synthesis

Harry Potter and The Future of Nature

2013-05-21T17:38:50Z

How will Synthetic Biology and Conservation Shape the Future of Nature? Last month I was privileged to take part in a meeting organized by The Wildlife Conservation Society to consider that question. Here is the framing paper (PDF), of which I am a co-author. There will be a follow-up paper in the coming months. I am still mulling over what I think happened during the meeting, and below are a few observations that I have managed to settle on so far. Others have written their own accounts. Here is a summary from Julie Gould, riffing on an offer that Paul Freemont made to conservation biologists at the close of the meeting, "The Open Door". Ed Gillespie has a lovely, must-read take on Pandora's Box, cane toads, and Emily Dickenson, "Hope is the thing with feathers". Cristian Samper, the new head of the Wildlife Conservation Society was ultimately quite enthusiastic: Jim Thomas of ETC, unsurprisingly, not so much.

The meeting venue was movie set-like Cambridge. My journey took me through King's Cross, with its requisite mock-up of a luggage trolley passing through the wall at platform nine and three-quarters. So I am tempted to style parts of the meeting as a confrontation between a boyish protagonist trying to save the world and He Who Must Not Be Named. But my experience at the meeting was that not everyone was able to laugh at a little tension-relieving humor, or even to recognize that humor. Thus the title of this post is as much as I will give in temptation.

How Can SB and CB Collaborate?

I'll start with an opportunity that emerged during the week, exactly the sort of thing you hope would come from introducing two disciplines to each other. What if synthetic biology could be used as a tool to aid in conservation efforts, say to buttress biodiversity against threats? If the ongoing, astonishing loss of species were an insufficient motivation to think about this possibility, now some species that humans explicitly rely upon economically are under threat. Synthetic biology might - might! - be able to offer help in the form of engineering species to be more robust in the face of a changing environment, such as enabling corals to cope with increases in water temperature and acidity, or it perhaps via intervening in a host-prey relationship, such as that between bats and white-nose disease or between bees and their mites and viruses.

The first thing to say here is that if the plight of various species can be improved through changes in human behavior then we should by all means work toward that end. The simpler solution is usually the better solution. For example, it might be a good idea to stop using those pesticides and antibiotics that appear to create more problems than they solve when introduced into the environment. Moreover, at the level of the environment and the economy, technological fixes are probably best reserved until we try changes in human behavior. After all, we've mucked up such fixes quite a few times already. (All together now: "Cane Toad Blues".) But what if the damage is too far along and cannot be addressed by changes in behavior? We should at least consider the possibility that a technological fix might be worth a go, if for no other reason that to figure out how to create a back up plan. Given the time scales involved in manipulating complex organisms, exploring the option of a back-up plan means getting started early. It also means thoughtfully considering which interventions would be most appropriate and urgent, where part of the evaluation should probably involve asking whether changes in human behavior are likely to have any effect. In some cases, a technical solution is likely to be our only chance.

First up: corals.

We heard from Stanford's Steve Palumbi on work to understand the effects of climate change on corals in the South Pacific. Temperature and acidity - two parameters already set on long term changes - are already affecting coral health around the globe. But it turns out that in the lab some corals can handle remarkably difficult environmental conditions. What if we could isolate the relevant genetic circuits and, if necessary, transplant them into other species, or turn them on if they are already widespread? My understanding of Professor Palumbi's talk is that it is not yet clear why some corals have the pathway turned on and some do not. So, first up, a bunch of genetics, molecular biology, and field biology to figure out why the corals do what they do. After that, if necessary, it seems that it would be worth exploring whether other coral species can be modified to use the relevant pathways. Corals are immensely important for the health of both natural ecosystems and human economies; we should have a back-up plan, and synthetic biology could certainly contribute.

Next up: bats.

Bats are unsung partners of human agriculture, and they contribute an estimated $23 billion annually to U.S. farmers by eating insects and pollinating various plants. Here is nice summary article from The Atlantic by Stephanie Gruner Buckely on the impact upon North American bats of white nose syndrome. The syndrome, caused by a fungus evidently imported from Europe, has already killed so many bats that we may see an impact on agriculture as soon as this year. European bats are resistant to the fungus, so one option would be to try to introduce the appropriate genes into North American bats via standard breeding. However, bats breed very slowly, usually only having one pup a year, and only 5 or so pups in a lifetime. Given the mortality rate due to white nose syndrome, this suggests breeding is probably too slow to be useful in conservation efforts. What if synthetic biology could be used to intervene in some way, either to directly attack the non-native fungus or to interfere with its attack on bats. Obviously this would be a hard problem to take on, but both biodiversity and human welfare would be improved by making progress here.

And now: bees.

If you eat, you rely on honeybees. Due to a variety of causes, bee populations have fallen to the point where food crops are in jeopardy. Entomologist Dennis vanEngelstorp, quoted in Wired, warns "We're getting closer and closer to the point where we don't have enough bees in this country to meet pollination demands. If we want to grow fruits and nuts and berries, this is important. One in every three bites [of food consumed in the U.S.] is directly or indirectly pollinated by bees." Have a look at the Wired article for a summary of the constellation of causes of Colony Collapse Disorder, or CCD -- they are multifold and interlocking. Obviously, the first thing to do is to stop making the problem worse; Europe has banned a class of pesticide that is exceptionally hard on honeybees, though the various sides in this debate continue to argue about whether that will make any difference. This change in human behavior may have some impact, but most experts agree we need to do more. Efforts are underway to breed bees that are resistant to both pesticides and to particular mites that prey on bees and that transmit viruses between bees. Applying synthetic biology here might be the hardest task of all, given the complexity of the problem. Should synthetic biologists focus on boosting apian immune systems? Should they focus on the mite? Apian viruses? It sounds very difficult. But with such a large fraction of our food supply dependent upon healthy bees, it also seems pretty clear that we should be working on all fronts to sort out potential solutions.

A Bit of Good News

Finally, a problem synthetic biologists are already working to solve: malaria. The meeting was fortunate to hear directly from Jay Keasling. Keasling presented progress on a variety of fronts, but the most striking was his announcement that Sanofi-Aventis has produced substantially more artemisinin this year than planned, marking real progress in producing the best malaria drug extant using synthetic biology rather than by purifying it from plants. Moreover, he announced that Sanofi and OneWorldHealth are likely to take over the entire world production of artemisinin. The original funding deal between The Gates Foundation, OneWorldHealth, Amyris, and Sanofi required selling at cost. The collaboration has worked very hard at bringing the price down, and now it appears that they can simply outcompete the for-profit pricing monopoly.

The stated goal of this effort is to reduce the cost of malaria drugs and provide inexpensive cures to the many millions of people who suffer from malaria annually. Currently, the global supply fluctuates, as, consequently, do prices, which are often well above what those afflicted can pay. A stable, high volume source of the drug would reduce prices and also reduce the ability of middle-men to sell doctored, diluted, or mis-formulated artemisinin, all of which are contributing to a rise of resistant pathogens.

There is a potential downside to this project. If Sanofi and OneWorldHealth do corner the market on artemisinin, then farmers who currently grow artemisia will no longer have that option, at least for supplying the artemisinin market. That might be a bad thing, so we should at least ask the question of whether the world is a better place with artemisinin production done in vats or derived from plants. This question can be broken into two pieces: 1) what is best for the farmers? and 2) what is best for malaria sufferers? It turns out these questions have the same answer.

There is no question that people who suffer from malaria will be better off with artemisinin produced in yeast by Sanofi. Malaria is a debilitating disease that causes pain, potentially death, and economic hardship. The best estimates are that countries in which malaria is endemic suffer a hit to GDP growth of 1.3% annually compared to non-malarious countries. Over just a few years this yearly penalty swamps all the foreign aid those countries receive; I've previously argued that eliminating malaria would be the biggest humanitarian achievement in history and would make the world a much safer place. Farmers in malarious countries are the worst hit, because the disease prevents them from getting into the fields to work. I clashed in public over this with Jim Thomas around our respective testimonies in front of the Presidential Bioethics Commission a couple of years ago. Quoting myself briefly from the relevant blog post,

The human cost of not producing inexpensive artemisinin in vats is astronomical. If reducing the burden of malaria around the world on almost 2 billion people might harm "a few thousand" farmers, then we should make sure those farmers can make a living growing some other crop. We can solve both problems. ...Just one year of 1.3% GDP growth recovered by reducing (eliminating?) the impact of malaria would more than offset paying wormwood farmers to grow something else. There is really no argument to do anything else.

For a bit more background on artemisinin supply and pricing, and upon the apparent cartel in control of pricing both the drug and the crop, see this piece in Nature last month by Mark Peplow. I was surprised to learn that that the price of artemisia is set by a small group that controls production of the drug. This group, unsurprisingly, is unhappy that they may lose control of the market for artemisinin to a non-profit coalition whose goal is to eliminate the disease. Have a look at the chart titled "The Cost of Progress", which reveals substantial price fluctuations, to which I will return below.

Mr. Thomas responded to Keasling's announcement in Cambridge with a broadside in the Guardian UK against Keasling and synthetic biology more generally. Mr. Thomas is always quick to shout "What about the farmers?" Yet he is rather less apt to offer actual analysis of what farmers actually gain, or lose, by planting artemisia.

The core of the problem for farmers is in that chart from Nature, which shows that artemisinin has fluctuated in price by a factor of 3 over the last decade. Those fluctuations are bad for both farmers and malaria sufferers; farmers have a hard time knowing whether it makes economic sense to plant artemisia, which subsequently means shortages if farmers don't plant enough. Shortages mean price spikes, which causes more farmers to plant, which results in oversupply, which causes the price to plunge, etc. You'll notice that Mr. Thomas asserts that farmers know best, but he never himself descends to the level of looking at actual numbers, and whether farmers benefit by growing artemisia. The numbers are quite revealing.

Eyeballing "The Cost of Progress" chart, it looks like artemisia has been below the $400/kg level for about half the last 10 years. To be honest, there isn't enough data on the chart to make firm conclusions, but it does look like the most stable price level is around $350/kg, with rapid and large price spikes up to about $1000/kg. Farmers who time their planting right will probably do well; those who are less lucky will make much less on the crop. So it goes with all farming, unfortunately, as I am sure Mr. Thomas would agree.

During his talk, Keasling put up a chart I hadn't seen before, which showed predicted farmer revenues for a variety of crops. The chart is below; it makes clear that farmers will have substantially higher revenues planting crops other than artemisia at prices at or below $400/kg.

The Strange Arguments Against Microbial Production of Malaria Drugs

Mr. Thomas' response in the Guardian to rational arguments and actual data was a glib accusation that Keasling is dismissing the welfare of farmers with "Let them plant potatoes". This is actually quite clever and witty, but not funny in the slightest when you look at the numbers. Thomas worries that farmers in African and Asia will suffer unduly from a shift away from artemisia to yeast. But here is the problem: those farmers are already suffering -- from malaria. Digging deeper, it becomes clear that Mr. Thomas is bafflingly joining the pricing cartel in arguing against the farmers' best interests.

A brief examination of the latest world malaria map shows that the most intense malaria hot spots are in Africa and Asia, with South America not far behind (here is the interactive CDC version). Artemisia is primarily grown in Africa and Asia. That is, farmers most at risk of contracting malaria only benefit economically when there is a shortage of artemisinin, the risk of which is maintained by leaving artemisia production in the hands of farmers. Planting sufficient quantities of artemisia to meet demand means prices that are not economically viable for the farmer. There are some time lags here due to growing and processing the crop into the drug, but the upshot is that the only way farmers make more money planting artemisia than other crops is when there is a shortage. This is a deadly paradox, and its existence has only one beneficiary: the artemisinin pricing cartel. But we can now eliminate the paradox. It is imperative for us to do so.

Once you look at the numbers there is no argument Mr. Thomas, or anyone else, can make that we should do anything but brew artemisinin in vats and bring the price as low as possible.

I had previously made the macro-scale economic arguments about humanitarian impacts economic growth. Malarious countries, and all the farmers in them, would benefit tremendously by a 1.3% annual increase in GDP. But I only realized while writing this post that the micro-scale argument gives the same answer: the farmers most at risk from malaria only make money growing artemisia when there is a shortage of the drug, which is when they are most likely to be affected by the disease.

I get along quite well in person with Mr. Thomas, but I have long been baffled by his arguments about artemisinin. I heartily support his aims of protecting the rights of farmers and taking care of the land. We should strive to do the right thing, except when analysis reveals it to be the wrong thing. Since I only just understood the inverse relationship between artemisinin pricing and the availability of the drug to the very farmers growing artemisia, I am certain Mr. Thomas has not had the opportunity to consider the facts and think through the problem so that he might come to the same conclusion. I invite him to do so.

How Competition Improves DNA Sequencing

2013-04-23T21:36:22Z

The technology that enables reading DNA is changing very quickly. I've chronicled how price and productivity are each improving in a previous post; here I want to try to get at how the diversity of companies and technologies is contributing to that improvement.

As I wrote previously, all hell is breaking loose in sequencing, which is great for the user. Prices are falling and the capabilities of sequencing instruments are skyrocketing. From an analytical perspective, the diversity of platforms is a blessing and a curse. There is a great deal more data than just a few years ago, but it has become quite difficult to directly compare instruments that produce different qualities of DNA sequence, produce different read lengths, and have widely different throughputs.

I have worked for many years to come up with intuitive metrics to aid in understanding how technology is changing. Price and productivity in reading and writing DNA are pretty straightforward. My original paper on this topic (PDF) also looked at the various components of determining protein structures, which, given the many different quantifiable tasks involved, turned out to be a nice way to encapsulate a higher level look at rates of change.

In 2007, with the publication of bio-era's Genome Synthesis and Design Futures, I tried to get at how improvements in instrumentation were moving us toward sequencing whole genomes. The two axes of the relevant plot were 1) read length -- the length of each contiguous string of bases read by an instrument, critical to accurate assembly of genomes or chromosomes that can be hundreds of millions of bases long -- and 2) the daily throughput per instrument -- how much total DNA each instrument could read. If you have enough long reads you can use this information as a map to assemble many shorter reads into the contiguous sequence.

Because there weren't very many models of commercially available sequencers in 2007, the original plot didn't have a lot of data on it (the red squares and blue circles below). But the plot did show something interesting, which was that two general kinds of instruments were emerging at that time: those that produced long reads but had relatively limited throughput, and those that produced short reads but could process enormous amounts of sequence per day. The blue dots below were data from my original paper, and the red squares were derived from a Science news article in 2006 that looked at instruments said to be emerging over the next year or so.

I have now pulled performance estimates out of several papers assessing instruments currently on the market and added them to the plot (purple triangles). The two groupings present in 2007 are still roughly extant, though the edges are blurring a bit. (As with the price and productivity figures, I will publish a full bibliography in a paper later this year. For now, this blog post serves as the primary citation for the figure below.)

I am still trying to sort out the best way to represent the data (I am open to suggestions about how do it better). At this point, it is pretty clear that the two major axes are insufficient to truly understand what is going on, so I have attempted to add some information regarding the release schedules of new instruments. Very roughly, we went from a small number of first generation instruments in 2003 to a few more real instruments in 2006 that performed a little better in some regards, plus a few promised instruments that didn't work out for one reason or another. However, starting in about 2010, we began to see seriously improved instruments being released on an increasingly rapid schedule. This improvement is the result of competition not just between firms, but also between technologies. In addition, some of what we are seeing is the emergence of instruments that have niches; long reads but medium throughput, short reads but extraordinary throughput -- combine these two capabilities and you have the ability to crank out de novo sequences at pretty remarkable rate. (For reference, the synthetic chromosome Venter et al published a few years ago was about one million bases; human chromosomes are in the range of 60 to 250 million bases.)

And now something even more interesting is going on. Because platforms like PacBio and IonTorrent can upgrade internal components used in the actual sequencing, where those components include hardware, software, and wetware, revisions can result in stunning performance improvements. Below is a plot with all the same data as above, with the addition of one revision from PacBio. It's true that the throughput per instrument didn't change so much, but such long read lengths mean you can process less DNA and still rapidly produce high resolution sequence, potentially over megabases (modulo error rates, about which there seems to be some vigorous discussion). This is not to say that PacBio makes the best overall instrument, nor that the company will be commercially viable, but rather that the competitive environment is producing change at an extraordinary rate.

If I now take the same plot as above and add a single (putative) MinION nanopore sequencer from Oxford Nanopore (where I have used their performance claims from public presentations; note the question mark on the date), the world again shifts quite dramatically. Oxford also claims they will ship GridION instruments that essentially consist of racks of MinIONs, but I have not even tried to guess at the performance of that beast. The resulting sequencing power will alter the shape of the commercial sequencing landscape. Illumina and Life are not sitting still, of course, but have their own next generation instruments in development. Jens Gundlach's (PDF) team at the University of Washington has demonstrated a nanopore that is argued to be better than the one Oxford uses, and I understand commercialization is proceeding rapidly, though of course Oxford won't be sitting still either.

One take home message from this, which is highlighted by taking the time to plot this data, is that over the next few years sequencing will become highly accurate, fast, and commonplace. With the caveat that it is difficult to predict the future, continued competition will result in continued price decreases.

A more speculative take home emerges if you consider the implications of the MinION. That device is described as a disposable USB sequencer. If it -- or anything else like it -- works as promised, then some centralized sequencing operations might soon reach the end of their lives. There are, of course, different kinds of sequencing operations. If I read the tea leaves correctly, Illumina just reported that its clinical sequencing operations brought in about as much revenue as their other operations combined, including instrument sales. That's interesting, because it points to two kinds of revenue: sales of boxes and reagents that enable other people to sequence, and certified service operations that provide clinically relevant sequence data. At the moment, organizations like BGI appear to be generating revenue by sequencing everything under the sun, but cheaper and cheaper boxes might mean that the BGI operations outside of clinical sequencing aren't cost effective going forward. Once the razors (electric, disposable, whatever) get cheap enough, you no longer bother going to the barber for a shave.

I will continue to work with the data in an effort to make the plots simpler and therefore hopefully more compelling.

Planning for Toy Story and Synthetic Biology: It's All About Competition (Updated)

2013-04-18T04:00:00Z

Here are updated cost and productivity curves for DNA sequencing and synthesis. Reading and writing DNA is becoming ever cheaper and easier. The Economist and others call these "Carlson Curves", a name I am ambivalent about but have come to accept if only for the good advertising. I've been meaning to post updates for a few weeks; the appearance today of an opinion piece at Wired about Moore's Law serves as a catalyst to launch them into the world. In particular, two points need some attention, the notions that Moore's Law 1) is unplanned and unpredictable, and 2) somehow represents the maximum pace of technological innovation.

DNA Sequencing Productivity is Skyrocketing

First up: the productivity curve. Readers new to these metrics might want to have a look at my first paper on the subject, "The Pace and Proliferation of Biological Technologies" (PDF) from 2003, which describes why I chose to compare the productivity enabled by commercially available sequencing and synthesis instruments to Moore's Law. (Briefly, Moore's Law is a proxy for productivity; more transistors putatively means more stuff gets done.) You have to choose some sort of metric when making comparisons across such widely different technologies, and, however much I hunt around for something better, productivity always emerges at the top.

It's been a few years since I updated this chart. The primary reason for the delay is that, with the profusion of different sequencing platforms, it became somewhat difficult to compare productivity [bases/person/day] across platforms. Fortunately, a number of papers have come out recently that either directly make that calculation or provide enough information for me to make an estimate. (I will publish a full bibliography in a paper later this year. For now, this blog post serves as the primary citation for the figure below.)

Visual inspection reveals a number of interesting things. First, the DNA synthesis productivity line stops in about 2008 because there have been no new instruments released publicly since then. New synthesis and assembly technologies are under development by at least two firms, which have announced they will run centralized foundries and not sell instruments. More on this later.

Second, it is clear that DNA sequencing platforms are improving very rapidly, now much faster than Moore's Law. This is interesting in itself, but I point it out here because of the post today at Wired by Pixar co-founder Alvy Ray Smith, "How Pixar Used Moore's Law to Predict the Future". Smith suggests that "Moore's Law reflects the top rate at which humans can innovate. If we could proceed faster, we would," and that "Hardly anyone can see across even the next crank of the Moore's Law clock."

Moore's Law is a Business Model and is All About Planning -- Theirs and Yours

As I have written previously, early on at Intel it was recognized that Moore's Law is a business model (see the Pace and Proliferation paper, my book, and in a previous post, "The Origin of Moore's Law"). Moore's Law was always about economics and planning in a multi-billion dollar industry. When I started writing about all this in 2000, a new chip fab cost about $1 billion. Now, according to The Economist, Intel estimates a new chip fab costs about $10 billion. (There is probably another Law to be named here, something about exponential increases in cost of semiconductor processing as an inverse function of feature size. Update: This turns out to be Rock's Law.) Nobody spends $10 billion without a great deal of planning, and in particular nobody borrows that much from banks or other financial institutions without demonstrating a long-term plan to pay off the loan. Moreover, Intel has had to coordinate the manufacturing and delivery of very expensive, very complex semiconductor processing instruments made by other companies. Thus Intel's planning cycle explicitly extends many years into the future; the company sees not just the next crank of the Moore's Law clock, but several cranks. New technology has certainly been required to achieve these planning goals, but that is just part of the research, development, and design process for Intel. What is clear from comments by Carver Mead and others is that even if the path was unclear at times, the industry was confident that they could to get to the next crank of the clock.

Moore's Law served a second purpose for Intel, and one that is less well recognized but arguably more important; Moore's Law was a pace selected to enable Intel to win. That is why Andy Grove ran around Intel pushing for financial scale (see "The Origin of Moore's Law"). I have more historical work to do here, but it is pretty clear that Intel successfully organized an entire industry to move at a pace only it could survive. And only Intel did survive. Yes, there are competitors in specialty chips and in memory or GPUs, but as far as high volume, general CPUs go, Intel is the last man standing. Finally, and alas I don't have a source anywhere for this other than hearsay, Intel could have in fact gone faster than Moore's Law. Here is the hearsay: Gordon Moore told Danny Hillis who told me that Intel could have gone faster. (If anybody has a better source for that particular point, give me a yell on Twitter.) The inescapable conclusion from all this is that the management of Intel made a very careful calculation. They evaluated product roll-outs to consumers, the rate of new product adoption, the rate of semiconductor processing improvements, and the financial requirements for building the next chip fab line, and then set a pace that nobody else could match but that left Intel plenty of headroom for future products. It was all about planning.

The reason I bother to point all this out is that Pixar was able to use Moore's Law to "predict the future" precisely because Intel meticulously planned that future. (Calling Alan Kay: "The best way to predict the future is to invent it.") Which brings us back to biology. Whereas Moore's Law is all about Intel and photolithography, the reason that productivity in DNA sequencing is going through the roof is competition among not just companies but among technologies. And we only just getting started. As Smith writes in his Wired piece, Moore's Law tells you that "Everything good about computers gets an order of magnitude better every five years." Which is great: it enabled other industries and companies to plan in the same way Pixar did. But Moore's Law doesn't tell you anything about any other technology, because Moore's Law was about building a monopoly atop an extremely narrow technology base. In contrast, there are many different DNA sequencing technologies emerging because many different entrepreneurs and companies are inventing the future.

The first consequence of all this competition and invention is that it makes my job of predicting the future very difficult. This emphasizes the difference between Moore's Law and Carlson Curves (it still feels so weird to write my own name like that): whereas Intel and the semiconductor industry were meeting planning goals, I am simply keeping track of data. There is no real industry-wide planning in DNA synthesis or sequencing, other than a race to get to the "$1000 genome" before the next guy. (Yes, there is a vague road-mappy thing promoted by the NIH that accompanied some of its grant programs, but there is little if any coordination because there is intense competition.)

Biological Technologies are Hard to Predict in Part Because They Are Cheaper than Chips

Compared to other industries, the barrier to entry in biological technologies is pretty low. Unlike chip fabs, there is nothing in biology that costs $10 billion commercially, nor even $1 billion. (I have come to mostly disbelieve pharma industry claims that developing drugs is actually that expensive, but that is another story for another time.) The Boeing 787 reportedly cost $32 billion to develop as of 2011, and that is on top of a century of multi-billion dollar aviation projects that had to come before the 787.

There are two kinds of costs that are important to distinguish here. The first is the cost of developing and commercializing a particular product. Based on the money reportedly raised and spent by Life, Illumina, Ion Torrent (before acquisition), Pacific Biosciences, Complete Genomics (before acquisition), and others, it looks like developing and marketing second-generation sequencing technology can cost upwards of about $100 million. Even more money gets spent, and lost, in operations before anybody is in the black. My intuition says that the development costs are probably falling as sequencing starts to rely more on other technology bases, for example semiconductor processing and sensor technology, but I don't know of any real data. I would also guess that nanopore sequencing, should it actually become a commercial product this year, will have cost less to develop than other technologies, but, again, that is my intuition based on my time in clean rooms and at the wet bench. I don't think there is great information yet here, so I will suspend discussion for the time being.

The second kind of cost to keep in mind is the use of new technologies to get something done. Which brings in the cost curve. Again, the forthcoming paper will contain appropriate references.

The cost per base of DNA sequencing has clearly plummeted lately. I don't think there is much to be made of the apparent slow-down in the last couple of years. The NIH version of this plot has more fine grained data, and it also directly compares the cost of sequencing with the cost per megabyte for memory, another form of Moore's Law. Both my productivity plot above and the NIH plot show that sequencing has at times improved much faster than Moore's Law, and generally no slower.

If you ponder the various wiggles, it may be true that the fall in sequencing cost is returning to a slower pace after a period in which new technologies dramatically changed the market. Time will tell. (The wiggles certainly make prediction difficult.) One feature of the rapid fall in sequencing costs is that it makes the slow-down in synthesis look smaller; see this earlier post for different scale plots and a discussion of the evaporating maximum profit margin for long, double-stranded synthetic DNA (the difference between the orange and yellow lines above).

Whereas competition among companies and technologies is driving down sequencing costs, the lack of competition among synthesis companies has contributed to a stagnation in price decreases. I've covered this in previous posts (and in this Nature Biotech article), but it boils down to the fact that synthetic DNA has become a commodity produced using relatively old technology.

Where Are We Headed?

Now, after concluding that the structure of the industry makes it hard to prognosticate, I must of course prognosticate. In DNA sequencing, all hell is breaking loose, and that is great for the user. Whether instrument developers thrive is another matter entirely. As usual with start-ups and disruptive technologies, surviving first contact with the market is all about execution. I'll have an additional post soon on how DNA sequencing performance has changed over the years, and what the launch of nanopore sequencing might mean.

DNA synthesis may also see some change soon. The industry as it exists today is based on chemistry that is several decades old. The common implementation of that chemistry has heretofore set a floor on the cost of short and long synthetic DNA, and in particular the cost of synthetic genes. However, at least two companies are claiming to have technology that facilitates busting through that cost floor by enabling the use of smaller amounts of poorer quality, and thus less expensive, synthetic DNA to build synthetic genes and chromosomes.

Gen9 is already on the market with synthetic genes selling for something like $.07 per base. I am not aware of published cost estimates for production, other than the CEO claiming it will soon drop by orders of magnitude. Cambrian Genomics has a related technology and its CEO suggests costs will immediately fall by 5 orders of magnitude. Of course, neither company is likely to drop prices so far at the beginning, but rather will set prices to undercut existing companies and grab market share. Assuming Gen9 and Cambrian don't collude on pricing, and assuming the technologies work as they expect, the existence of competition should lead to substantially lower prices on genes and chromosomes within the year. We will have to see how things actually work in the market. Finally, Synthetic Genomics has announced it will collaborate with IDT to sell synthetic genes, but as far as I am aware nothing new is actually shipping yet, nor have they announced pricing.

So, supposedly we are soon going to have lots more, lots cheaper DNA. But you have to ask yourself who is going to use all this DNA, and for what. The important business point here is that both Gen9 and Cambrian Genomics are working on the hypothesis that demand will increase markedly (by orders of magnitude) as the price falls. Yet nobody can design a synthetic genetic circuit with more than a handful of components at the moment, which is something of a bottleneck on demand. Another option is that customers will do less up-front predictive design and instead do more screening of variants. This is how Amyris works -- despite their other difficulties, Amyris does have a truly impressive metabolic screening operation -- and there are several start-ups planning to provide similar (or even improved) high-throughput screening services for libraries of metabolic pathways. I infer this is the strategy at Synthetic Genomics as well. This all may work out well for both customers and DNA synthesis providers. Again, I think people are working on an implicit hypothesis of radically increased demand, and it would be better to make the hypothesis explicit in part to identify the risk of getting it wrong. As Naveen Jain says, successful entrepreneurs are good at eliminating risk, and I worry a bit that the new DNA synthesis companies are not paying enough attention on this point.

There are relatively simple scaling calculations that will determine the health of the industry. Intel knew that it could grow financially in the context of exponentially falling transistor costs by shipping exponentially more transistors every quarter -- that is the business model of Moore's Law. Customers and developers could plan product capabilities, just as Pixar did, knowing that Moore's Law was likely to hold for years to come. But that was in the context of an effective pricing monopoly. The question for synthetic gene companies is whether the market will grow fast enough to provide adequate revenues when prices fall due to competition. To keep revenues up, they will then have to ship lots of bases, probably orders of magnitudes more bases. If prices don't fall, then something screwy is happening. If prices do fall, they are likely to fall quickly as companies battle for market share. It seems like another inevitable race to the bottom. Probably good for the consumer; probably bad for the producer.

(Updated) Ultimately, for a new wave of DNA synthesis companies to be successful, they have to provide the customer something of value. I suspect there will be plenty of academic customers for cheaper genes. However, I am not so sure about commercial uptake. Here's why: DNA is always going to be a small cost of developing a product, and it isn't obvious making that small cost even cheaper helps your average corporate lab.

In general, the R part of R&D only accounts for 1-10% of the cost of the final product. The vast majority of development costs are in polishing up the product into something customers will actually buy. If those costs are in the neighborhood of $50-100 million, the reducing the cost of synthetic DNA from $50,000 to $500 is nice, but the corporate scientist-customer is more worried about knocking a factor of two, or an order of magnitude, off the $50 million. This means that in order to make a big impact (and presumably to increase demand adequately) radically cheaper DNA must be coupled to innovations that reduce the rest of the product development costs. As suggested above, forward design of complex circuits is not going to be adequate innovation any time soon. The way out here may be high-throughput screening operations that enable testing many variant pathways simultaneously. But note that this is not just another hypothesis about how the immediate future of engineering biology will change, but another unacknowledged hypothesis. It might turn out to be wrong.

The upshot, just as I wrote in 2003, is that the market dynamics of biological technologies will remain difficult to predict precisely because of the diversity of technology and the difficulty of the tasks at hand. We can plan on prices going down; how much, I wouldn't want to predict.

Updated US Craft Brewing Chart

2013-03-02T18:55:32Z

Here is an updated version of the chart from "Microbrewing the Bioeconomy: Beer as an Example of Distributed Manufacturing" (PDF). Note that the x-axis is decadal on the main chart and that 2011 and 2012 are tacked on to the outside. There is still very strong growth in the number of craft breweries in the US.

Meeting on Conservation and Synthetic Biology, April 9-11

2013-02-28T20:31:47Z

How will synthetic biology and conservation shape the future of nature?

April 9-11, 2013

Clare College

Cambridge, England

Sponsored by the Wildlife Conservation Society. More info, including the agenda, here.

Scheduled speakers include: Dick Kitney, Georgina Mace, Kent Redford, Karen Esler, Rob Carlson, Sofia Alendra Valenzuela Aguila, Jay Keasling, Mildred Cho, Oliver Morton, Bertina Ceccarelli, Stewart Brand, and many others.

Are These The Drones We're Looking For? (Part IV)

2012-10-12T06:30:27Z

(Pt 1, Drones for Destruction, Construction, and Distribution; Pt II, Pirate Hunting in the Clouds; Pt III, Photos, Bullets, and Smuggling)

The Coming War Overhead

Are you ready for drone dogfights? How about combat flocks and swarms? They are coming. And they will be over your head before you know it.

From my office window I am fortunate to often see eagles and hawks in flight over Seattle's Lake Union. These raptors are regularly harassed by smaller birds attempting to run off potential predators or competitors. Each species - whether predator and prey - clearly employs different tactics based on size, speed, armaments, number of combatants, etc. Within a few years this aerial combat will become a frequent sight in the U.S., but rather than raptors, crows, and gulls, the combatants will be drones of all shapes and sizes. I am not at all sure that we are adequately prepared, or whether we are adequately planning, for the strange world ahead.

This battle will be engaged on many different fronts. Left, right, black hat, white hat, criminal, law enforcement: all will have the same tools at their disposal. Even if federal, state, and local agencies have early access to hand-me down technologies developed for military applications, they will be up against a large number of innovators, many of whom come from open-source, hacker communities where innovation runs faster than anywhere else.

I have outlined the playing field (Quidditch pitch?) in prior installments. The capability to produce and hack drones is already widely distributed. Drones can now cooperate in swarms to build structures, play music, and play catch. Economic incentives - as well as the cool factor - strongly favor the development of ever less expensive and ever more capable drones to be used for photography, shipping, data storage, and communications, just to name a few applications. As drones and the services they provide become more valuable, and as they inevitably become useful for supplying illicit products such as drugs and pirated music and movies, attempts at regulating drone use are likely to increase demand. This is the very definition of 'perverse incentives'. Yet with the capability to produce drones already so democratized, the only way to limit their use is likely to be direct force. And thus the combat capabilities of even simple drones will, like printing, file-sharing, and every market for every illicit drug, become an arena of continual technological oneupmanship. Drone enthusiasts who work on national security issues have already started a "Drone Smackdown" tourney to explore tactics in their spare time.

So it isn't at all hard to imagine that somewhere down this road we will see a mashup of cheap drones and the sort of Shanzai warfare recently seen in Libya, and now in Syria, in which irregular forces hack together their own knock-off versions of much more expensive (and much more capable) weapons systems they have probably only seen on the Internet. But those DIY weapons systems seem to have done the job. So, too, will Shanzai combat drones.

Here is what we can look forward to: projectiles, nets, lasers or LEDs to blind cameras, strings dropped or shot onto rotors, aerosol cans turned into flying flamethrowers, salt water spray, chaff to disrupt near-field or optical communications, and simple electronic jamming. And each offensive mode will breed countermeasures. The fruits of idle and motivated minds will germinate. Almost any cheap drone will probably have a spare servo circuit or two to control on-board munitions. Adding capacity will be trivial. Remember: many drones are already flying smart phones, so whatever the mission, there's an app for that (see Pt I).

There will be casualties in these confrontations. The drones, certainly, will suffer. But sometimes the countermeasures will miss, causing damage to whatever and whomever is downrange. And when drones are successfully destroyed, they will fall down. Onto things. And onto people. Such as when a Sheriff's Department in Texas dropped a big drone onto it's own SWAT team. Fortunately, the team was sheltered inside their armored car; we should all be so lucky.

In short, the drivers for an arms race are multifold: potential invasion of privacy by government or commercial drones (see Pt. III), attack and defense of file sharing swarms, attacks on (or hijacking of) and defense of cargo drones. As costs fall, and capabilities improve, novel applications will emerge that will in turn drive ever more innovation in drone weapons systems, especially in countermeasures.

Regardless of what the rules are, of what the FAA and other authorities decide to allow, the economic incentives to employ drones as I have described above will drive behavior. There are just no two ways about it. We will be seeing some version of the world I have described in this series of posts. Consequently, any regulatory should facilitate the safe use of drones rather than attempt to constrain their use. What troubles me, and what motivated me to explore this topic, is that ongoing discussions of drone regulations will completely miss both the economic drivers and the technological ferment making it all possible. I'd like to be wrong about that, but history is likely to be an excellent guide. In the case of drones, as in every other attempt to regulate a democratized technology that serves a large and growing market, black markets will emerge. Nefarious applications of drones are inevitable, and poorly conceived regulation will be an accelerant that makes the problem worse. This is not an argument that all regulation is bad, merely an argument that regulation will be as poorly considered and poorly applied to drones as it was in all the other technological cases I have studied.

Finally, we must remember, first and foremost, that humans will continue to be the targets of armed drones wherever they fly. And, like the raptors that inspired me to think about drone combat, U.S. innovations in arming drones will come home to roost. That is the world we should be preparing for; have no illusions otherwise.

Are These The Drones We're Looking For? (Part III)

2012-10-01T19:14:06Z

(Pt I, Drones for Destruction, Construction, and Distribution; Pt II, Pirate Hunting in the Clouds)

Photos, Bullets, and Smuggling

Unmanned aerial photography drones look to be the next big thing. They also look to be highly annoying and invasive. Earlier this year, the New York Times described a Los Angeles drone operator who had already been approached by paparazzi to take photos of celebrities. Until regulatory issues got in the way, his previous job was in aerial real-estate photography, where there is also big demand. The Times article describes how the FAA must decide on rules for commercial drone use in aerial photography, among many other applications, by 2015. But it is the paparazzi gig that should get you thinking.

The reason the paparazzi take photos of famous people is money. Famous people have money, and notoriety, and other people for some reason pay to peek in their windows and, frankly, up their skirts. What is going to happen when paparazzi start to use drones? Let's call these robots dronarazzi. (According to Wikipedia, the word paparazzi comes from Fellini's La Dolce Vita and is meant to suggest an annoying, buzzing, insect. My neologism may be superfluous given the racket current drones make, but it seems important to distinguish between humans and drones, don't you think?) Very quickly after dronarazzi appear, famous people will attempt to use their money to get laws passed against them. Those laws will turn out to be unenforceable due to the profusion of hardware so cheap that it is disposable. Famous, wealthy people will then spend some of their money to physically remove the annoyance of the dronarazzi. And there it begins: drone countermeasures.

Drones have already been the subject of armed confrontation within U.S. borders. Recently, hunters in Texas unhappy about a surveillance drone flown by animal rights activists proceeded to pretend it was a game bird. The shoot-down was likely illegal; undoubtedly lawsuits are afoot. As more drones take to the sky, there will certainly be more such confrontations. Surveillance drones flown by law enforcement agencies, the DEA, and U.S. Customs will certainly be targets. Even before law enforcement agencies find themselves involved in daily skirmishes we will see countermeasures innovations crop up in -- no surprise here -- California. Hollywood, to be specific. I would expect the first dronarazzi shoot-downs to happen fairly soon, even before the FAA sorts out the relevant regulations. And given how frequently paparazzi crash their cars into each other, their subjects, and bystanders, we can expect dronarazzi to cause analogous physical damage.

But look ahead just a bit, beyond photography, to a time when drones are providing real-time traffic or crowd monitoring, perhaps combined with face recognition, which you, the surveilled, may not want to allow. What will the market look like for gizmos that prevent airborne cameras from imaging your face? Or what about when small, VTOL drones are actually moving stuff around in the real world. That stuff could conceivably be your latest, packet-switched delivery from Amazon, or it could be the latest methamphetamine delivery from your drug dealer; it will be hard to tell the difference without physical inspection. Law enforcement will want to track -- and almost certainly to inspect -- those cargoes, and many a sender and recipient will want to thwart both tracking and inspection.

The rules for drone flight set by the FAA will probably attempt to spell out specific allowed uses. This decision will be informed both by 9/11 and by recent U.S. combat experience. We might see the definition of specific drone flight corridors, or specific drone flight characteristics, and federal, state, and local authorities may demand the ability to override the controls on drones through back doors in software. But those back doors will be vulnerable to misuse, and are likely to be nailed shut even by above-board drone operators. Who wants to loose control of a drone to the hacker kid next door? And, obviously, the economic incentive to cheat in the face of any drone flight or construction regulations will be absolutely enormous. Many people will make the calculation (probably correctly) that, in the unlikely event that a suspect drone itself is caught or disabled, the operator will walk away scot-free because it simply may not be possible to identify her. Yet I suspect that whatever the rules forwarded by the FAA, and whatever powers of intervention in drone activity are given to law enforcement, that it will all come down to whether people can be physically prevented from doing what they want with drones. That is, can drone flight rules actually be enforced without the hands-on ability to capture or shut down scofflaw drones and operators? The answer, very likely, is no, especially given the existing community of drone hackers who are proficient at producing both hardware and software. This brings us back to the proliferation of physical and electronic countermeasures. And I question whether we are adequately planning for the future.

(Coming soon, Part IV: The Coming War Overhead)

Are These The Drones We're Looking For? (Part II)

2012-09-28T15:15:00Z

(Pt 1, Drones for Destruction, Construction, and Distribution)

Pirate Hunting in the Clouds

Piracy is a perennial weed. For example, coordinated efforts to shut down electronic file sharing have had little effect; you can still find anything you want online. The reason, of course, is that pirate hunters are always playing catchup to technological innovation that facilitates the anonymous movement of bits. That should be no surprise to anyone involved, because the same sort of technological struggle has been present in print piracy since the days of Johannes Gutenberg. Music, game, and movie piracy is just the same game on a new field.

The latest innovation in file sharing looks to be drones. Two groups, The Pirate Bay (TPB) and Electronic Countermeasures, are building swarms of file-sharing drones meant to decentralize information storage and communications. TPB, in particular, propounds an ideology of sharing everything they can get their hands on by any means available. Says one contributor, "Everyone knows WHAT TPB is. Now they're going to have to think about WHERE TPB is." File sharing may soon be located both metaphorically and physically in the clouds.

How will pirate-hunters respond to airborne, file-sharing drones? Attempts will certainly be made to regulate airborne networks. But that approach will probably fail, because regulation rarely makes headway against ideology. Along with regulation will come electronic efforts to disrupt drone networks by jamming broadcasts and disrupting intraswarm communications. That is likely to fail as well, because the drone networks will employ frequency bands used for many other devices, which will make drone-specific jamming technologically implausible, especially in signal-rich, urban environments. Finally, both government and industry will embark on physically attacking the drones (to which I return to in a moment). But that isn't going to work either, because drones will soon be cheap enough to fire and forget.

At the moment, the hardware for each of the file-sharing drones is a bit pricy, north of $1000. Inevitably, the cost will come down. Quite capable toy quadcopters are available for only a few hundred dollars, whereas just a few years ago the same bird cost thousands. You can be sure that other form factors will be used, too. Fixed-wing and lighter-than-air drones are experiencing the same pressure for innovation as four-, six-, and eight-bladed 'copters. Regardless of what sort of drones are employed in the network, any concerted effort to physically disrupt drones will simply result in more innovation and cost reduction by those who want to keep them in the air. The economic motivation to fly drones in the face of regulations is compelling, whether for smuggling atoms or bits, and as a result there is every reason to think there will be clouds of drones in the air relatively soon.

As we start down this road, what's missing from the conversation is a concerted effort to ask, "What's next?" Authorities might imagine they can constrain access to the physical hardware, but the manufacturing of drones is already well beyond anyone's control. Any attempt at restricting access or use will merely create perverse incentives for greater innovation.

Hackers regularly modify commercially available drones to their own ends. Beyond what comes in a kit, structural components for drones can be 3D-printed, with open source CAD files and parts lists available at Thingverse and other repositories. Whatever mechanical parts (such as propellers) that are not now easily printable will undoubtedly soon be, and in any case can be easily molded in a variety of plastics. MIT just announced a project to develop printable robots. While the MIT paper 'bots are described as being terrestrial, you have to imagine that boffins are already cooking up aerial versions. Contributing to the air of innovation, DARPA even runs a crowd-sourced UAV design competition, UAVForge.

So much for the hardware; what about control software? The University of Pennsylvania's Vijay Kumar and his collaborators at the GRASP Lab literally have drones jumping through hoops on command, and cooperating both to fly in formation and to build large structures. This academic project will certainly result in the publication of papers describing the relevant control algorithms, and quite probably the publication of the control code itself. Imagining GRASP Lab projects out in the wild gives you something to think about. When you put all this together, the combination of distributed designs and distributed manufacturing employing readily available motors and drive electronics mean that, in the words of open source advocate Bruce Perens, "innovation has gone public". (For more on that meme, see Perens' The Emerging Economic Paradigm of Open Source.) As a result, there is no physical means available to law enforcement, or to anyone else, to either control access to drones or to control their use. Combining wide access to hardware with inevitably open-source control code will produce a profusion of drone swarms. And yet some authorities will inevitably try to restrict access and use of drones, both in the name of public safety and to maintain a technological edge over putative scofflaws. Up next: what if attempts at regulation just make things worse?

(Part III Photos, Shooting Bullets, and Smuggling)

Are These The Drones We're Looking For? (Part I)

2012-09-27T04:00:00Z

Drones for Destruction, Construction, and Distribution

Drones, it seems, are everywhere. The news is full of the rapidly expanding use of drones in combat. The U.S. government uses drones daily to gather intelligence and to kill people. Other organizations, ranging from organized militaries in China, Israel, and Iran to militias like Hezbollah, aspire to possess similar capabilities. Amateurs are in the thick of it, too; if a recent online video is to be believed, a few months of effort is all that is necessary to develop a DIY drone capable of deploying DIY antipersonnel ordinance.

Lest we think drones are only used to create mayhem, they are used to create beauty. Last year's lovely art project Flight Assembled Architecture employed a centrally-controlled swarm of small drones to build a complex, curving tower 6 meters tall. Operating in a highly controlled environment, fully outfitted with navigational aides, each drone had to position itself precisely in six degrees of freedom (three in space, and three in rotation) in order to place each building block. As our urban areas become sensor-rich environments, drones will soon have these remarkable navigational capabilities just about anywhere people live at high densities, namely urban environments.

To understand the future capabilities of drones, you need merely think of them as flying smartphones running apps. That's not a great leap, because smartphones are already used as the brains for some drones. The availability of standard iPhones and Android phones has enabled a thriving market of third-party apps that provide ever new capabilities to the user. Drone platforms will benefit from analogous app development. Moreover, as hardware improves, so will the capabilities of apps. For example, Broadcom recently announced a new chip that enables the integration of multiple kinds of signals -- GPS, magnetometer, altimeter, wi-fi, cell phone tower, gyroscopes, etc. -- and that "promises to indicate location ultra-precisely, possibly within a few centimeters, vertically and horizontally, indoors and out." The advertised application of that chip is for cell phones, but you can be sure the chips will find their way into drones, if only via cell phones, and will then quickly be utilized by guidance apps. Whatever the drone mission may be, there will be an app for that.

When those individual, sensor-laden drones can cooperate, things get even more interesting. Vijay Kumar's recent TED talk has must-see video of coordinated swarms of quad-rotor drones. The drones, built at the GRASP Lab at the University of Pennsylvania, fly in formation, map outdoor and indoor environments, and as an ensemble play music on oversized instruments (see Double-O-Drone). As you watch the videos, pay close attention to how well the drones understand their own position and speed, and how that information improves their flight capabilities. When equipped with GPS and other sorts of sensors, drones are clearly capable of not just finding their way around complex environments but also of manipulating those environments. At the moment, the drones' brains are actually in a stationary computer, with both sensory data and flight instructions wirelessly broadcast to and fro. Moore's Law guarantees that those brains - including derivatives of the aforementioned Broadcom chip - will soon reside on the drones, thereby enabling real-time, local control, which will be necessary for autonomous operations at any real distance from home base. The drones will become birds. But these birds will have vertical take-off and landing (VTOL) capabilities, substantial load-carrying capacity, and will be able to work together towards ends set by humans.

A company called Matternet is already planning to exploit these capabilities. The company's initial business model involves transporting goods in developing countries that lack adequate infrastructure. If this strategy is successful, and if it can be scaled up, it will negate the need to build much of the fixed infrastructure that exists in the developed world. It is a 21st century version of the Pony Express: think packet-switching, which makes the internet work efficiently, but for atoms rather than for bits.

Matternet plans that the first goods moved this way will be small, high value, perishables like pharmaceuticals. But cargo size needn't be limited. As Vijay Kumar pointed out in his TED talk, drones can cooperate to lift and transport larger objects. While undoubtedly power or fuel will constrain some of these plans until technology catches up to aspirations, drones will inevitably be used to move larger and larger objects over longer and longer distances. The technology will also be used very soon in the U.S. The FAA has been directed to come up with rules for commercial drone use by 2015, and must sort out how to enable emergency agencies to use drones in 2012. There are already 61 organizations in the U.S. with permission to fly drones in civilian airspace. Yet rather less thought has been given to drone use outside the rules. We are planning for drones, after a fashion, but what about after they arrive?

(Part II: Pirate Hunting in the Clouds)

Biodefense Net Assessment: Causes and Consequences of Bioeconomic Proliferation

2012-09-05T13:22:25Z

Revenues from biotechnology continue to grow rapidly around the world. For several years I have been trying to assess these revenues, in part as a proxy metric for technological capabilities. A couple of years ago, I received a commission from the U.S. government to explore this topic for the 2012 Biodefense Net Assessment (BNA). I recently received approval to release the resulting report, which carries the title "Causes and Consequences of Bioeconomic Proliferation: Implications for U.S. Physical and Economic Security" (PDF). As far as I am aware, this is the first publicly-released document from the BNA.

There is a relatively small amount of information available about the BNA available on the web. The BNA is a quadrennial review required under Homeland Security Presidential Directive 10 (HSPD-10): "These assessments are meant to provide senior level decision makers with fresh, non-consensus, perspectives on key issues underlying the Nation's biodefense." The first few pages of the report provide more information about the origin and use of the BNA.

My own motivation for doing this work is to better understand what is going on in the world. When it comes to developing policy to improve security and safety, I unapologetically insist that data drive policy. There are far too many people who develop policy in spite of data rather than in light of data. That leads to messy thinking and demonstrably makes us less safe and less secure. All that said, one conclusion from my work on this report is that nobody is doing a very good job of gathering and publishing the data necessary to understand the rapid technical and economic development of biotechnology around the world.

One final thought about the report: this particular document was funded by the U.S. government, and I was given a particular set of charges in the task (see pg iii-iv); the report is therefore tilted toward U.S. security concerns. However, the basic analyses and conclusions are relevant to developing policy in any country, and for that matter to developing strategy for many private companies and other organizations. I will continue work on this story, and look forward to engaging people around the globe in better understanding how our world is changing.

Here is the "Background" section of the report. Please note that the report is now a few years old, and the bioeconomy has continued to grow rapidly around the world.

Biotechnology is becoming increasingly de-skilled and less expensive, leading to a proliferation of localized innovation around the world. In addition to major investments by growing economic powerhouses India and China, other developing countries such as Indonesia, Pakistan, and Brazil are equally intent on developing domestic biotech research and development capabilities. All of these countries are interested initially in producing drugs for diseases that predominantly affect their citizens, a project that requires a particular infrastructure and set of skills. Yet those same skills can be used to develop other applications, from fuels and materials to weapons, all of which can serve as a lever to increase power and presence on the world stage, thereby enabling developing countries to become rivals to the US both regionally and globally.

Economic demand will serve as a driver for ever greater proliferation of biotechnology. Today, in the US, revenues from genetically modified systems contribute the equivalent of almost 2% of GDP, and are growing in the range of 15 to 20% per year. China, among other countries, is not far behind and is following explicit government policy to substantially increase its independent, domestic development of new biological technologies to address such diverse concerns as healthcare, biomass production, and biomanufacturing. As is already the case in many other industries, trade between developing nations in biotech may soon exceed trade with the US. Therefore, among the challenges the US is likely to face in this environment is that the flow of technology, ideas, and skills may bypass US soil. Moreover, because skills and instrumentation are widely available, biotechnological development is possible in unconventional settings outside of universities and corporate laboratories. The resulting profusion of localized and distributed innovation is likely to provide a wide variety of challenges to US security, from economic competition, to intelligence gathering, to the production of new bio-threats.

Urban Escape Interview at PICNIC '11

2012-05-01T20:02:23Z

Last fall at PICNIC '11, I did an Urban Escape "Floating Interview" with Mitchel Joachim (NYU, Terraform ONE) and Oliver Medvedik (Genspace). We talked about innovation, ecology, architecture, the bioeconomy, and re-imagining cities. Here is a brief description, with some quotes.

And here is a video summary of the first day, with me enthusing about PICNIC, one of my favorite communities.

Upcoming Talks in New York Area

2012-05-01T18:48:45Z

I'm headed to the New York area this week and will be giving three talks (two of which are open to the public).

May 4th, Noon, Princeton University: "Biology is Technology: Garage Biology, Microbrewing and the Economic Drivers of Distributed Biological Production"

May 5th, 1 pm, Genspace (33 Flatbush Avenue, Brooklyn): "Biology Is Technology: The Implications of Global Biotechnology"

May 7th-8th, The Hastings Institute, "Progress and Prospects for Microbial Biofuels" for the next round of conversations on ethics, synthetic biology, and public policy. The previous round of conversations is captured in this set of essays, which includes my contribution, "Staying Sober About Science" (free after registration).

Synthetic biology and "green" explosives

2012-05-01T18:38:40Z

Here is my article with Dan Grushkin for Slate and Future Tense on "The Military's Push to Green Our Explosives", about using synthetic biology to make things go boom. We had way more material than space, and we should probably write something else on the topic.

Here are the first three 'graphs:

Last year, when the United States military debuted footage of an iridescent drone the size and shape of a hummingbird buzzing around a parking lot, the media throated a collective hooah! Time magazine even devoted a cover to it. Meanwhile, with no fanfare at all--despite the enormous potential to reshape modern warfare--the military issued a request for scientists to find ways to design microbes that could produce explosives for weapons. Imagine a vat of genetically engineered yeast that produces chemicals for bombs and missiles instead of beer.

The request takes advantage of new research in synthetic biology, a science that applies engineering principles to genetics. To its humanitarian credit, in the field's short existence, scientists have genetically programmed bacteria and yeast to cheaply produce green jet fuels (now being tested by major airplane makers) and malaria medicines (scheduled for market in 2013). It's an auspicious beginning for a science that portends to revolutionize how we make things. In the future, we may harness cells to self-assemble into far more complex objects like cell phone batteries or behave like tiny programmable computers. The promise, however, comes yoked with risks.

The techniques that make synthetic biology such a powerful tool for positive innovation may be also used for destruction. The military's new search for biologically brewed explosives threatens to reopen an avenue of research that has been closed for 37 years: biotechnology developed for use in war.

The Deadliest Virus

2012-05-01T18:35:05Z

Here is Michael Specter's New Yorker piece on H5N1 influenza, "The Dealiest Virus", which has extensive comments by me (the article is paywalled, unfortunately).

Deliberating Over the Danger from H5N1

2012-05-01T18:25:50Z

Here is an article from The Scientist in which I and others debate the wisdom of pursuing and publishing research into influenza viruses: "Deliberating Over Danger".

For background, see my earlier post "Censoring Science is Detrimental to Security".