Creation (18 page)

Given that our dreams of establishing permanent bases on other worlds are profoundly hindered by having to carry the building materials from Earth, using the materials on another planet is appealing. The question is, can we build with moon dust?
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The Brown-Stanford iGEM team founded their project on this question. They happened upon the alkali-loving bacteria
Sporosarcina pasteurii,
whose metabolism involves expelling the mineral calcite as a waste product. In the right type of sand this undergoes a process called biocementation, that is, it forms cement. Water in normal concrete forms a sort of glue by a range of chemical reactions and is used up in the process. The cells that secrete calcite can serve this purpose without water, other than what they need to live. The key component of this process is a protein called urease, which initiates the breakdown of urea, and in these bacteria ends with cementation outside the cell. The iGEM team identified the genetic circuit for urease production in
Sporosarcina
and copied it into a standard lab cell,
E. coli
. They then characterized and standardized it into a BioBrick part, where it became known as Part: BBa_ K656013. When expressed in a cell, and placed in regolith, the circuit is activated and has the ability to cement it into bricks. They have tested this process using simulated Mars sand, admittedly in molds less than half an inch across, but within a few hours they solidify into tiny bricks. Clearly, this is an astronomical distance from being used as a building material on Mars itself; that journey is at least a decade away, but at the rate synthetic biology is progressing, making actual bricks from Martian regolith becomes a whole lot more plausible. True to the playful roots of the BioBricks project's mentality, they are called REGObricks. The weight saving is enormous. A small vial of these remixed cells could be transported aboard a ship weighing only a couple of grams, then grown into a REGObrick factory on the planet itself.

These are just a handful of some of the hundreds of entries to the iGEM competition during its first decade of existence. The BioBricks Foundation aims not just to spread the potential of applying engineering principles to biology, but to do it in a way that fosters open, egalitarian science, creativity, and a free exchange of creativity, much like the remix musicians in the 1970s and '80s.

While this may sound somewhat idyllic, there are problems with iGEM and the BioBricks Foundation. In terms of bearing fruit, more often than not, iGEM teams do not actually deliver the products they have designed, often due to the time constraints of the competition (though many individual parts and circuits have resulted in published scientific papers further down the line). But there are plenty of other issues with the BioBricks Foundation. Hundreds, if not thousands of the parts in the registry are not well characterized. The individual parts include genes as well as the instructions to turn genes on or off. But many of these behave inconsistently or unpredictably, and much of this may be to due to the biological noise of a living cell, as compared with the logic diagram on a design. The nature of the competition means that students often don't have time to fully characterize the parts they have built. Standardization is becoming a Sisyphean task, with the rate of submissions overwhelming the urgent task of characterizing what is already there.

Nevertheless, the excitement of the competition is electric. Teams contain students from backgrounds in math and engineering as well as from the biological sciences, and bring a fresh ignorance to the problem solving. I went to the UK team meet-up in September 2012, organized by the University of East Anglia's team leader, Richard Kelwick. The UK entrants presented their projects to one another and a handful of synthetic biologists in anticipation of heading off to Amsterdam to be selected for the world finals. Out of eighty-five students entering from the United Kingdom, twenty-nine were not biologists. The entry level for some of the most sophisticated, creative, and advanced genetic engineering is as open as it has ever been. Of the three teams that went through to the next round, University College London's project was the most outlandish, literally: bacteria that would collect and consume the billions of tiny fragments of non-biodegraded discarded plastic that float in the oceans, with the intention of using this harvest to build a plastic island, recycled and claimed from the sea.
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Open access is deliberate and inherent in the BioBricks mentality: a profound understanding of how biology works is not necessary if you are to use that biology merely as a tool. While this may seem at first glance questionable, it is how we operate with all technology. I type these words onto the keyboard of a computer whose hardware is largely mysterious to me, using software written in a language as foreign to me as Mandarin. Even the simplest mechanical tool, such as a monkey wrench, is made by a process that requires expertise unknown to most people who use it. With the application of engineering principles to biological components, the question is not how these parts work, but whether they work. This way, biology becomes nonexclusive. By standardizing the parts, the entry-level criteria are lowered past the point where traditional DNA expertise is required. Paul Freemont runs the Centre for Synthetic Biology and Innovation, Europe's largest synthetic biology department, at Imperial College London (which will host the biannual premier synthetic biology meeting in 2013 called SB6.0). He told the BBC in 2012 that they have “a whole load of new people coming in, young, energetic researchers. They don't care where the biology is, they just want to build things [and] they want to solve problems. They don't have any baggage.”

Who Owns Your Creation?

Because the purpose of synthetic biology is to create solutions for real-world problems, the potential for commercialization is obvious. Inevitably, the question of ownership looms over any components, devices, and products that get made. The story of patents and DNA is a tortuous and ongoing one, messy not least of all because the laws regarding patenting were not designed with biotechnology in mind. The promise that synthetic biology holds for future technologies means that the question of patents is intrinsically entwined with the science, and may yet have an effect on how this necessarily creative industry will flourish. Therefore, it's worth having a mercifully brief look at the problems.

Patents are historically designed to protect useful functional inventions, whereas copyright protects the physical expression of an idea—be it in the form of a written or music manuscript, a photograph, or a web page—by granting ownership, usually to the creator. But more fundamentally, both copyright law and patents were introduced in the United States in order to foster creativity for the greater good. Inventors need protection over their creations, as the time, money, and intellectual investment they put into designing and making a new product is considerably greater than is required for simply copying it.

So-called products of nature, on the other hand, are ineligible for patents, as they occur without any human ingenuity. Yet it has been successfully argued that once a genetic sequence, such as a gene, is isolated and characterized, it is no longer a product of nature, as it has been copied and subjected to the intervention of humans. Therefore, it can be protected by a patent. The most high-profile recent test case of DNA ownership was (and continues to be) for two breast and ovarian cancer genes, BRCA1 and BRCA2, both of which are owned by the company Myriad Genetics and the University of Utah Research Foundation. At the time of this writing, this case has been bounced back to the Federal Supreme Court in the United States on the grounds that the techniques applied to isolate the DNA are standard molecular biology and not unique. The back-and-forth about DNA patents rumbles on. Nevertheless—primarily using the argument that the isolation of genetic sequences is a process—currently one in five human genes, the genes that you carry around in your cells, are effectively owned by someone else.

When it comes to patenting living things, the law, at least in the United States, is marginally clearer. The first patent on an organism was upheld in 1980, with a genetically modified bacteria that helped break down crude oil. It was granted, on appeal, on the grounds that its genes were at least partially man-made, and that the process of manufacture was patentable. The key phrases used in the ruling were that the invention (and therefore the patent) constitutes a “manufacture” or “composition of matter.” In 1988, this was extended to a multicelluar organism: the OncoMouse is a transgenic mouse whose DNA has been modified to make it particularly susceptible to various cancers, and therefore is a valuable research tool. And in 2010, Craig Venter filed a patent for the genome of his artificial cell Synthia.

Because the products of synthetic biology have little historical precedent, it is not yet clear how the law will (or will evolve to) handle them. In this case the complexities of DNA patenting highlighted above are compounded by the fact that much of the thought and, indeed, behavior behind synthetic biology components resembles, often by design, computer software. It gets even murkier here, as software is a field also beset by continual messy ownership debacles. Software falls somewhere between patent and copyright, as it is both functional (it enacts a program) and an intangible work (it is written to be enacted). The behavior and use of individual parts or pieces of software source code, such as formulas and calculating machines, can change depending on how they are used. As a result, computing patents are sometimes bafflingly broad, encompassing very nonspecific terms.

My wading into this dark world of intellectual property has specific relevance to the nature of the BioBricks part. As a result of the nebulous legality of biotechnology, broad patents have been used to grant intellectual property rights over mechanisms of basic cellular machinery. They cover general principles as well as specific processes. This has the effect of restricting experiment on those cellular activities, especially for researchers at the beginning of their careers, who might not be able to afford to pay for patented processes. If broad patents could be applied to the devices that synthetic biologists have created, such as over an oscillator in a generic sense, then it could potentially limit modification of what has become a basic instrument in the synthetic biology toolbox.

The BioBricks Foundation has recognized these potential pitfalls and taken a very precise stance on them. They state that its mission is “to ensure that the engineering of biology is conducted in an open and ethical manner to benefit all people and the planet. We believe fundamental scientific knowledge belongs to all of us and must be freely available for ethical, open innovation.” They have reflected that patenting and copyright law as applied to computing was riddled with inadequacies. The BioBricks Foundation user agreement has enshrined an irrevocable protection from the assertion of intellectual property rights. Attribution to the creator and adherence to safety practices and, naturally, the law, are part of the agreement, but the part itself is quintessentially free to use. By placing their wares in the public domain, the users are precluding the possibility of thickets of patent enforcement, and consequently encouraging innovation and creativity.

In April 2012, recognizing the potential that synthetic biology has to change the world, President Barack Obama launched the National Bioeconomy Blueprint, a roadmap of how to invest in synthetic biology in order to extract the maximum benefit from it. This plan has commercial development written into it, but also recognizes the value of the BioBricks Foundation's core beliefs about sharing data and resources. Very specifically, this set of recommendations is designed to promote growth in synthetic biology, address safety issues, encourage commercialization without restricting creativity, and ensure the public is coming along for the ride.

The protection of creativity is enshrined in the titles of patent and copyright legislation, both from 1790: the Copyright Act is subtitled “An Act for the encouragement of learning” and the Patent Act's mandate is “to promote [. . .] useful Arts.” In music, computing, genetics, and potentially the newcomer synthetic biology, these principles have been mired in the wake of speedy technological advances that far outpace changes in the law. As a result, in biotechnology, patents are in danger of becoming the embodiment of the impediment of creativity. When that happens, progress halts.

Again, the parallels with music are striking. Sampling in recorded pop music has become virtually ubiquitous. Hip-hop, which is based inherently on sampling, grew to become the biggest and most dominant business in music. As corporations recognized its immense commercial potential, the companies that owned copyrighted music also began to exercise and enforce control over the sampling on which hip-hop and other music genres were based. Copyright laws were refined and introduced; the upshot is that unless you have deep pockets, nowadays it is virtually impossible to make music with the same creative freedom that helped define this genre.

For synthetic biology, wrangling with this tangled legal thicket is all part of the rapid maturation of a very young field. In 2011, one of its godfathers, Drew Endy, opened a new venture to provide support and an open legal framework for the continued development of biological devices, circuits, and tools. At the launch he declared that “[w]e now need to move beyond Lego metaphors and genetic toys to professional technologies.” The message is that synthetic biology needs to mature, both scientifically and legally, and to become the global industry its founders think it can be. Yet it should also continue to be fueled by unbridled creativity and even playfulness, as this is the fertile ground from which the most innovative ideas grow. In the words of the Harvard law professor and copyright activist Larry Lessig, “A culture free to borrow and build on the past is culturally richer than a controlled one.”