I want to focus on a third conception of synthetic biology: the idea of turning biotechnology from an artisa.n.a.l process of one- off creations, developed with customized techniques, to a true engineering discipline, using processes and parts that are as standardized and as well understood as valves, screws, capacitors, or resistors. The electrical engineer told to build a circuit does not go out and invent her own switches or capacitors. She can build a circuit using off-the-shelf components whose performance is expressed using standard measurements. This is the dream of one group of synthetic biologists: that biological engineering truly become engineering, with biological black boxes that perform all of the standard functions of electrical or mechanical engineering--measuring flow, reacting to a high signal by giving out a low signal, or vice versa, starting or terminating a sequence, connecting the energy of one process to another, and so on.

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Of course an engineer understands the principle behind a ratchet, or a valve, but he does not have to go through the process of thinking "as part of this design, I will have to create a thing that lets stuff flow through one way and not the other." The valve is the mechanical unit that stands for that thought, a concept reified in standardized material form which does not need to be taken apart and pa.r.s.ed each time it is used.

By contrast, the synthetic biologists claim, much of current biotechnological experimentation operates the way a seventeenth- century artisan did. Think of the gunsmith making beautiful one- off cla.s.sics for his aristocratic patrons, without standardized calibers, parts, or even standard-gauge springs or screws. The process produces the gun, but it does not use, or produce, standard parts that can also be used by the next gunsmith.

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Is this portrayal of biology correct? Does it involve some hyping of the new hot field, some denigration of the older techniques? I would be shocked, shocked, to find there was hype involved in the scientific or academic enterprise. But whatever the degree to which the novelty of this process is being subtly inflated, it is hard to avoid being impressed by the projects that this group of synthetic biologists has undertaken. The MIT Registry of Standard Biological Parts, for example, has exactly the goal I have just described.

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The development of well-specified, standard, and interchangeable biological parts is a critical step towards the design and construction of integrated biological systems. The MIT Registry of Standard Biological Parts supports this goal by recording and indexing biological parts that are currently being built and offering synthesis and a.s.sembly services to construct new parts, devices, and systems. . . . In the summer of 2004, the Registry contained about 100 basic parts such as operators, protein coding regions, and transcriptional terminators, and devices such as logic gates built from these basic parts. Today the number of parts has increased to about 700 available parts and 2000 defined parts. The Registry believes in the idea that a standard biological part should be well specified and able to be paired with other parts into suba.s.semblies and whole systems.

Once the parameters of these parts are determined and standardized, simulation and design of genetic systems will become easier and more reliable. The parts in the Registry are not simply segments of DNA, they are functional units.9 43

Using the Registry, a group of MIT scientists organizes an annual contest called iGEM, the International Genetically Engineered Machine compet.i.tion. Students can draw from the standard parts that the Registry contains, and perhaps contribute their own creations back to it. What kinds of "genetically engineered machines" do they build?

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A team of eight undergraduates from the University of Ljubljana in Slovenia-- cheering and leaping onto MIT's Kresge Auditorium stage in green team T-shirts-- won the grand prize earlier this month at the International Genetically Engineered Machine (iGEM) compet.i.tion at MIT. The group--which received an engraved award in the shape of a large aluminum Lego piece--explored a way to use engineered cells to intercept the body's excessive response to infection, which can lead to a fatal condition called sepsis. The goal of the 380 students on 35 university teams from around the world was to build biological systems the way a contractor would build a house--with a toolkit of standard parts. iGEM partic.i.p.ants spent the summer immersed in the growing field of synthetic biology, creating simple systems from interchangeable parts that operate in living cells. Biology, once thought too complicated to be engineered like a clock, computer or microwave oven, has proven to be open to manipulation at the genetic level. The new creations are engineered from snippets of DNA, the molecules that run living cells.10 45

Other iGEM entries have included E. coli bacteria that had been engineered to smell like wintergreen while they were growing and dividing and like bananas when they were finished, a biologically engineered detector that would change color when exposed to unhealthy levels of a.r.s.enic in drinking water, a method of programming mouse stem cells to "differentiate" into more specialized cells on command, and the mat of picture-taking bacteria I mentioned earlier.

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No matter how laudable the a.r.s.enic detector or the experimental technique dealing with sepsis, or how cool the idea of banana- scented, picture-taking bacteria, this kind of enterprise will cause some of you to shudder. Professor Drew Endy, one of the pioneers in this field, believes that part of that reaction stems from simple novelty. "A lot of people who were scaring folks in 1975 now have n.o.bel prizes."11 But even if inchoate, the concerns that synthetic biology arouses stem from more than novelty. There is a deep-seated fear that if we see the natural world of biology as merely another system that we can routinely engineer, we will have extended our technocratic methods into a realm that was only intermittently subject to them in a way that threatens both our structure of self-understanding and our ecosystem.

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To this, the synthetic biologists respond that we are already engineering nature. In their view, planned, structured, and rationalized genetic engineering poses fewer dangers than poorly understood interventions to produce some specific result in comparative ignorance of the processes we are employing to do so. If the "code" is transparent, subject to review by a peer community, and based on known parts and structures, each identified by a standard genetic "barcode," then the chance of detecting problems and solving them is higher. And while the dangers are real and not to be minimized, the potential benefits--the lives saved because the scarce antimalarial drug can now be manufactured by energetic E. coli or because a cheap test can demonstrate a.r.s.enic contamination in a village well--are not to be minimized either.

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I first became aware of synthetic biology when a number of the scientists working on the Registry of Standard Biological Parts contacted me and my colleague Arti Rai. They did not use these exact words, but their question boiled down to "how does synthetic biology fare in intellectual property's categories, and how can we keep the basics of the science open for all to use?" As you can tell from this book, I find intellectual property fascinating--lamentably so perhaps. Nevertheless, I was depressed by the idea that scientists would have to spend their valuable time trying to work out how to save their discipline from being messed up by the law. Surely it would be better to have them doing, well, science?

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They have cause for concern. As I mentioned at the beginning of this chapter, synthetic biology shares characteristics of both software and biotechnology. Remember the focus on reducing functions to black boxes. Synthetic biologists are looking for the biological equivalents of switches, valves, and inverters.

The more abstractly these are described, the more they come to resemble simple algebraic expressions, replete with "if, then"

statements and instructions that resolve to "if x, then y, if not x, then z."

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If this sounds reminiscent of the discussion of the Turing machine, it should. When the broad rules for software and business methods were enunciated by the federal courts, software was already a developed industry. Even though the rules would have allowed the equivalent of patenting the alphabet, the very maturity of the field minimized the disruption such patents could cause. Of course "prior art" was not always written down.

Even when it was recorded, it was sometimes badly handled by the examiners and the courts, partly because they set a very undemanding standard for "ordinary expertise" in the art.

Nevertheless, there was still a lot of prior experience and it rendered some of the more basic claims incredible. That is not true in the synthetic biology field.

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Consider a recent article in Nature, "A universal RNAi-based logic evaluator that operates in mammalian cells."12 The scientists describe their task in terms that should be familiar.

"A molecular automaton is an engineered molecular system coupled to a (bio)molecular environment by 'flow of incoming messages and the actions of outgoing messages,' where the incoming messages are processed by an 'intermediate set of elements,'

that is, a computer." The article goes on to describe some of the key elements of so-called "Boolean algebra"-- "or," "and,"

"not," and so on--implemented in living mammalian cells.

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These inscriptions of Boolean algebra in cells and DNA sequences can be patented. The U.S. Department of Health and Human Services, for example, owns patent number 6,774,222: 53

This invention relates to novel molecular constructs that act as various logic elements, i.e., gates and flip-flops. . . .

The basic functional unit of the construct comprises a nucleic acid having at least two protein binding sites that cannot be simultaneously occupied by their cognate binding protein. This basic unit can be a.s.sembled in any number of formats providing molecular constructs that act like traditional digital logic elements (flips-flops, gates, inverters, etc.).

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My colleagues Arti Rai and Sapna k.u.mar have performed a patent search and found many more patents of similar breadth.13 55

What is the concern? After all, this is cutting-edge science.

These seem like novel, non.o.bvious inventions with considerable utility. The concern is that the change in the rules over patentable subject matter, coupled with the Patent and Trademark Office's handling of both software and biotechnology, will come together so that the patent is not over some particular biological circuit, but, rather, over Boolean algebra itself as implemented by any biotechnological means. It would be as if, right at the beginning of the computer age, we had issued patents over formal logic in software--not over a particular computer design, but over the idea of a computer or a binary circuit itself.

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"By means of a computer" was the magic phrase that caused the walls around the public domain of algorithms and ideas to crumble. Will "by means of a biological circuit" do the same?

And--to repeat the key point--unlike computer science, biotechnology is developing after the hypertrophy of our intellectual property system. We do not have the immune system provided by the established practices and norms, the "prior art," even the community expectations that protected software from the worst effects of patents over the building blocks of science.

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Following the example of software, the founders of the MIT Registry of Standard Biological Parts had the idea of protecting their discipline from overly expansive intellectual property claims by turning those rights against themselves. Free and open source software developers have created a "commons" using the copyright over the code to impose a license on their software, one that requires subsequent developers to keep the source open and to give improvements back to the software commons--a virtuous cycle. Could the Registry of Standard Biological Parts do the same thing? The software commons rests on a license. But, as I pointed out in the last section, the license depends on an underlying property right. It is because I have automatic copyright over my code that I can tell you "use it according to these terms or you will be violating my copyright." Is there a copyright over the products of synthetic biology? To create one we would have to take the extension of copyright that was required to reach software and stretch it even further. Bill Gates might argue for intellectual property rights over software using the logic of his article in Dr. Dobb's Journal. Will the argument for copyrights over synthetic biological coding be "I need the property right so I can create a commons"?

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In practice, I think the answer is, and should be, no. Of course, one could think of this as just another type of coding, making expressive choices in a code of A's, C's, G's, and T's, just as a programmer does in Java or C??. Yet, software was already a stretch for copyright law. Synthetic biology strikes me as a subject matter that the courts, Congress, and the Copyright Office are unlikely to want to cram into copyright's already distorted outlines-- particularly given the obvious availability of patent rights. As a matter of conceptual intuition, I think they will see biological subject matter as harder to fit into the categories of original expressive writing. On one level, yes, it is all information, but, on another level, the idea of programming with gene sequences will probably raise hackles that the idea of coding inside a programming language never would. As a normative matter, I think it would be a poor choice to apply copyright to the products of synthetic biology. Attempting to produce a particular open commons, one might enable the kind of hundred-year monopolies over functional objects that the critics of software copyright initially feared.

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If one wishes to keep the basic ideas and techniques of synthetic biology open for subsequent innovators, there are alternatives to the idea of a synthetic biology open source license. The Registry of Standard Biological Parts or the BioBricks Foundation can simply put all their work into the public domain immediately. (This, indeed, is what they are currently doing.) Such a scheme lacks one key feature of open source software: the right to force subsequent innovators to release their code back into the commons. Yet it would make subsequent patents on the material impossible, because it had already been published.

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Regardless of the decisions made about the future of synthetic biology, I think its story--coupled to that of software and biotechnology more generally--presents us with an important lesson. I started the chapter with the metaphor of Procrustes's bed. But in the case of software and biotechnology, both the bed--the categories of copyright and patent--and its inhabitants--the new technologies--were stretched. Cracks formed in the boundaries that were supposed to prevent copyright from being applied to functional articles, to prevent patents extending to cover ideas, algorithms, and business methods.

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Until this point, though the science would have been strange to Jefferson or his contemporaries, the underlying issue would have been familiar. The free-trade, Scottish Enlightenment thinkers of the eighteenth and nineteenth centuries would have scoffed at the idea that business methods or algorithms could be patented, let alone that one could patent the "or," "if-then," and "not"

functions of Boolean algebra as implemented by a biological mechanism. The response, presumably, is to fine tune our patent standards--to patent the mousetrap and the corkscrew, not the notion of catching mice or opening bottles by mechanical means.

Still less should we allow the patenting of algebra. These are fine points. Later scholarship has added formulae, data, and historical a.n.a.lysis to back up Jefferson's concerns, while never surpa.s.sing his prose. As I said at the beginning of the book, if we were to print out the Jefferson Warning and slip it into the shirt pocket of every legislator and regulator, our policy would be remarkably improved.

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But it is here that the story takes a new turn, something that neither Jefferson nor the philosophers of the Scottish Enlightenment had thought of, something that goes beyond their cautions not to confuse intellectual property with physical property, to keep its boundaries, scope, and term as small as possible while still encouraging the desired innovation.

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Think of the reaction of the synthetic biologists at MIT. They feared that the basic building blocks of their new discipline could be locked up, slowing the progress of science and research by inserting intellectual property rights at the wrong point in the research cycle. To solve the problem they were led seriously to consider claiming copyright over the products of synthetic biology--to fight overly broad patent rights with a privately constructed copyright commons, to ride the process of legal expansion and turn it to their own ends. As I pointed out earlier, I think the tactic would not fare well in this particular case. But it is an example of a new move in the debate over intellectual property, a new tactic: the attempt to create a privately constructed commons where the public domain created by the state does not give you the freedom that you believe creativity needs in order to thrive. It is to that tactic, and the distributed creativity that it enables, that I will turn to now.

Chapter 8: A Creative Commons 1

If you go to the familiar Google search page and click the intimidating link marked "advanced search," you come to a page that gives you more fine-grained control over the framing of your query. Nestled among the choices that allow you to pick your desired language, or exclude raunchy content, is an option that says "usage rights." Click "free to use or share" and then search for "physics textbook" and you can download a 1,200-page physics textbook, copy it, or even print it out and hand it to your students. Search for "Down and Out in the Magic Kingdom"

and you will find Cory Doctorow's fabulous science fiction novel, online, in full, for free. His other novels are there too--with the willing connivance of his commercial publisher.

Search for "David Byrne, My Fair Lady" and you will be able to download Byrne's song and make copies for your friends. You'll find songs from Gilberto Gil and the Beastie Boys on the same page. No need to pay iTunes or worry about breaking the law.

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Go to the "advanced" page on Flickr, the popular photo sharing site, and you will find a similar choice marked "Creative Commons License." Check that box and then search for "Duke Chapel" and you will get a selection of beautiful photos of the lovely piece of faux Gothic architecture that sits about three hundred yards from the office where I am writing these words.

You can copy those photos, and 66 million others on different subjects, share them with your friends, print them for your wall, and, in some cases, even use them commercially. The same basic tools can be found on a range of specialized search engines with names like OWL Music Search, BlipTV, SpinExpress, and OERCommons. Searching those sites, or just sticking with the advanced options on Google or Yahoo, will get you courses in music theory, moral philosophy, and C++ programming from famous universities; a full-length movie called Teach by Oscar-winning director Davis Guggenheim; and free architectural drawings that can be used to build low-cost housing. At the Wellcome Library, you will find two thousand years of medical images that can be shared freely. Searching for "skeleton" is particularly fun. You can even go to your favorite search engine, type in the t.i.tle of this book, find a site that will allow you to download it, and send the PDF to a hundred friends, warmly antic.i.p.ating their rapturous enjoyment. (Better ask them first.) 3

All this copying and sharing and printing sounds illegal, but it is not (at least if you went through the steps I described). And the things you can do with this content do not stop with simply reproducing it, printing it on paper, or sending it by e-mail.

Much of it can be changed, customized, remixed--you could rewrite the module of the cla.s.s and insert your own ill.u.s.trations, animate the graphs showing calculus in action, morph the photo into something new. If you search for a musician with the unpromising name "Brad Sucks," you will find a Web site bearing the modest subt.i.tle "A one man band with no fans." Brad, it turns out, does not suck and has many fans. What makes him particularly interesting is that he allows those fans, or anyone else for that matter, to remix his music and post their creations online. I am particularly fond of the Matterovermind remix of "Making Me Nervous," but it may not be to your taste.

Go to a site called ccMixter and you will find that musicians, famous and obscure, are inviting you to sample and remix their music. Or search Google for Colin Mutchler and listen to a haunting song called "My Life Changed." Mr. Mutchler and a violinist called Cora Beth Bridges whom he had never met created that song together. He posted a song called "My Life" online, giving anyone the freedom to add to it, and she did--"My Life."

Changed.

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