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.

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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.

H1N1 Influenza coverage

Well, it looks like we got surprised.  Just like we, um, expectedTo be surprised, that is.

It's been quite a while since I wrote anything about the flu, but I suppose I should start keeping track of interesting new developments.

We should consider the clock started on vaccine development.  Various reports suggest that Baxter is already at work at the request of the Mexican government.  News outlets are being very careless, throwing around phrases like "vaccines are at least six months away", when it would surprise me if anything became available in less than nine months.  I expect it to be more like 12-18 months, but I really, truly, hope I am wrong about this.  All of a sudden we are doing a real-world test of our preparedness.

There is excellent coverage, as usual, over at EffectMeasure.  Other reporting is sort of spotty.  I keep seeing stories (Wired, CNN, even the NYT) reporting that the CDC says vomiting and diarrhea are symptoms of the flu, when what the CDC says is that "some people report" those symptoms for the flu.  Usually GI tract symptoms like that are due to noroviruses (think cruise ships), not influenza viruses.  But I suppose we could be seeing something new.

I just heard a report from the BBC suggesting that Mexico thinks as many as 2000 people have been infected, with Mexico's health minister putting the death toll at 149.  That would put the fatality rate at 7.5%, which would be extremely high for the flu.  It is too early to say whether those numbers are realistic or not, especially since Mexico will have difficulty making positive molecular diagnoses.  I would expect a retrospective analysis of this outbreak to determine that many, many more people have been exposed and infected than presently reported.  It is certainly confusing why all the deaths have thus far been confined to Mexico.

It seems that cases are already spread across the world.  Here is a Google Maps version of suspected and confirmed cases, which looks to be maintained by Henry Niman.  Good show Dr. Niman, even though I haven't always seen eye to eye with you on your ideas about the flu and SARS.  Niman seems to be maintaining a bunch of other such maps, which are worth checking out, including H5N1 in Egypt and ... "SARS 2009" -- WTF!!!

*shudder*

Back to H1N1: According to this ProMED summary, Israel is taking the most important step it can in preparing:

Israel renames unkosher swine flu.
Israel's health minister updates a nervous public about the swine flu 
epidemic - and starts by renaming it Mexican flu.

Perhaps my slight turn to appreciating black humor here is that I just don't see that things have improved very much since 2005.  In mid-February of this year, I sat around a table in DC with a bunch of people who had been called together to discuss biopreparedness, whether for natural or artificial threats.  The person convening the meeting suggested that basically everyone who deeply cared about the issue in DC was in the room, and it was a disturbingly small group.

Also disturbing was what those people reported about their experiences in trying to prepare the US for the inevitable appearance of biothreats.  The news wasn't encouraging.  Another anecdote for context -- in 2005 I had a conversation with the head of Asian operations for one of the two remaining international express shipping companies.  At that time, his company hadn't given much thought to the flu -- this was before all the hullaballoo -- and he suggested should H5N1 become a problem that the company would simply stop flying.  An executive from a major disposable syringe manufacturer then suggested there would be no way to keep up with demand if that shipping stopped.  I went on to write here, and elsewhere, about what might happen to not just our economy, but also our R&D efforts, if plastic labware and rubber gloves made in Asia were stuck there.  I can report that, as of February this year, there are at least a few stockpiles of critical supplies here in the States, but that the academics, state, and federal officials around that table in DC were far less than sanguine about our state of preparedness.  One professor, who was running an ongoing assessment of his state's preparedness, suggested that they were still having trouble getting the basic data they needed on the available stock of consumables in hospitals.

I have been concentrating on other topics for the last eighteen months or so, and so I raised my hand to express my incredulous dismay that things haven't improved in 4 years.  That generated an interesting response.  About half the room assured me it was okay, and the other half assured me my dismay was entirely warranted.  Great.

Thus my slightly foul mood as a new potential threat is rapidly finding its way around the globe.  That and the fact that I am about to climb into an airplane bound for the UK -- eight hours in a closed environment with hundreds of international travelers at the beginning of a potential epidemic.  Oh, joy.

Where's my Tamiflu?

A few notes from Nature Biotech

I am catching up on past issues of Nature Biotech.  Here are a few things that caught my eye:

(Feb 09) Cuba is launching a domestically produced GM corn.  The strain (which looks from the name to contain Bt) is to be used in animal feed.  Another sign that developing countries view biotech as important national initiatives, and that they can push the technology on their own.

(Feb 09) Researchers in Belgium got fed up with efforts to get their field trial for GM poplars approved in country, and are taking the trial to the Netherlands.  So much for uniformly applying laws on planting GM crops in Europe.  (Mar 09) Local environment ministers voted to overturn the European Commission's initiative to force member states to lift national bans.

(April 09) Malaysia has dropped several billions of dollars on biotech as part of their stimulus package.  More on this when I dig into it.

The Origin of Moore's Law and What it May (Not) Teach Us About Biological Technologies

While writing a proposal for a new project, I've had occasion to dig back into Moore's Law and its origins.  I wonder, now, whether I peeled back enough of the layers of the phenomenon in my book.  We so often hear about how more powerful computers are changing everything.  Usually the progress demonstrated by the semiconductor industry (and now, more generally, IT) is described as the result of some sort of technological determinism instead of as the result of a bunch of choices -- by people -- that produce the world we live in.  This is on my mind as I continue to ponder the recent failure of Codon Devices as a commercial enterprise.  In any event, here are a few notes and resources that I found compelling as I went back to reexamine Moore's Law.

What is Moore's Law?

First up is a 2003 article from Ars Technica that does a very nice job of explaining the why's and wherefore's: "Understanding Moore's Law".  The crispest statement within the original 1965 paper is "The number of transistors per chip that yields the minimum cost per transistor has increased at a rate of roughly a factor of two per year."  At it's very origins, Moore's Law emerged from a statement about cost, and economics, rather than strictly about technology.

I like this summary from the Ars Technica piece quite a lot:

Ultimately, the number of transistors per chip that makes up the low point of any year's curve is a combination of a few major factors (in order of decreasing impact):

  1. The maximum number of transistors per square inch, (or, alternately put, the size of the smallest transistor that our equipment can etch),
  2. The size of the wafer
  3. The average number of defects per square inch,
  4. The costs associated with producing multiple components (i.e. packaging costs, the costs of integrating multiple components onto a PCB, etc.)

In other words, it's complicated.  Notably, the article does not touch on any market-associated factors, such as demand and the financing of new fabs.

The Wiki on Moore's Law has some good information, but isn't very nuanced.

Next, here an excerpt from an interview Moore did with Charlie Rose in 2005:

Charlie Rose:     ...It is said, and tell me if it's right, that this was part of the assumptions built into the way Intel made it's projections. And therefore, because Intel did that, everybody else in the Silicon Valley, everybody else in the business did the same thing. So it achieved a power that was pervasive.

Gordon Moore:   That's true. It happened fairly gradually. It was generally recognized that these things were growing exponentially like that. Even the Semiconductor Industry Association put out a roadmap for the technology for the industry that took into account these exponential growths to see what research had to be done to make sure we could stay on that curve. So it's kind of become a self-fulfilling prophecy.

Semiconductor technology has the peculiar characteristic that the next generation always makes things higher performance and cheaper - both. So if you're a generation behind the leading edge technology, you have both a cost disadvantage and a performance disadvantage. So it's a very non-competitive situation. So the companies all recognize they have to stay on this curve or get a little ahead of it.

Keeping up with 'the Law' is as much about the business model of the semiconductor industry as about anything else.  Growth for the sake of growth is an axiom of western capitalism, but it is actually a fundamental requirement for chipmakers.  Because the cost per transistor is expected to fall exponentially over time, you have to produce exponentially more transistors to maintain your margins and satisfy your investors.  Therefore, Intel set growth as a primary goal early on.  Everyone else had to follow, or be left by the wayside.  The following is from the recent Briefing in The Economist on the semiconductor industry:

...Even the biggest chipmakers must keep expanding. Intel todayaccounts for 82% of global microprocessor revenue and has annual revenues of $37.6 billion because it understood this long ago. In the early 1980s, when Intel was a $700m company--pretty big for the time--Andy Grove, once Intel's boss, notorious for his paranoia, was not satisfied. "He would run around and tell everybody that we have to get to $1 billion," recalls Andy Bryant, the firm's chief administrative officer. "He knew that you had to have a certain size to stay in business."

Grow, grow, grow

Intel still appears to stick to this mantra, and is using the crisis to outgrow its competitors. In February Paul Otellini, its chief executive, said it would speed up plans to move many of its fabs to a new, 32-nanometre process at a cost of $7 billion over the next two years. This, he said, would preserve about 7,000 high-wage jobs in America. The investment (as well as Nehalem, Intel's new superfast chip for servers, which was released on March 30th) will also make life even harder for AMD, Intel's biggest remaining rival in the market for PC-type processors.

AMD got out of the atoms business earlier this year by selling its fab operations to a sovereign wealth fund run by Abu Dhabi.  We shall see how they fare as a bits-only design firm, having sacrificed their ability to themselves push (and rely on) scale.

Where is Moore's Law Taking Us?

Here are a few other tidbits I found interesting:

Re the oft-forecast end of Moore's Law, here is Michael Kanellos at CNET grinning through his prose: "In a bit of magazine performance art, Red Herring ran a cover story on the death of Moore's Law in February--and subsequently went out of business."

And here is somebody's term paper (no disrespect there -- it is actually quite good, and is archived at Microsoft Research) quoting an interview with Carver Mead:

Carver Mead (now Gordon and Betty Moore Professor of Engineering and Applied Science at Caltech) states that Moore's Law "is really about people's belief system, it's not a law of physics, it's about human belief, and when people believe in something, they'll put energy behind it to make it come to pass." Mead offers a retrospective, yet philosophical explanation of how Moore's Law has been reinforced within the semiconductor community through "living it":

After it's [Moore's Law] happened long enough, people begin to talk about it in retrospect, and in retrospect it's really a curve that goes through some points and so it looks like a physical law and people talk about it that way. But actually if you're living it, which I am, then it doesn't feel like a physical law. It's really a thing about human activity, it's about vision, it's about what you're allowed to believe. Because people are really limited by their beliefs, they limit themselves by what they allow themselves to believe what is possible. So here's an example where Gordon [Moore], when he made this observation early on, he really gave us permission to believe that it would keep going. And so some of us went off and did some calculations about it and said, 'Yes, it can keep going'. And that then gave other people permission to believe it could keep going. And [after believing it] for the last two or three generations, 'maybe I can believe it for a couple more, even though I can't see how to get there'. . . The wonderful thing about [Moore's Law] is that it is not a static law, it forces everyone to live in a dynamic, evolving world.

So the actual pace of Moore's Law is about expectations, human behavior, and, not least, economics, but has relatively little to do with the cutting edge of technology or with technological limits.  Moore's Law as encapsulated by The Economist is about the scale necessary to stay alive in the semiconductor manufacturing business.  To bring this back to biological technologies, what does Moore's Law teach us about playing with DNA and proteins?  Peeling back the veneer of technological determinism enables us (forces us?) to examine how we got where we are today. 

A Few Meandering Thoughts About Biology

Intel makes chips because customers buy chips.  According to The Economist, a new chip fab now costs north of $6 billion.  Similarly, companies make stuff out of, and using, biology because people buy that stuff.  But nothing in biology, and certainly not a manufacturing plant, costs $6 billion.

Even a blockbuster drug, which could bring revenues in the range of $50-100 billion during its commercial lifetime, costs less than $1 billion to develop.  Scale wins in drug manufacturing because drugs require lots of testing, and require verifiable quality control during manufacturing, which costs serious money.

Scale wins in farming because you need...a farm.  Okay, that one is pretty obvious.  Commodities have low margins, and unless you can hitch your wagon to "eat local" or "organic" labels, you need scale (volume) to compete and survive.

But otherwise, it isn't obvious that there are substantial barriers to participating in the bio-economy.  Recalling that this is a hypothesis rather than an assertion, I'll venture back into biofuels to make more progress here.

Scale wins in the oil business because petroleum costs serious money to extract from the ground, because the costs of transporting that oil are reduced by playing a surface-to-volume game, and because thermodynamics dictates that big refineries are more efficient refineries.  It's all about "steel in the ground", as the oil executives say -- and in the deserts of the Middle East, and in the Straights of Malacca, etc.  But here is something interesting to ponder: oil production may have maxed out at about 90 million barrels a day (see this 2007 article in the FT, "Total chief warns on oil output").  There may be lots of oil in the ground around the world, but our ability to move it to market may be limited.  Last year's report from Bio-era, "The Big Squeeze", observed that since about 2006, the petroleum market has in fact relied on biofuels to supply volumes above the ~90 million per day mark.  This leads to an important consequence for distributed biofuel production that only recently penetrated my thick skull.

Below the 90 million barrel threshold, oil prices fall because supply will generally exceed demand (modulo games played by OPEC, Hugo Chavez, and speculators).  In that environment, biofuels have to compete against the scale of the petroleum markets, and margins on biofuels get squeezed as the price of oil falls.  However, above the 90 million per day threshold, prices start to rise rapidly (perhaps contributing to the recent spike, in addition to the actions of speculators).  In that environment, biofuels are competing not with petroleum, but with other biofuels.  What I mean is that large-scale biofuels operations may have an advantage when oil prices are low because large-scale producers -- particularly those making first-generation biofuels, like corn-based ethanol, that require lots of energy input -- can eke out a bit more margin through surface to volume issues and thermodynamics.  But as prices rise, both the energy to make those fuels and the energy to move those fuels to market get more expensive.  When the price of oil is high, smaller scale producers -- particularly those with lower capital requirements, as might come with direct production of fuels in microbes -- gain an advantage because they can be more flexible and have lower transportation costs (being closer to the consumer).  In this price-volume regime, petroleum production is maxed out and small scale biofuels producers are competing against other biofuels producers since they are the only source of additional supply (for materials, as well as fuels).

This is getting a bit far from Moore's Law -- the section heading does contain the phrase "meandering thoughts" -- I'll try to bring it back.  Whatever the origin of the trends, biological technologies appear to be the same sort of exponential driver for the economy as are semiconductors.  Chips, software, DNA sequencing and synthesis: all are infrastructure that contribute to increases in productivity and capability further along the value chain in the economy.  The cost of production for chips (especially the capital required for a fab) is rising.  The cost of production for biology is falling (even if that progress is uneven, as I observed in the post about Codon Devices).&nb sp; It is generally becoming harder to participate in the chip business, and it is generally becoming easier to participate in the biology business.  Paraphrasing Carver Mead, Moore's Law became an organizing principal of an industry, and a driver of our economy, through human behavior rather than through technological predestination.  Biology, too, will only become a truly powerful and influential technology through human choices to develop and deploy that technology.  But access to both design tools and working systems will be much more distributed in biology than in hardware.  It is another matter whether we can learn to use synthetic biological systems to improve the human condition to the extent we have through relying on Moore's Law.