Steal This Genome! 

Inspired by a group of free-thinking Berkeley scientists, a movement is afoot to return biology to the public realm.

Somewhere along the line, biologists started describing their research with words related more to machines than living things; DNA was a "blueprint," a "code," even an "operating system." The US Supreme Court further extended the metaphor in 1980 by ruling that biologists could patent living organisms. The decision kicked off a quarter-century of life-science commercialization that, while yielding significant advances, has closed many doors of innovation to those who couldn't handle the cover charge. Now, a fledgling movement of scientists alarmed by the commercialization of basic research is striking back with its own computer metaphor: open-source biology.

In programming jargon, "open-source" refers to a form of software licensing that lets anyone copy and modify an application's source code. The Linux operating system and Web browser Firefox, for instance, are open-source alternatives to Microsoft's market-dominating products.

Prior to the 1980s, basic life-science research was already open-source, except nobody thought of it in those terms -- investigators simply built on the discoveries of others. But as scientists unravel entire genomes in this age of DNA sequencing, the old ways no longer apply. Reviving them, in practice, would require that researchers willingly make their discoveries publicly available under some kind of open-source license.

This past December, the journal Public Library of Science Medicine published a paper demonstrating how, under such an arrangement, off-duty biologists could work together to find cures for tropical diseases in their spare time. That may sound like a bad classified ad, but the concept is dead serious. These volunteers would wade through oceans of open-source data on pathogens, searching for familiar proteins and identifying chemicals -- drug candidates -- that might bind to them.

Stephen Maurer, a Cal economics professor and lead author on the paper, thinks biologists would do this for the same reasons many programmers spend their free time searching for bugs in computer software and writing open-source patches to fix them. He envisions scientists who work on the next antibalding pill at big drug companies by day logging on to a "virtual pharma" in the evenings to tease out the makings of a cheap dengue fever vaccine.

Open-source advocate Richard Jefferson, a biologist at the nonprofit Cambia research center in Canberra, Australia, validated the concept in February by publishing a discovery that he hailed as an alternative to a crucial patent-protected process. Biotech giants Monsanto and Syngenta have long controlled the rights to the best methods for hacking plant DNA, which employ the soil microbe Agrobacterium tumefaciens as a Trojan horse to deliver new genes into plants. Jefferson, reportedly a descendant of America's third president -- who, ironically enough, was a key architect of the nation's patent system -- developed his method using nonpatented bacteria as a DNA courier. Besides being free, it improved upon the existing tools: The patented methods make plants sick. The new technique does not.

The expression "open-source biology" was coined in the late 1990s by Drew Endy of Berkeley's nonprofit Molecular Sciences Institute, an independent research facility. At the time, debate was raging over attempts to patent arbitrary DNA sequences -- barely discoveries, and certainly not innovations. Endy saw how things were playing out: Rather than contribute to the burgeoning body of genetic knowledge, companies doing basic research were restricting access to crucial parts of the human genome thought to contain genes implicated in a host of diseases. He responded by creating a "BioLinux" Web page. "Since we ourselves depend on the information encoded in genetic material," he explains, "we should work together to share genetic information."

Endy is an engineer by training, and his research had nothing to do with intellectual property theory, but MSI is the kind of place where people are encouraged to think big. Shortly after launching the institute in 1996, renowned geneticist Sydney Brenner had challenged his crew to identify the key sticking points to scientific progress, and come up with ideas to circumvent them. Brenner -- who shared the 2002 Nobel Prize for medicine -- was asking them, in essence, to help him shape the future of science. It was a galvanizing charge.

At the time, Endy was living in the hills above the Claremont Hotel with fellow institute scientist Robert Carlson and administrator Lauren Ha in a house of concrete and glass that Carlson dubbed "the palace." The three would stay up late and exchange ideas while taking in the city lights below. "We did nothing but eat, sleep, and talk institute," Ha recalls. "None of us really had lives outside of work."

When the three presented the idea of open-source biology to senior institute scientist Roger Brent, he took to it wholeheartedly. The group began spreading the gospel. The proprietary system, Carlson and Brent argued in a letter seeking funds from the Defense Advance Research Projects Agency, was bogging down science and restricting competition. "We think it would be a shame if, in 2009, most of the wheat in this country was dependent on an operating system of the quality and stability of Windows 95," the pair wrote.

They also made a plea on behalf of public safety; there's no way any federal law can ensure that someone doesn't create an organism that, as Brent puts it, "liquefies Cincinnati." Rather than trying to keep secret, for example, the genome of a potential bioterror agent, the institute crew concluded that it's better to empower as many people as possible to develop countermeasures such as new drugs and vaccines. "Consider that the only effective counterterrorism measures on September 11, 2001 were made by the passengers of Flight 93," Brent says.

Carlson, Endy, and Brent all agree that the best way to keep tabs on the potential dangers brewing in labs was to share information. "The only way the shit doesn't hit the fan is if everybody engineering biology does so in the open," Endy says. "We're co-opting the idea from open-source software that 'many eyes lead to few bugs.' In other words, I don't trust you not to make any mistakes the next time you program a piece of DNA. You shouldn't trust me."

The institute crew has since dispersed, but its members are still pushing their brainchild and working with Columbia University law professor Eben Moglen to create an open-source license for biological innovations. Meanwhile, people like Maurer (with his virtual-pharma scheme) and Jefferson (with his open-source gene transfer method) are contributing to the cause. Then there's the Public Library of Science itself, a nonprofit publishing house that posts its journal contents online for all to see. It was cofounded by a Cal researcher as part of a recent backlash to the exorbitant subscription rates charged by for-profit journals, which many scientists felt were limiting access to the results of publicly funded research (see "Publisher for the People," feature, 9/29/04). Following this example, the National Institutes of Health, which finance the majority of basic research in the United States, recently ordered science publishers to put articles based on publicly funded research online within six months of publication.

Endy takes no credit for any of this -- open-source biology was simply a concept whose time had come, he says. To wit, at a 2000 genomics conference in Tucson, a number of engineers and authors approached Carlson to comment on an award-winning essay he had written, predicting what the world would look like in 2050. "The engineers present thought my 'World in 2050' essay was great, while the science-fiction authors considered the ideas old news and inevitable," Carlson says. "So you could argue either that we were on the cutting edge or that we were merely fleshing out the inevitable."

In the old days, all biology was "in vivo" -- in life. Then scientists learned how to grow organisms "in vitro" -- in glass. Now biology is "in silico." Computers have become as necessary for molecular biology as test tubes. Yet open-source is still an imperfect metaphor for the life sciences. Notably, it costs significantly more to do wet-lab research than to write code. But the scientists are working on this, too, looking for ways to frame their idea within the context of economic realities. So far, though, the movement has but served as a small, spunky alternative to the corporate giants, pushing them, its visionaries hope, to do better.

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