CDC's Influenza Division.

However, today's ProMED mail contained a the following exchange.

From Professor Roger Morris, at Massey University, New Zealand, a whole bunch of really good questions:

For those of us who are involved in international work on influenza epidemiology and control and responding to the many media enquiries, there is a very large information gap in relation to diagnosis and epidemiology of the Mexican influenza. What is known of the genetic structure of this virus? It has been called a swine flu, but no evidence has been put forward to allow this statement to be evaluated. I have received information that it is a reassortant, which has genetic components from 4 different sources, but nothing official has been released on this. Where does it fit phylogenetically? Is there any genetic variation of significance among the isolates investigated? Would this help to explain the difference in severity of disease between Mexico and other countries?

It is also stated that it should be diagnosed by RT-PCR, without clarifying which PCR. I have received information that the standard PCR for H1 does not reliably detect this virus. Is this true? What is an appropriate series of diagnostic steps for samples from suspect cases? Could we have an authoritative statement on these issues from one of the laboratories, which has been working with the virus?

In response, here is Professor Paul Rabadan, of Columbia University College of Physicians and Surgeons, who is digging into the flu genome sequences filed at NCBI and finds that the sequence appears to be solely of swine (swinian?) origin:

In relation to the questions posed by Prof. Morris: My group and I are analyzing the recent sequences from the isolates in Texas and California of swine H1N1 deposited in National Center for Biotechnology Information (NCBI) (A/California/ 04/2009(H1N1), A/California/05/2009(H1N1), A/California/ 06/2009(H1N1), A/California/07/2009(H1N1), A/California/09/2009(H1N1), A/Texas/04/2009(H1N1) and A/Texas/05/2009(H1N1).

The preliminary analysis using all the sequences in public databases (NCBI) suggests that all segments are of swine origin. NA and MP seem related to Asian/European swine and the rest to North American swine (H1N2 and H3N2 swine viruses isolated since 1998). There is also interesting substratification between these groups, suggesting a multiple reassortment.

We are puzzled about sources of information that affirm that the virus is a reassortment of avian, human and swine viruses. It is true that the H3N2 swine virus from 1998 and 1999 is a triple reassortant, but all the related isolates are found since then in swine.

In lay English: the virus is composed of pieces of other viruses found in pigs.  While the structure of the genome is curious, in that it appears the different viruses exchanged chromosomes multiple times, there isn't any sign that the present genome of concern contains elements of avian or human flu viruses.

(Update: I just stumbled over a 21 April CDC briefing that describes the genomes of H1N1 viruses in pediatric cases in California as entirely of swine origin.)

So it isn't at all clear why the press (and government officials) keep repeating the assertion that the new virus is some sort of amazing Frankenstein strain.  The message containing Professor Rabadan's comments also notes that a mess of new sequences from clinical isolates were filed today in the GISAID database.  Analysis of those sequences should help clarify the origin -- or at least the composition of the genome -- of the virus in the coming days.

The press also continues to bray about flies as the vector, when there is no evidence I can find in any literature, anywhere, that suggests flies have ever been associated with transmitting the flu.  If this particular bug did figure out how to hitch a ride of flies, that would be some seriously scary evolutionary juju.  Intelligent design, even.  We would all be in deep trouble.  But, as there is no evidence to support these assertions other than repeating what other reporters are saying, my recommendation to all you in the press would be simply this: STOP.

Similarly, the notion that at this early date anyone could possibly have identified the index case ("Patient 0") as a young boy in some village in Mexico is -- let me choose my words very carefully here -- COMPLETE PIGSHIT.  With so little molecular forensics done on the virus, and no real map of who is actually sick, who has been sick, nor when or where they were sick, publishing the name of an innocent four-year old boy based on cribbing from some other reporter's story is the height of irresponsible journalism.  Where the fuck are the editors?

(Update: The New York Times is still repeating this nonesense: "...The Mexican government has identified a young boy as the first person in the country infected with swine flu...".  Waaay down in the story it acknowledges that the village the boy is from "may not, in the end, be found to be the source of anything" and then goes on to describe earlier potential cases. Oy.)

Perhaps reporters should try a little, oh, I don't know, reporting.  Visit ProMED mail.  Check out CIDRAP and Effect Measure.  Stop reading what other reporters write, and think for yourseves.  We will all be better off.