While DARPA’s best known for its research on technologies with national security applications, the agency has a strong track record of producing innovations with transformative civilian applications as well. From the Internet, to GPS, to driverless cars and robotic limbs, DARPA-initiated research has often made big if not revolutionary splashes in the marketplace. To quote Jackson, “we [at DARPA] are that genie in a bottle that will make the impossible inevitable.”

In the fields of synbio and bioengineering, scientists introduce new genetic information into microorganisms to coax them into producing useful products. These fields have already made significant strides in the production of some pretty incredible chemicals and materials with applications in agriculture, industry, pharmaceuticals, and more. Recent accomplishments include using microorganisms to produce the anti-malarial drug artemisinin, renewable petroleum, steel-strong spider silk, and even whole battery electrodes and solar cells.

Research agencies across the federal government have shown increasing interest in funding synthetic biology research in recent years, including $700 million from the Department of Energy between 2006 and 2010, $40 million from the National Science Foundation in 2010, and at least $48 million from the National Institutes of Health between 2005 and 2010. Even the Department of Agriculture has put $2.3 million into synthetic biology research in recent years. DARPA’s past work in synthetic biology includes modifying the genome of the tobacco plant to produce vaccines as well as a program to engineer immortal microorganisms with genetically-coded kill switches.

Despite increasing attention to synthetic biology in federal agencies and the research community, research is “…limited to producing only a small fraction of the vast number of possible chemicals, materials, and living systems that would be enabled by the ability to truly engineer biology,” says the Living Foundries funding announcement. The Living Foundries program hopes to set itself apart from traditional synbio research projects and transcend the “ad hoc, laborious, trial-and-error” efforts of the past by investing in platform research that can support a broad range of applications, bring down cost, and increase scale. This approach to research on the process of biomanufacturing itself rather than on the production of specific and siloed chemical outputs DARPA dubs “engineering biology.”

DARPA’s vision for engineering biology is ambitious. The Living Foundries project proceeds from the assumption that modular genetic parts can be “mixed and matched on demand” to create a broader array of chemicals and materials more efficiently. This is perhaps conceptually similar to the introduction of interchangeable parts that transformed manufacturing in the late 18^th century, except on a genetic level. Lena Groeger of Wired.com likens the rearrangement of “modular genetic parts” at the core of the Living Foundries’ research to the way that children play with Legos.

Potential grant recipients, including 170 businesses and a number of academic and government research teams, attended a daylong event on June 28 where DARPA advertised its vision and goals for the program. Having received proposals from academic and corporate research groups, DARPA is now taking the next step of determining winners. Once funding decisions are made, DARPA plans to have projects running over the next three years and to see tangible results by the end.

At a time of sluggish economic recovery and stiff international competition, DARPA’s decision to invest in research with broad potential applications in medicine, energy, agriculture, and consumer products as well seems wise. The initial stage has been set, and the next few years will show whether the program’s goals come to fruition. If so, American manufacturing may witness a new milestone.

Gaurav Dhiman is a former intern with the Science Progress team and a rising senior majoring in biology and political science at the University of Miami.

The commission has moved quickly since its inception last July to produce a farsighted report on the opportunities and ethics of synthetic biology and emerging technologies in December. In forming the commission the president asked experts to:

• “Review the developing field of synthetic biology
• “Consider the potential medical, environmental, security, and other benefits as well as potential health, security, or other risks
• “Identify appropriate ethical boundaries to maximize public benefits and minimize risks”

Speakers were Nelson Michael, M.D., Ph.D., a member of the commission and director of the Division of Retrovirology at the Walter Reed Army Institute of Research; and Valerie Bonham, J.D., executive director of the commission.

Because of the still emerging nature of this technology, Dr. Michael said, the commission had the “rare and exceptional opportunity to be forward looking instead of reactive,” to “take a deep breath and have a public dialogue.” In other words, it is better to begin to identify where future opportunities and threats may lie as new industries develop rather than to try to address them once entrenched interests have taken root.

Synthetic biology is the application of engineering principles to organisms and biological systems. The president’s formation of the commission was in response to last year’s announcement that Craig C. Venter had rebooted a single celled organism with an entirely synthetic genome. Dr. Michael pointed out that this process cost roughly $40 million and occupied a whole research team, but the feat caught the world by surprise and triggered a national debate.

There is a debate about whether Venter’s achievement specifically—and synthetic biology more broadly—are revolutionary in science, or merely an evolutionary extension of molecular biology and genetic engineering. According to Dr. Michael, “molecular biology was intended to ask questions and interrogate biological systems, whereas synthetic biology takes a different approach…While [it] sits on the shoulders of those that came before,” what is unique about synthetic biology, he continued, is that “synthetic biology seeks to make useful things.”

What kinds of useful things? Some of most promising near-term applications of the technology include more effective and efficient production of vaccines, environmentally friendly biofuels, and improved pharmaceuticals. For example, the chemical Artemisinin is a powerful antimalarial that currently must be extracted laboriously and expensively from the sweet wormwood plant. The hope is that pharmaceutical companies could use synthetic biology to engineer microbes to produce large amounts of this chemical in a form that is easy to refine, leading to a more affordable production technique for the life-saving drug. Similarly, researchers working in energy are hoping to use synthetic biology to engineer fuels from sunlight at the Department of Energy’s energy innovation hub at Lawrence Livermore. Using synthetic biology, researchers are experimenting with the genomes of algae species to produce high quantities of lipids for easy conversion to fuel.

But these possibilities are just the beginning. As with any emerging field of technology, where it will lead is difficult to predict. In one famous example of innovators failing to see the long-term implications of their technologies, Thomas John Watson Sr., the president of IBM Corporation in the 1950s supposedly said he believed there would be a world market for “maybe five computers.” Today there are about a billion computers worldwide. While it is unclear whether Thomas John Watson Sr. ever actually uttered those words, we do know that IBM Corporation suffered for its myopic focus on hardware and for failing to predict the vast and growing market for software that their innovation would create. If there is anything we know about technological innovation, it is that it is unpredictable.

Nonetheless, there are some common questions that we should ask of any new field, even if we do not know what it will look like in five, 10, or 50 years. The commission members and staff at the event on Thursday also noted that the report has implications for assessment of all emerging technologies. The report advocates that for synthetic biology and any emergent field of technology, policy needs to be guided by the principles of public beneficence, responsible stewardship, intellectual freedom and responsibility, democratic deliberation, and justice and fairness.

In investigating these principles for policy on synthetic biology, the commission engaged with leaders from the science, faith-based, legal, and ethics communities to evaluate potential risks, and created 18 principles for maximizing the public good. They also took a number of public comments, according to the commission’s executive director, Valerie H. Bonham, to ensure that they gathered “opinions from broad swath of society, on both technical and scientific issues and ethical concerns.” The results are a sensible balance between the “let science rip” approach—for example, minimal regulation to allow maximum progress, but also maximum risks—and an extremely measured regulatory approach that minimizes risk but also slows progress.

The president’s commission’s active engagement with stakeholders should serve as a model for the assessment of risks and benefits of new technologies.

You can view the event video and summary here, and you can download the commission’s report here.

Jonathan Moreno, Ph.D., is the Editor-In-Chief of Science Progress and a Senior Fellow at the Center for American Progress. Sean Pool is the Assistant Editor of Science Progress.

The promise of the field of synbio as a whole is that scientists will be able to employ this type of genome synthesis to create customized life forms for a wide array of purposes. The peril is exactly the same as the promise.

Rising to this demanding task, committee chair Amy Gutmann, president of the University of Pennsylvania, led a constructive conversation by asking pointed questions and periodically distilling the major points of contention and agreement among the various discussants. Drew Endy of Stanford University, a pioneer of synthetic biology, praised the meeting as the best conversation on synthetic biology that he has ever seen. The reason, he said, was that the most striking development over the course of the two-day conversation was its shift from simply avoiding the risks of synthetic biology to carefully harnessing its benefits in a way that is attuned to broader global challenges.

Jim Thomas of the ETC Group, a Canadian green civil society organization, prompted this major turn in the conversation towards synbio’s global socio-economic implications by emphasizing the economic displacement that takes place when a new technology like synthetic biology enters the global economy. For instance, a synbio technology that allows an industry to grow an organic product in a vat for a lower cost than it could on the land would destroy the livelihood of thousands of farmers the world over. Thomas’s position was distinctly green and scientifically prohibitionist since he advocated a moratorium on the commercial or environmental release of synthetic biology products.

Indeed, upon further questioning by the commission, it seemed as if he were advocating more of a ban than a moratorium since he could not arrive at a concrete “bottom line” for the safety and equity standards that synbio would have to meet for the moratorium to be lifted. He suggested the creation of new “social technologies” for assessing the social and economic impacts of technology and building democratic consensus among global populations. He noted that there is currently no democratic way of allowing the release of synbio technology, to which Dr. Gutmann retorted that there is no democratic way of banning it either.

The dialogue prompted Allen Buchanan of Duke University to provide a more tech-positive counterpoint to Thomas’s claims about the vulnerability of the global environment. Buchanan argued that objections about “playing god,”  “interfering with nature,” or “altering human nature” are often used to smuggle in assumptions about nature being inherently harmonious, stable, or balanced.  He explained that nature is in a constant state of flux and that evolution is an imperfect process that “at most…fleetingly approximates maximal biological fitness.”

Assumptions about nature being benign or harmonious automatically stack the deck against any biotechnologies. Since risk can never be completely eliminated, Buchanan encouraged the commission to educate the public about risk management, its costs, and the importance of institutional designs that create the incentives for accurate risk management. And he did agree with Jim Thomas’s suggestion that effective institutions will require the development of new “social technologies.”An emphasis on social technologies seemed to appeal to the commission and many of the presenters as a new frontier for promoting scientific innovation in a way that is safe, responsible, and democratically accountable without over-relying on top-down regulation.

More controversially, Buchanan clarified the meaning of “dual use” by subdividing it into two types. The more commonly understood form of dual use is the possibility that terrorist groups or rogue states could misuse a technology like synbio, but Buchanan also proposed that “good” actors or states could use synthetic biology for offensive purposes in the name of defending themselves. As an example, he pointed to the grossly unethical human radiation experiments perfumed by the U.S. government from 1944 to 1973.

Buchanan concluded by encouraging the commission to focus on these concrete risks and benefits and not get bogged down with more intrinsic unanswerable questions about human nature, the meaning of life, or the implications of biological materialism for human moral agency. He was clearly asking for the commission to be decisively pragmatic in its recommendations for managing the risks and benefits of synbio without completely ignoring various theoretical views and approaches.

During the audience Q & A period, Gerald Epstein of American Association for the Advancement of Science reminded the commission that synbio will only be one component of much larger issues that humanity faces and that and it should try to analyze the implications of synbio for social justice, human security, or the environment “as a whole.” These discussions moved the conversation toward an emphasis on concrete risks and benefits of synbio for a diverse and complex global environment.

The second day of the meeting continued to place synthetic biology in this broader context. Paul Wolpe of Emory University reminded the commission that humans create technology that then goes on to recreate human existence—examples of this range from the plow, to the car, to the Internet. He speculated on the numerous effects that synbio can have on human lifestyles and humankind’s conception of itself, but he eventually zeroed in on the contrast between the value that humans place on speed and the human impulse to respond to technology incrementally.

Synbio will increase the speed of various biological processes, but humans will only come to understand it incrementally, not realizing the transformative potential of the technology until it has actually transformed our lives. It is this fear of incremental steps toward an irrevocable transformation of human existence that has underpinned some of the behavior-based religious systems and even the “playing god” objection. Wolpe recommended that the commission address synbio in “a positive way by creating goals and incentives rather than trying to stop things.”

He also cautioned that this positive view of synbio’s capabilities be tempered with a wisdom that avoids fetishizing science by over-relying on arguments based on utopian visions or a hyperbolic sense of urgency. So, not only must the commission focus on managing concrete risks and benefits in a global environment, it must understand those risks and benefits in terms of the diverse cultural and religious values held by many of the world’s populations. The commission must also be humble enough to understand that common beliefs about the beneficent power of science and society’s ability to grapple with its implications as possessing their own biases and limitations.

This line of discussion made the meeting as a whole very productive. It elucidated many of the most compelling arguments for a positive, risk management-based, globally-contextualized, culturally self-aware, and pragmatic approach. By coupling this approach to the specific safety and oversight concerns of scientists, business leaders, government officials, and everyday citizens, the commission can find a way to be open to various views of scientific progress while also being critical of them as it makes concrete recommendations. This is what a bioethics commission should be doing, paving a confident path through the ethical forest while respecting the great variety of the trees.

Michael Rugnetta is a Research Assistant to Jonathan Moreno for the Center for American Progress’s Progressive Bioethics Initiative and Science Progress.

• advance our understanding of basic biology
• create new vaccines, drugs and diagnostic tools
• repair diseased tissues
• engineer new carbon-neutral energy sources
• provide countermeasures for polluting environmental toxins

Synthetic biology, or “synbio,” is a relatively new laboratory discipline that involves creating or altering new life forms. The basic tools of synbio are standard biological parts—sets of genes and chromosomes with known and specific functions created in modern biology labs—that can be assembled to program cells and control an organism’s functions. The process resembles computer programming in that scientists assemble blocks of genetic “code” into instructions for tiny cellular machines.

“Biobricks” are standard, interoperable pieces of DNA for genetic engineering. They are already widely available from commercial websites and the relevant skills for creating them are known to any reasonably competent biology graduate student. Taking advantage of rapid advances in gene sequencing, even college students are learning the techniques. Engineers use biological parts like genes, proteins, and portions of chromosomes to build new microscopic organisms that behave in certain ways. Synthetic biology is only in its infancy, and it will likely be combined with such other emerging fields as nanotechnology to create entities that blend the mechanical and biological.

Synbio nonetheless raises a wide variety of issues that will need to be addressed through a combination of monitoring and regulatory measures, without inappropriate restrictions that block innovation. These issues include:

• Potential environmental hazards due to the accidental release of man-made organisms that may turn out to be harmful and difficult to eradicate
• The possibility that treatment-resistant bacteria or viruses could be synthesized for use in biological warfare
• The risky combination of portions of genes from a human source with those from a non-human source, whether biological or non-biological

For other reasons individuals across the social and political spectrum may also find synbio intrinsically objectionable. The matters of potential cultural concern are far more complex than those faced in the stem cell debate. Many will not view the creation of new life forms capable of performing specific tasks as morally neutral. Political realignment around “naturalness” is a phenomenon that has become familiar in other areas, such as human cloning and genetically modified organisms. A similar reaction could apply to synthetic biology as its implications enter popular awareness.

These worries need to be addressed with seriousness and candor. Scientists and investors rightly complain that inappropriate regulation can impair the development of a new field, yet the rise and fall of public interest in and support of gene therapy should serve as a cautionary tale. Experience has shown that a single adverse event can have an enormous impact on public perception. Ever since the French Enlightenment, trust in scientists has been a crucial component of public support of scientific and technological innovation.

Governance of biotechnology has several elements. Self-policing by the scientific community is necessary but not sufficient. In this field there is an irreplaceable role for smart government, but authority for oversight and regulation of synbio in the United States is currently at best a partial patchwork. The National Institutes of Health require labs receiving its funds to comply with Recombinant DNA guidelines; the Food and Drug Administration would have to approve a drug created by synbio; and the Department of Agriculture might be responsible for avoiding the environmental release of synthetic organisms. But current regulations may not address unique risks posed by the technology.

Nor will merely domestic arrangements be enough. The context for the scientific and commercial interest in the field is a research and development system that has in the past decade or so become globalized to an unprecedented degree. International cooperation and continued scrutiny at many levels of government will be required, as technology will almost certainly rush ahead of current conventions. Researchers and their supporters should also seek innovative approaches for verifying the character and safety of new life forms created through synbio.

Over the long term, the social and scientific impetus behind synthetic biology will overcome political posturing. The greater danger is that through overreaction and misunderstanding we could miss an early opportunity to engage in careful assessment of the research and the development of improved or new regulatory models to avoid harms and maximize the potential benefits of synbio for the common good.  The industrial platforms that this technology is helping to develop will be key components of prospering national economies and national security systems over the next fifty years. America can and must be among the leading innovators.

Jonathan D. Moreno, Ph.D., is the David and Lyn Silfen University Professor of Ethics and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania, and the Editor-in-Chief of Science Progress.

More on synthetic biology from Science Progress:

Ribosomes Rising: Synthetic Biology Accelerates
By Jonathan D. Moreno

Synthetic Biology: An Overview and Recommendations for Anticipating and Addressing Emerging Risks
By Denise Caruso

All Together Now: As Emerging Technologies Converge, So Should Ethical Discussions

Interview: David Deamer Explains Synthetic Life: Unpacking the Latest Advance in Biology
Interview by Andrew Plemmons Pratt

So if citizens aren’t familiar with a technology that researchers currently use to create antimalarial drugs and that major players in the energy industry want to use to churn out biofuels, you just tell them more, right? As Huston Chronicle science reporter Eric Berger points out, not necessarily. “Surprisingly — and this should sober scientists in the field — when the poll respondents were told more about synthetic biology, they became more concerned,” he observes.

The approach explained in the survey report is what science communication experts call the “deficit model”: explain how a scientific process works and hope that people will get behind it when they know more. As Rick Borchelt and Kathy Hudson explained here at SP:

The basic assumption behind these models is that there is a linear progression from public education to public understanding to public support, and that this progression—if followed—inevitably cultivates a public wildly enthusiastic about research. But this model of scientific engagement with the public obviously isn’t working.

The survey doesn’t argue for generating public support for synthetic biology by pursuing a deficit model, but its findings, as Berger makes clear, demonstrate the problems with the approach. In fact, after hearing a short explanation about the potential benefits of synbio (treating disease and cancer, generating renewable energy, reducing pollution) and the risks (unknowns, potential pollutants bioweapons, and ethical concerns), listeners often decided that the risks will outweigh the benefits:

Looking at the survey and the recent New Yorker article on synbio side-by-side is a useful demonstration of how a concrete narrative can present the benefits of an emerging technology in an easy-to-grasp and positive light. Michael Specter ‘s story opens with a history of how scientists developed artificial artemisinin, a powerful treatment for malaria strains that are resistant to other drugs. The development of bacteria that manufacture the compound is considered the poster-child example of synbio benefits.

Specter then goes on to profile thoughtful scientists like Drew Endy, who are fully cognizant of the ethical implications of engineering life and want to engage policymakers and the public on the direction of research. This story highlights the fact that many brilliant people working on synethic biology are motivated by values—just as citizens concerned about the technology are motivated by values in forming their opinions of the work. Indeed 30 percent of respondents in the survey said that a top concern was that “it is morally wrong to create artificial life.”

So if values is a shared language, then it makes sense to tell more stories about the concrete achievements and real efforts to ensure the safety of advances in the field. In this case, talking about values in story is a lot easier than talking about values in a hypothesis.

It’s very hard for me to have a conversation about these issues, because people adopt incredibly defensive postures…The scientists on one side and civil-society organizations on the other. And, to be fair to those groups, science has often proceeded by skipping the dialogue. But some environmental groups will say, Let’s not permit any of this work to get out of a laboratory until we are sure it is all safe. And as a practical matter that is not the way science works. We can’t come back decades later with an answer. We need to develop solutions by doing them. The potential is great enough, I believe, to convince people it’s worth the risk.

That’s Drew Endy, assistant professor of bioengineering at Stanford University, talking to Michael Specter in the current issue of The New Yorker about synthetic biology. This is more than just another example of great narrative science reporting from the magazine. It’s a showcase of candid, effective, values-based discussions about the social implications of an emerging technology.

Not only is Endy’s conscientious take on the promise and peril of synbio a perfect counter to anyone who claims that scientists don’t care about ethical boundaries; he also draws attention to a conversational impasse that prevents clear thinking on how to design useful regulatory policies.

Synbio is special among other emerging technologies like neuroscience and nanotechnology in that it already promises solutions to planet-scale problems in public health and energy. Specter opens the article with the story of how Jay Keasling at UC Berkeley built a breed of E. Coli bacteria that can manufacture artemisinin, a powerful treatment for drug-resistant malaria. Researchers are also hard at work designing organisms that can churn out biofuels at industrial scales. But the same open-source genetic components that build a life-saving bug could, in the wrong hands, build terrible pathogens.

As CAP Senior Fellow Andrew Light explained in a podcast on the ethics of emerging technologies, “The attitude is not to keep synbio from happening,” but rather to create and maintain public confidence in its benefits. Hearing clear, thoughtful messages from more scientists like Endy could go a long way to supporting that goal.

As Endy tells Specter, the reason many people recoil at the power to create synthetic life is “Because it’s scary as hell…It’s the coolest platform science has ever produced, but the questions it raises are the hardest to answer.”

But if we are truly committed to evidence, we should push ourselves to take one last glance backward and review some of the biggest science policy-related lessons that 2008 had to teach. Here, then, is a Science Progress thumbnail of eight advances in science that will have long-lasting impacts on science policy—or advances in science policy that we predict will have long-lasting impacts on science. Counting down from 8 to 1, in no particular order:

8: Strong evidence that making biofuels such as ethanol from food crops is not going to save the world

Detailed global modeling by Timothy Searchinger of Princeton and colleagues showed that production of corn-based ethanol would double the amount of greenhouse gas emissions over a 30-year period instead of reducing those emissions by 20 percent, as previous calculations had suggested. Biofuels from switchgrass grown on U.S. corn lands would increase emissions by fully 50 percent, the study also found. Older research had not properly taken into account the impacts of land-use changes, such as converting carbon-sequestering rainforests to farmland. Thanks to the new understanding, many are now calling for changes in fledgling U.S. economic incentives that had aimed to boost biofuel production on domestic farms.

7: Growing evidence that we are going to have to get CO2 levels down even more than we thought if we don’t want to live in an ice-free world

Record-breaking glacial melts and improvements in climate models have led a growing number of scientists to agree that the world needs to get CO2 levels down to 350 parts per million, and avoid hitting the cap of 450 ppm that many had previously accepted as a goal. While the details are still in dispute, the need to change our behavior with regard to CO2 emissions is now beyond doubt, with real concern that even a very concerted effort at this point will barely be able to save the planet from radical mean temperature changes and greater rises in sea-level than had previously been expected. As NASA climate scientist James Hansen put it earlier this year: “Present policies, with continued construction of coal-fired power plants without CO2 capture, suggest that decision-makers do not appreciate the gravity of the situation. Continued growth of greenhouse gas emissions, for just another decade, practically eliminates the possibility of near-term return of atmospheric composition beneath the tipping level for catastrophic effects.”

6: Overwhelming evidence that in this age of global trade, the Food and Drug Administration is not anywhere near able to protect us from imported contaminants and toxins in our food, toys, drugs and other commodities

Phony heparin in blood thinners from China. Toxic melamine not just in pet food but also in baby formula. Leaded paint on toddler’s toys. Potentially dangerous phthalates such as BPA in baby bottles and intravenous tubing. E. coli in spinach. Salmonella on cantaloupes. The list goes on. It’s not that the agency is inherently inept or its employees unqualified. Quite the contrary, it is bustling with dedicated scientists and public health expertise. But short on resources, struggling with a bureaucratic structure that no longer makes sense, hobbled by a lack of needed legal authorities, the agency is today destined to fail repeatedly. Happily, the string of problems that the FDA battled in 2008 seemed at last to reach the degree of critical mass needed to get the attention of the public and Congress. Expect real action next year, both in terms of budget growth and a push for organizational reform.

5: Passage of legislation requiring “open access” publishing for all research reports resulting from work funded by the National Institutes of Health

After years of heated debate inside and outside of Congress, the NIH implemented the nation’s first open access law in April. As a result, all 80,000 or so research papers published each year that describe the results of NIH-funded studies must now be made available on a free, publicly accessible database within 12 months after publication in a journal. No longer will people who want to read the results of NIH research—paid for with their tax dollars—have to subscribe to expensive scientific journals or pay page charges to the publishers, as has long been the case. The advance will also make it easier for scientists to access each other’s work and for researchers to combine data sets from multiple published reports to perform meta-analyses—a cost-saving means of leveraging scientific data that has been difficult to implement until now.

4: The official opening of the Svalbard seed vault in Norway

This high-security, deep-freeze storage locker, nicknamed by some “the doomsday vault,” is poised to become the seed bank of last resort—the go-to place after a nuclear holocaust or other disaster. After more than a year of construction in the side of a permafrost-bound mountain, it began accepting its first deposits in 2008. The governments responsible for many of the world’s smaller, regional seed banks are not maintaining them, it turns out, or natural disasters or war have damaged or destroyed the banks. The opening of the new vault helped bring food security to the fore, reminding nations that today’s agricultural seeds are the product of ten millennia of slow, scientific work on genetic improvement, and that this legacy deserves both protection and responsible extension.

3: Congressional passage of the Genetic Information Non-discrimination Act

It took about a dozen years of lobbying by scientists, ethicists, healthcare advocates, and others, but Congress at last passed GINA, a watershed civil rights bill that prevents employers and health insurers from discriminating on the basis of individuals’ inherited genetic material. The law protects patients and genetic study participants from having their genomes used against them and, by minimizing the threat of genetic mischief, should facilitate the launch of personalized medicine, in which diagnoses and treatments will be tailored to individuals’ genetic codes. It may also boost direct-to-consumer advertising of genetic tests, some of which have proven in the past year to be of questionable medical value. Watch for an escalating debate in 2009 over how best to oversee this nascent-but-growing blend of medicine, marketing, and DNA-based narcissism.

2: The first construction on an entire bacterial genome from scratch

Scientists at the J. Craig Venter Institute in Rockville, Maryland, reported they had synthesized the complete genome of a bacterium, Mycoplasma genitalium. Previous experiments suggest that if the stitched-together DNA were inserted into a cell, it would automatically “boot up” and turn that cell into what would be the world’s first synthetic life form. Venter’s primary goal is to design, from scratch, artificial cells able to break down pollutants or produce novel biofuels. At the same time, some experts are now wringing their hands over the fact that the same technology could be used to create highly customized biological weapons. This “dual-use” aspect of synthetic biology is sure to be a major focus of scientific societies, regulators, and ethicists in 2009.

1: The appointment of a new team of scientific advisers for the next administration

What can we say? President-elect Barack Obama has created nothing less than a dream team when it comes to putting people with real scientific expertise in all the key slots that will need to make evidence-based decisions over the next four years—including his decision, released over the weekend, to post Nobel-prize-winning cancer researcher Harold Varmus and genomics whiz kid Eric Lander to the President’s Council of Advisers on Science and Technology.

The actual evidence that all these Obama-appointed scientists are going to hew to, of course, is largely dispiriting. Climate change, energy needs, food insecurity, and economic chaos—all are threatening global peace and undermining the human quest for justice. But progress is not possible without a square look at the facts. I for one am ready to swallow hard, face the unalloyed truth, and support the plans that have the best hope of getting this listing ship of state on an even keel again.

Here’s to a happy, healthy and evidence-based 2009.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

In January 2008, scientists at the J. Craig Venter Institute announced that they had created the first complete synthetic genome, setting the stage for the complete “reprogramming” of an organism with synthetic DNA. While the ramifications of this accomplishment are stunning, the news itself was not a surprise to those who have followed the progress of biotechnology research.

Technologies that can “read,” map, and manipulate the genetic code of living organisms have escalated in power and capabilities over the past 30 years, yielding an unprecedented amount of data and a more sophisticated understanding of how genetic materials give form and function to living cells. This new knowledge has, in turn, given rise to a new engineering discipline for living organisms—a discipline that has become known as “synthetic biology.”

As evidenced by the Venter Institute announcement, synthetic biology seems to be on the brink of two noteworthy accomplishments: to be able to “streamline” and redesign the genetic material of living organisms to make them operate more efficiently; and to design and assemble entirely new, artificial life forms from scratch.

How Synthetic Biology Works

According to the tenets of synthetic biology, living organisms are made up of discrete components that perform in distinctive ways, much in the same way as the functions of transistors and other electronic components can be assembled first into circuits, and then into systems designed to accomplish specific tasks. In synthetic biology, “bioengineers” are developing an inventory of biological parts, which they sometimes refer to as “biobricks,” using chemical ingredients and equipment that are common to any modern biology lab. Like electronic components, the researchers claim, these biobricks—which include genes and chromosomes, as well as proteins that can sense and report activities within a cell—can be assembled and programmed to compel organisms to operate in specific ways, or to produce custom chemicals that can later be “harvested” from cells and sold.

Both the discipline and the budding industry of synthetic biology are made possible by two concurrent technological trends. One trend is the increased power, sophistication and availability of technologies for sequencing genomes and for synthesizing and assembling DNA molecules into long strings of functional genes and genomes. The second trend is the rapidly decreasing cost of these powerful technologies. The productivity of sequencing technologies has increased 500-fold over the past 10 years, and is doubling every 24 months. At the same time, costs have declined from $1 to less than $.001 for each base pair sequenced.[1] Similarly, the productivity of DNA synthesis technologies has increased by a factor of 700 over 20 years, doubling every 12 months. The accuracy of the synthesis process has increased as well, while costs have dropped from $30 per base pair to less than $1 over the same period.[2]

These advances in automated processes and improved chemistry have made it possible to make large quantities of a wide range of moderate-length DNA sequences. The process is now so easy to do that many suppliers accept orders for custom DNA sequences over the Internet and deliver them by mail. These advances have catalyzed an industry of low-cost DNA suppliers around the globe.

Unknowns and Uncertainties

Synthetic biology represents an amalgam of scientific disciplines and sub-disciplines, public and private funding, public and private institutions, complex cross-sector collaborations and, in some cases, new approaches to intellectual property protection. Not surprisingly, most of the significant synthetic biology research and development is taking place in the United States, where most of the world’s biotechnology R&D activities are also centered. But other countries, most notably those in Europe, are also investing heavily in synthetic biology development.

Proponents of this new engineering discipline claim that the ability to create, manipulate and cheaply manufacture customized or unique life forms will produce many benefits across a wide range of applications, from medicine to energy generation and environmental remediation. In the near term, their vision of the future includes designer microorganisms and other engineered life forms that can be deployed as “devices” to stimulate tissue repair and cell regeneration and sense changes in body chemistry that might be precursors to disease. They also say synthetic organisms will be able to produce new kinds of pharmaceutical compounds and plastics, as well as detect toxins, break down air and water pollutants, destroy cancer cells, and generate hydrogen and other substances for new energy technologies.

But that vision does not adequately acknowledge an equally lengthy list of potential risks, as well as broad scientific and social concerns, that as yet are largely unaddressed.

The most obvious risk, which has caused the most concern to date, is the ability bestowed by synthetic biology to design and manufacture biological weapons in the form of virulent pathogens, most notably microbes such as bacteria and viruses. Other risks come under the heading of “bioerror,” rather than bioterror: namely, the consequences of accidental release of engineered organisms that were not intended to come into contact with the open environment; the mutation of “harmless” man-made organisms into ones that are harmful to people and/or the environment; or the effects of alien organisms that invade and destroy native populations and become impossible to eliminate, in much the same way as non-native, “invasive” species of plants, animals and microbes do today.

Many other critical questions have to do with broader, unacknowledged issues about scientific uncertainty. In 2007, a global consortium organized by the U.S. National Human Genome Research Institute, or NHGRI, published the results of a four-year study to identify and analyze the functional elements of the human genome—the “biobricks” upon which the discipline and industry of synthetic biology (and the entire biotechnology industry, for that matter) are built.[3] To the researchers’ surprise, according to the NHGRI announcement, they found that the genome is not a “tidy collection of independent genes.” Instead, it appears to operate as a “complex, interwoven network,” where components interact and overlap with one another and with other components in ways that are not yet fully understood.

The study, called the Encyclopedia of DNA Elements, or ENCODE, raises serious questions for synthetic biologists about the limitations of the “engineering” paradigm that they are applying to living systems. While there may be encyclopedic knowledge of the mechanics of electronic components and their interactions, clearly there remain far more questions than answers about the biological mechanisms that govern living organisms.

In fact, in many respects scientists know less today about these mechanisms than they did even just five years ago. As the NHGRI said at the release of the ENCODE report, scientists are now challenged “to rethink some long-held views” about genetic components and what they do. Given this scarcity of knowledge, can synthetic biologists truly claim to know enough about living, reproducing biological systems to design artificial organisms—and, more important, to reliably predict their behavior and effects once they have been released? Are the parallels they draw between electronic components and biological parts accurate, or even relevant?

More specifically, synthetic biologists have left unaddressed several critical mechanisms that limit their ability to predict the long-term consequences of synthetic organisms. One is the effects of horizontal gene transfer—the natural mechanism that moves genetic material between species and even kingdoms and facilitates, for example, the transmission of avian influenza to other animals, including mammals—when artificial genes make their inexorable move across species to indigenous organisms, or vice versa. Also unaddressed are issues about mutation and evolution; that is, how synthetic organisms will adapt to their environment once they are released. Likewise, synthetic biologists do not know how effective are the methods (such as sterilization of engineered organisms) that they say they will use to prevent synthetic life forms from reproducing. In fact, a 2004 National Academies study addressing the “bioconfinement” of genetically engineered organisms stated flatly that no single method could be considered effective.[4]

Under normal circumstances, these kinds of issues might best be considered as part of a scientific research agenda, and not as topics that should fall within the purview of governance and regulatory oversight. But the circumstances surrounding synthetic biology’s development are anything but normal. Rarely, if ever, has scientific discovery been so tightly coupled with proprietary commercial development, with so little time set aside for reflection and testing, so little consideration of results in the context of broader understanding, and so little independent review of research findings in anticipation of commercial release.

In fact, the technologies and products for creating synthetic components are already affordable and widely available to virtually anyone with access to the Internet, a credit card and a shipping address—or to any clever biology student, for that matter. When Eckard Wimmer, professor at the State University of New York, Stony Brook, who first synthesized the poliovirus from single nucleotides, was interviewed for a 2006 journal article on synthetic biology, he said, “With this technology you can make poliovirus for 50 cents. [I]n five years you [could] have this synthesis facility in every university lab. … You cannot stop this technology because there is a great hunger for it from many biologists.”[5]

Wimmer’s “five years” could conceivably come much sooner. For two years before the Venter Institute’s January 2008 announcement, for example, hundreds of undergraduates from around the world had spent their summer holidays making biological parts and building systems with them. In 2006 alone, 32 teams that participated in the International Genetically Engineered Machines, or iGEM, competition, hosted by the Massachusetts Institute of Technology, added 724 new biobricks to MIT’s Registry of Standard Biological Parts. In 2008, 84 teams and more than 1,000 undergraduate participants from 21 countries across Asia, Europe, Latin America, and the U.S. participated. Biotech companies and venture funds from around the world sponsor teams in the competition.

The iGEM competition is only one example of the investment money and taxpayer-funded research dollars that are flooding the nascent field of synthetic biology. The potential payoff for the ability to build and sell novel living organisms is considered to be so great that venture capitalists, government agencies and multinational corporations, including BP (formerly British Petroleum), Shell, Cargill, and Dupont, are already investing in research and partnerships with startup companies to drive synthetic biology products to market as quickly as possible.

Synthetic biology products may eventually comprise a significant portion of what analysts at Morgan Stanley estimate will be a trillion-dollar market for alternative fuels by 2030. Several companies, including Dupont, already produce commercial “bioplastics” that are manufactured by semi-synthetic bacteria. The synthetic biology company Solazyme recently announced that it would partner with Chevron, the world’s seventh-largest corporation, to develop biodiesel from synthetically redesigned algae. BP is an equity investor in Craig Venter’s company, Synthetic Genomics, Inc. (Financial terms for the latter two deals were not disclosed by the companies.)

In addition, several U.S. government agencies, including the Departments of Defense and Energy, the National Institutes of Health, and the National Science Foundation, have already made investments of millions of dollars in synthetic biology centers and projects, and published NSF research priorities for the 2009 fiscal year indicate synthetic biology funding may increase.[6] A handful of science-minded foundations, most notably the Bill and Melinda Gates Foundation, are investing in synthetic biology projects. Not wanting to be left behind, the European Union is funding the development of a European strategy for synthetic biology, including “stimulation activities” for the mobilization of public and private resources to fuel the nascent industry. Researchers in Africa, Canada, India, Israel, Japan, Korea, Latin America, Slovenia, Turkey, and many other countries are said to be actively pursuing synthetic biology projects as well.

A Profound Challenge for Governance

Synthetic biology poses what may be the most profound challenge to government oversight of technology in human history, carrying with it significant economic, legal, security and ethical implications that extend far beyond the safety and capabilities of the technologies themselves. Yet by dint of economic imperative, as well as the sheer volume of scientific and commercial activity underway around the world, it is already functionally unstoppable. With hundreds of millions of dollars worldwide already spent or committed to synthetic biology R&D across several sectors, and what is almost certainly millions more in undisclosed venture financing and corporate partnerships, companies are driving hard to deliver products for commercial release. This drive to market, coupled with no substantive expert, stakeholder or public policy discussion regarding the balance of risk and benefit for its products, has led many observers to declare that synthetic biology is a juggernaut already beyond the reach of governance.

Proponents are quick to point out that synthetic biology research and its products are not entirely unregulated. In the United States, the NIH still requires laboratories receiving NIH funds to comply with laboratory procedures as outlined in their Recombinant DNA Guidelines. A drug produced by a synthetic organism would be evaluated like any other by the Food and Drug Administration. Also, depending on the application, the Environmental Protection Agency or the U.S. Department of Agriculture would oversee the potential release of synthetic organisms into the environment.

This argument, however, presumes that present regulations are appropriate for evaluating the products of synthetic biology. The critical question that has not been explored is whether synthetic biology poses unique risks that are unconsidered by present health and safety regulations (and regulatory approaches), as well as by financial regulations that govern intellectual property rights and trade.[7]

Some of synthetic biology’s researchers, investors and funders acknowledge the possibility of unintended consequences, but for the most part they minimize the risk, openly acknowledging that they want to avoid synthetic biology becoming the new target for the negative perceptions that many people around the world continue to hold for biotech crops and other biotech products. As a group, they overwhelmingly insist that if synthetic biology is to fulfill its promise, scientists must be trusted to do the right thing, and that existing regulations are sufficient to shield the public from any hazards that might result from the products of synthetic biology. This perspective is best expressed by a recent statement made by Victor de Lorenzo, vice director of the National Centre of Biotechnology in Madrid, Spain. In a 2006 article in the journal of the European Molecular Biology Organization, he said, “I think the question of regulation should not be the first question. … Let’s first see what [the technology] is good for. If you first ask the question about risk, then you kill the whole field.”[8]

The main argument used in favor of self-regulation of synthetic biology’s processes is that they are simply the result of a more sophisticated application of the aforementioned laboratory techniques developed for working with recombinant DNA. As for the products of synthetic biology, practitioners argue that they already fall within the purview of existing regulations that govern genetically engineered organisms and the substances that these organisms may produce. But these characterizations sell short several fundamental, related differences between the two practices, and ignore the history of how genetically engineered organisms came to be as lightly regulated as they are today.

The Difference Between Synthetic Biology and Genetic Engineering

These differences and regulatory history are worth reviewing before turning our attention to recommendations for improving the governance of synthetic biology’s products and processes.

1. Synthetic biology is based on the intentional design of artificial biological systems, rather than on an understanding of natural biology.

Like traditional genetic engineering, synthetic biology uses recombinant DNA techniques to manipulate and construct various kinds of DNA molecules. The goal of a synthetic biology engineering project, like that of traditional genetic engineering, is to create an organism that does what its engineer has designed it to do. But as one report notes, “genetic engineering [is] a cut and paste affair,” shuttling traits from one naturally existing organism to another. “By contrast,” the report continues, “today’s synthetic biologists are armed with the biological equivalent of word processors.”[9] That is, rather than simply being able to splice DNA “words” into or out of existing organisms, synthetic biologists are now in the early stages of learning to write and assemble from scratch the entire paragraphs of code needed to make an entire organism.

Creating unprecedented life forms that can grow, reproduce, mutate, evolve and transfer their genes to other, naturally occurring organisms will yield consequences that are impossible to anticipate with today’s knowledge. The process is dramatically different from modifying the function of an existing organism using the techniques of traditional genetic engineering.

For example, part of the early sales pitch for genetic engineering was that it is more precise and predictable than traditional cross-breeding. But in reality, genetic engineering often triggers unpredictable mutations in an organism’s genome. While most of these mutations are screened out of commercial transgenic products before they reach the market, they do occur. And when they do, they can cause unexpected and sometimes harmful changes in a living organism. (Witness the foreshortened life span and health problems that have plagued genetically engineered and cloned animals.)

While synthetic biologists use the tools of traditional genetic engineering, they aim to eliminate such random events by designing, writing, or rewriting an organism’s genetic code, then synthesizing the sequence of molecules themselves, using the aforementioned “standardized” parts and DNA synthesis equipment. They say such stripped-down, intentional design, coupled with directly synthesizing the genome themselves, will eliminate much of the expensive trial and error that typifies traditional genetic engineering. They believe that they will be able to far more quickly and cheaply fabricate new or more “efficient” life forms of their own design that predictably and precisely display the desired traits.

But as mentioned earlier, there remain many unanswered questions about synthetic biology that bear only a partial resemblance to those asked about traditional genetic engineering. Among them is what effects artificial life forms may have on natural organisms, and vice versa. The larger, more important point is the presupposition by synthetic biologists that their existing understanding about DNA and the processes of heredity is sufficient to enable them to safely and predictably eliminate what they believe to be “inefficiencies” in natural organisms.

As evidenced by the ENCODE study, this is not specious questioning by fearful people who do not understand the science. To wit: researchers are only now beginning to discover that the so-called junk DNA that is present in all organisms (it comprises between 80 and 90 percent of the human genome, for example) serves a critical function in organisms, even though it does not contain instructions for making proteins or other cell products. What is the meaning of “efficiency” when researchers understand only a fraction of how basic biological systems function and how organisms interact with each other and their environments? What is the long-term effect of willful action in the context of so much scientific ignorance and uncertainty?

Finally, the fact that synthetic biology technology can be used to design and synthesize dangerous pathogens not found in nature also challenges existing laws regarding what are known as “select agents”—the toxins and pathogens that can pose a severe threat to human, plant or animal health that are regulated by the Centers for Disease Control and Prevention. Traditional recombinant DNA technology has raised similar or related concerns, but the de novo products that synthetic biology promises will eliminate the need for those with ill intent to gain access to known, naturally occurring agents or naturally occurring genetic material from these agents. This not only greatly expands the potential availability of select agents but also circumvents the CDC regulatory framework that presently governs their possession and use.[10]

2. Synthetic biology’s practitioners are not, as a rule, biologists or even molecular biologists. Many are computer scientists or come from disciplines that do not study or work with whole organisms, but instead apply an even more mechanistic, reductionist perspective to living systems than do traditional genetic engineers.

Synthetic biology’s design and construction of simplified biological systems are, at the very least, supposed to provide scientists with a useful way to test their understanding of the complex functional networks that mediate life processes. However, this understanding is still extremely limited, and extends only to the cell and to a few very small, very simple organisms. As a rule, synthetic biologists do not concern themselves with the relationship between the genetics of organisms and their environment; that is, with how whole organisms mutate and evolve, or how disparate species exchange genetic material in nature, outside of the laboratory.

Traditional genetic engineers generally hold this reductionist perspective as well, but even if they tend to ignore the long-term evolutionary or network effects of their creations, at least they have had to learn how to make alien DNA behave properly within the genomes of natural plants and animals. Synthetic biologists, having no such restrictions, can ignore even this relatively low level of complexity.

But at whose peril? If the goal is a regulatory environment that intelligently anticipates the unintended consequences of a new technology, these distinctions and relationships—between molecules, cells, organisms, and ecosystems—are critical. Biologists who study organisms and ecosystems are steeped in the complexity of biological systems, and understand the limitations of their knowledge about how organisms behave and interact in the real world. The plants, animals, and microbes they study demonstrate to them on a daily basis that the cell and its molecular components are not, in fact, wholly analogous to electronic circuitry. DNA and other components of heredity do not always behave in nature in the same way as they do under the controlled laboratory conditions of synthetic, or even traditional molecular biology. Without this understanding, synthetic biologists cannot reliably predict how their inventions will behave in the natural world.

3. If the goal for synthetic biologists is both public acceptance and credible risk assessment of their products and processes, genetic engineering should not be considered a model for best practices in the context of proper governance and regulation of biological innovations.

A thorough examination of the historical record shows that politics and industrial interests, at least as much as scientific evidence, drove the regulatory process for genetically engineered products from its genesis in the White House Office of Science and Technology Policy in 1986. The same is true today of synthetic biology.

OSTP’s starting assumption for biotech regulation, made at the behest of industry, was that only the products of genetic engineering, and not the radical new process (recombinant DNA) that was used to create them, should be considered in a safety evaluation. This assumption was noted as scientifically questionable by several administrators and scientists inside the FDA itself at the time the first regulation for a genetically engineered organism was being developed. Among other things, they noted, the product category was brand-new, thus literally no evidence or historical data, other than that provided by industry applicants, existed upon which to base such a statement. What’s more, they said, while various experts in molecular biology, chemistry, toxicology, and related fields were asked to provide input to the FDA regarding risk, not one risk analyst was invited to do so—despite the fact that the entire purpose of risk analysis is to scientifically assess the potential effects of taking action in the presence of uncertainty. By selectively narrowing the scope of their concerns and a priori not considering the process of genetic engineering itself as part of their risk evaluations, regulators were able to speed the products of genetic engineering to market.[11]

When confronted with the historical record on biotech regulation, proponents often say that there have been no known health or environmental effects as a result of genetically engineered organisms, so the approach was the right one. However, in the United States at least, there is no objective way of knowing whether that statement is true. Existing regulations contain no requirements for monitoring the movement of genetically engineered organisms in the field once they have been approved, or for labeling products with genetically engineered ingredients in the marketplace. There is no tracking or monitoring of the potential effects that engineered organisms may be producing in other living things. As a result, both the organisms and their effects are literally untraceable, should a health or safety issue arise.

Nonetheless, synthetic biologists today are arguing that existing laws and policies are sufficient for their products in the presence of even more scientific uncertainty and less historical data than are available for transgenic organisms. It is an easy argument to make, and one that is not likely to be refuted by the regulators themselves, since both U.S. law and regulatory philosophy tends to place the burden of proof regarding risk or hazard on those who oppose a new technology. If new regulations cannot be avoided, agencies often work closely with regulated industries to develop the rules and select the methods that will inform the assessment process. As a result, safety determinations about a technological innovation are almost always based on evidence that regulators know the scientists can provide—a situation that inevitably leaves unasked many of the larger, more complex questions about potential hazards that scientists cannot easily answer.

Self-regulation is already running into snags in the context of intellectual property; that is, who owns and controls the discoveries upon which the nascent industry of synthetic biology is based.

Many academic scientists who are at the forefront of developing the technology publicly support the development of a synthetic biology “commons”—a legal framework for public access to common resources and goods (such as water) for a given community. In the context of synthetic biology, an intellectual property commons would ensure that standard biological parts remain freely available and unfettered by patent thickets that have been known to slow or halt academic research, stifle innovation and keep the fruits of discovery out of economic reach for those who might need them most. At the same time they are encouraging the development of this bioparts “commons,” and in seemingly contradictory fashion, many of these same academics serve on the scientific advisory boards of synthetic biology companies that are working to develop the proprietary patent portfolios that are required to attract investors.

This paradox spotlights another critical issue regarding the credibility and objectivity of the evidence that scientists provide regulators regarding the risks of synthetic biology’s products and processes. Most synthetic biology researchers, even more than traditional biotechnologists, operate simultaneously in several spheres: as academic researchers receiving government funding for research and product development, as inventors seeking patentable discoveries, as company founders receiving investment capital from the private sector to finance product development based on those patents, and as members of scientific advisory boards for groups that are engaged in similar activities.

How these conflicts affect synthetic biologists’ attitudes and perspectives on risk, and their impact on both the quality of research and the long-term viability of the nascent synthetic biology industry, has not been addressed in proponents’ reports or studies on the topic.

Recommendations for Improved Governance (listed in terms of priority)

The wide variety of products, activities and players involved in synthetic biology research and development can be separated into some general categories (see Appendix). Hundreds of scientists, companies and organizations worldwide are associated with these categories.[12] Not all of them are key to emerging governance issues, but it is important to keep all of them in mind, because many of these categories include product offerings, methods, and practices that are shared with traditional biotechnology research and product development (such as DNA synthesis).

As a result, a very large “industry-in-waiting,” so to speak, is poised to take advantage of advancements in synthetic biology. Without regulatory acknowledgment of the differences between traditional genetic engineering and synthetic biology products, these players will not have to change their existing practices or offerings very much to “upgrade” into the synthetic biology category. This will quietly increase the sector’s activity, the potential volume of products and, subsequently, the risks it poses. It is also important to note that some categories of research and development in synthetic biology are closely related to nanotechnology, another area of scientific innovation that has proven to be challenging for proper regulatory oversight and governance.

Because of the untested nature of both the risks and the benefits of synthetic biology, and the tremendous financial impetus to bring commercial products based on the technology to market, it is important to take action as quickly as possible to improve the oversight and governance of synthetic biology. Four recommendations are given below. The goal is to get to Priority 3, the comprehensive risk assessment, as quickly as possible. Priorities 1 and 2 must be done first in order to best inform that assessment, and they, too, should be done without delay.

Priority 1. Research and report the current regulatory situation for synthetic biology across agencies and sectors. Because of the “déjà vu” argument being presented by proponents, this research should include a reassessment of the viability and utility of regulations for the products of traditional genetic engineering.

A detailed and comprehensive assessment of the regulatory environment for synthetic biology, both in the United States and abroad, is critical in order to provide a realistic foundation for future conversations about this technology. Because synthetic biologists are likely to use the official safety record of genetically engineered organisms as an argument for no additional regulations, it is important to reassess the shortcomings of these existing policies as well.

In addition to including the process as well as the products of synthetic biology, this assessment must include the current thinking about scientific uncertainties in genomics-related disciplines, starting with the ramifications of findings such as those produced by the ENCODE study.

In the context of the synthetic biology “commons” and other intellectual property issues, the assessment must also consider how synthetic biology is being considered within the World Trade Organization and in the context of its Trade-Related Aspects of Intellectual Property Rights agreement (commonly referred to as TRIPS), as well as within individual countries’ thinking and activities in the area.

A tremendous amount of synthetic biology activity, much of which is intended to eventually yield commercial products, is taking place around the world. It is critical to learn which way governments around the world are leaning in terms of synthetic biology regulation. If one of their scientists or companies were to announce that it was ready to ship a commercial synthetic organism in the next 12 months, what would be the policy response, if any?

Also critical to this assessment will be mapping where various agencies’ responsibilities and practices create gaps, conflicts or overlaps in regulatory coverage. For example, given our assessment that there are fundamental differences between synthetic biology and genetic engineering, under what circumstances will (and/or should) existing biosecurity regulations be applied?

As a starting point, it might be helpful to use the concept of “select agents” and the recent report from the National Science Advisory Board for Biosecurity on synthetic biology.[13] Select agents are pathogens or biological toxins that have been declared by the Department of Health and Human Services or by the USDA to have the “potential to pose a severe threat to public health and safety.” Possibly the most influential agency in the context of synthetic biology regulation, NSABB represents more than a dozen U.S. government offices and agencies, including EPA and USDA, which may be charged with regulating the products of synthetic biology.

In the summary of its findings, the report noted the need for additional clarity about existing regulations, because “responsible agencies, affected scientists, and commercial providers differ in their interpretation of the laws, regulation and policies” as they affect synthetic biology. Given the global ubiquity of synthetic biology research and the possibly imminent release of synthetic biology products, policymakers need to be able to gauge the effectiveness of the existing oversight system—including the consistency of coordination (or lack thereof) across agencies sharing the oversight responsibility and the realities of field practice.

Furthermore, the report stated that the speed of technological advances “will require governance options that are capable of keeping pace with rapidly evolving science.” One of the questions to be addressed, the answer to which would be of broad utility, is “How can possible risks associated with the generation of novel organisms be addressed?”

It might also be useful to investigate whether non-obvious policy alternatives exist that could be deployed if agencies cannot be compelled to take proper action.

Priority 2. Conduct a comprehensive critique of the synthetic biology reports that have been published so far, and assess their impact on decision makers.

Virtually all the reports on synthetic biology have come from the synthetic biology community or from a proponent’s or an opponent’s point of view. These reports have serious logical flaws and omissions of fact and critical perspective, and they should be countered by a more objective source as soon as possible.

Of the most concern in the context of risk and governance are the reports that uncritically support synthetic biology, as they encourage development and commercial release with little or no acknowledgment of the degree of scientific uncertainty that surrounds the endeavor. A 174-page report on synthetic biology published by Bio-Economic Research Associates in 2007 and funded by the Department of Energy (which itself has invested heavily in synthetic biology research), contained but a single, three-quarter-page discussion of the limitations of the engineering paradigm as applied to living systems. Giving such short shrift to a topic that is still under deep consideration in the broader scientific community lends an air of certainty to a highly uncertain endeavor. Such under-representation has real significance from the perspective of investment and economic risk, as well as from that of health and the environment.

Similarly, and perhaps most disappointingly, a $500,000 report funded by the Alfred P. Sloan Foundation on synthetic biology’s “Options for Governance” was co-authored by two of the pioneering institutions of synthetic biology, the J. Craig Venter Institute and MIT, along with the Center for Strategic and International Studies.[14] Promoted as a “stakeholder” study on the broader societal risks and implications of synthetic biology, the Sloan study instead focused mainly on the largely benign laboratory procedures for handling synthetic organisms in the context of biosafety. It did not substantively address the more significant issues of scientific uncertainties, intellectual property conflicts, or the social implications and the intended and unintended effects of synthetic biology’s products on human health or the natural environment. Not surprisingly, given its co-authors, the “options for governance” that were presented in the study’s conclusions weighed heavily in favor of self-regulation.

Discovering the degree to which such biased perspectives and recommendations have affected decision makers will be an important step in a more relevant and comprehensive approach to assessing synthetic biology’s risks. This knowledge will also be an important factor in deciding how quickly action must be taken to counter their biases, as legal judgments or official decisions on synthetic biology become imminent.

Priority 3. Using (and challenging the assumptions of) the data and scenarios in the above-mentioned reports, conduct a comprehensive risk characterization of synthetic biology.

Given the financial and intellectual momentum of the nascent industry, it is not surprising that there is a tremendous aversion in the synthetic biology community to speaking directly about the risks of unintended or unanticipated consequences, or to involving risk practitioners who are schooled in methods that are designed for highly uncertain issues or experts from other sectors in assessments of its future. It is very difficult to find a synthetic biology report that uses the word risk more than in passing, let alone directly addresses the subject at any depth.

One reason for this omission is that many scientists believe the word risk refers to a technical calculation of probability that is demonstrable only by way of “evidence” that a risk exists. Such calculations are near impossible, however, when analyzing technological innovations, where there are no historical precedents other than by analogy and sparse data to use in a probability calculation. Yet without data, these scientists say, there is no risk, only speculation. While technically “scientific” in its approach, this circular argument forces decision makers to consider only a very narrow, pre-determined and ultimately subjective view of the important issues they are being asked to address.

However, there is another approach to risk assessment that has proven very useful for decisions regarding scientific and technological innovations. This approach combines data analysis and extensive deliberation with a broader representation of relevant scientific expertise, as well as parties who are interested in the issue or who will be affected by the outcome of the analysis. This process of analysis and deliberation is described in the 1996 National Academy of Sciences study, Understanding Risk: Informing Decisions in a Democratic Society.[15]

Should this type of assessment be undertaken, the analytic deliberative approach could be augmented with a methodology that is under development by myself and Baruch Fischhoff at Carnegie Mellon University, designed to address unprecedented risks such as those presented by synthetic biology. It uses scenario narratives to develop comprehensive risk models that are computable over time, as research continues and data become available.[16] There are several credible scenarios available regarding synthetic biology that, taken together, could provide the foundation for characterizing and assessing synthetic biology’s risks and benefits.

Such an assessment would be designed to yield five important outcomes:

(a) A mutually agreed-upon risk/benefit model for lawmakers to use in regulatory decisions. This model would map critical scientific uncertainties associated with commercialization and/or release of synthetic organisms (e.g., the effects of evolution, environmental and health effects, assessment of product versus process, the significance of horizontal gene transfer, synergies between synthetic biology and nanotech), as well as economic, legal, biosecurity, social and ethical implications for the United States and its relationship to other countries;

(b) An understanding of the degree to which existing biotech regulations can usefully be applied to synthetic biology processes and products and, conversely, where they should not be used;

(c) A scientific research agenda for addressing knowledge gaps and known risks as revealed by the assessment process;

(d) A contingency/preparedness plan for unintended consequences, including potential legal strategies should rational approaches not prevail; and

(e) A public database/repository to collect information on synthetic biology so that risks (and regulations) can be reassessed as new data are added and uncertainties are reduced.

Priority 4. Convene cross-sector stakeholder working groups on elements in the assessment that were deemed most important to address.

After the risk characterization has been completed, stakeholder groups should develop policy recommendations for addressing the issues and elements of concern. At this point, these groups would likely be organized around at least the following three elements:

(a) Scientific uncertainties. How should the nature and extent of the scientific uncertainties in synthetic biology, discovered during the risk-characterization process, affect regulatory policies? Are there examples of more iterative (Bayesian) approaches to policy that can be deployed for issues such as these, where well-informed decision makers have determined there is a need to move forward with research and development despite scientific uncertainty? What is required in terms of research funding to better address these uncertainties in advance of commercial deployment?

(b) Patents and intellectual property. How do existing patent and intellectual property laws add to or lessen the broad risk profile for synthetic biology products? What would happen if a significant portion of the field’s intellectual property remained in the public domain or commons, as some synthetic biologists want? What would be the social and economic implications of various patent approaches to synthetic parts and organisms? Having this conversation soon, before too many synthetic biology patents are issued, could be tremendously useful.

(c) Human factors. What human factors affect the regulatory/policy profile for synthetic biology’s products and processes, and what kinds of interventions can best address them? Who are the equivalents of the nuclear plant operators in synthetic biology scenarios, i.e., what constitutes risky behavior for humans using synthetic biology in the field? This group would look at implications for deliberate misuse of the technology as well as for bioerror.

Conclusion: Opportunity Costs

If even a fraction of its proposed applications pan out over the long term, synthetic biology has the capacity to radically change our approach to some of the most pernicious problems of our time. That human beings may someday know enough to safely and predictably engineer life forms that can eliminate ocean pollution, generate sustainable energy sources, or help to eliminate infectious diseases will be nothing short of transformative. So it is no wonder, standing at what seems to be the very brink of such tremendous promise, that proponents of synthetic biology want to dismiss most conversations about risk as speculation.

But it is important to note that in its early stages, the promised benefits of any technological innovation are purely speculative as well. While there may not be historical precedent for synthetic biology, the history of science is replete with examples of the high price of biological interventions that were brought to market or released without sufficient consideration of consequences.

For example, the toads that were imported from Hawaii to rid Australia’s sugarcane plantations of beetles have instead eaten all the native amphibian and invertebrate species in their path—except the cane beetle. The morning-sickness drug DES, sold to millions of women between 1940 and 1971, was almost entirely ineffectual for its ostensible purpose, yet has passed along its carcinogenic mutations to children in every subsequent generation. The overuse of man-made antibiotics has created new strains of “superbugs” that are virtually unkillable and can make being admitted to a hospital more life-threatening than staying at home. And we have not yet begun to tally the costs of regulatory myopia about nanotechnology, where agencies remain loathe to step in despite the demonstrated health and environmental risks of some nanomaterials.

Synthetic biology stands to have a far greater impact than all of these—especially if its products are allowed to be released without pausing for thoughtful consideration of risk and benefit in the context of scientific uncertainty. Many of synthetic biology’s proponents see such consideration as an opportunity cost, maintaining that both money and benefit are lost each day their activities are questioned or delayed. But the role of government is to understand these developments in a broader context, properly oversee them, and ensure that society is not forced to bear the cost of that opportunity, should plans go awry. Today, with the benefit of hindsight, we have developed the methods to practice foresight in these matters. We have in hand the means to practically address scientific uncertainty and risk for the benefit of all stakeholders: the industry, the independent research community, and the public. The sooner and more willingly that we as a society embrace those means, the greater the opportunity will be for synthetic biology to fulfill its promise.

I am grateful to David Rejeski at the Woodrow Wilson International Center for Scholars for supporting the research and the writing of this report; and to the Center for American Progress and Rick Weiss for its final production and publication. All views expressed herein are my own, and do not necessarily reflect the positions of either organization.

Denise Caruso is executive director and co-founder of the Hybrid Vigor Institute, an independent, not-for-profit research organization and consultancy that is dedicated to interdisciplinary and collaborative problem solving. She is the author of Intervention: Confronting the Real Risks of Genetic Engineering and Life on a Biotech Planet, which won a Silver Medal in the Science Category of the 2007 Independent Publisher Book Awards, and was listed as a “Best Business Book of 2007” by strategy+business magazine. She also edits and contributes to the Institute’s blog, at hybridvigor.org and, in 2008, was named a contributing editor for strategy+business, where she writes about risk, public policy, and innovation.

Caruso has developed and served as co-principal investigator on research projects that aim to improve upon traditional methods of risk and decision analysis for innovations in science and technology. Topics of case studies in which she has been involved, funded by the National Science Foundation, have included the risks of xenotransplantation using genetically modified pigs, and the risks of pandemic avian influenza. She is an affiliated researcher at the Center for Risk Perception and Communication at Carnegie Mellon University. Since 2003, she has been a member of Global Business Network, a worldwide organization that works to enhance competitive and adaptive capacities in organizations through collaboration, scenario development, and strategic planning.

Caruso is also a veteran journalist and analyst. In 2007, she wrote “Re:framing,” a column on innovation and creativity, for the Bright Ideas page in the Sunday Business section of The New York Times. She also chronicled the converging industries of digital technology and interactive media from the mid-1980s to 2000. For the five years prior to founding Hybrid Vigor in 2000, she wrote the Technology column for the Monday Information Industries section of The New York Times.

One of the first journalists to focus on the intersection of technology, commerce, and culture, Caruso is a director emerita of the Electronic Frontier Foundation. She was elected to the board of directors of the Independent Media Institute in January 1995, and continues to serve in that capacity. She is a trustee of the Molecular Sciences Institute, a non-profit laboratory conducting research into basic biological processes. She also serves on the advisory boards of several organizations, including Public Knowledge and London-based SustainAbility.com; she recently became an advisor to Echo & Shadow, an intelligent robot company.

Appendix: An Overview of the Synthetic Biology Landscape

Hundreds of scientists, companies, and organizations are already engaged in synthetic biology research and development. A comprehensive, albeit somewhat dated list, with an emphasis on research and researchers in North America and Europe, may be found in the European Union report “Synbiology: An Analysis of Synthetic Biology Research in Europe and North America,” published in October 2005.[17]

The general categories of key products, applications and players in the field of synthetic biology (listed alphabetically) are populated as follows.

• Funders and investors, including venture capital firms, U.S. government agencies and foundations, and corporations directly funding scientific research and/or development;
• Government agencies and regulators, including those governing trade and commerce as well as those responsible for risk regulation;
• Issues analysis and strategy, which includes media coverage; private and public studies and reports on the economic, ethical, and political impact of synthetic biology, including intellectual property protection; and risk analysis and decision-making/regulatory strategies by industry organizations, consulting firms, non-government organizations, and academic researchers;
• Laboratory-based molecular and nanotechnology development, which includes the development of molecular machines and strategies for machine evolution and the development of self-assembling biomaterials and bioelectronics, reporters, and sensors and artificial life;
• Products and applications of synthetic biology, including artificial genes and genomes; drugs, chemical agents, plastics, fuel, electricity, and other products manufactured by synthetic or semi-synthetic bacteria; tissues, organs and organisms generated by design; and biofuels and bioelectricity;
• (Practical) engineering in living organisms, which includes engineering of structural functions; artificial evolution and strategies for optimizing artificial evolution; design of semi-synthetic organisms; engineering of cell regulatory functions; the biobricks strategy of biological parts characterization, fabrication and assembly; and engineering of programmable systems of organisms;
• Related and enabling technologies, which include DNA sequencing, synthesis and design equipment; analytic devices such as diagnostics, microarrays, chromatography, and microfluidic chips; and cell technology, including cell cultures and stem cell technologies; and
• (Theoretical) computerized modeling, which includes computer analysis and modeling of natural systems, molecular networks, and synthetic biology systems.

Within these categories, the activities of a handful of key players are being closely watched. These are some of the best known:

1. George Church: professor of genetics, Harvard Medical School; director, Center for Computational Genetics, Harvard University; co-founder, Codon Devices; co-founder, LS9 Inc.

Considered one of the pre-eminent synthetic biology researchers, Church is also a well-known figure in the larger biology community. His 1984 Ph.D. dissertation included a description of the first direct genomic sequencing. He also co-initiated the Human Genome Project while serving as a postdoctoral fellow at Biogen and as a Monsanto fellow at the University of California, San Francisco. As director of the Center for Computational Genetics, he is developing broadly distributed, integrated models for biomedical, biofuel, and ecological systems. The Center’s research currently focuses on genome engineering and synthetic biology development to build “genetic circuits,” vaccines and optimal drug biosyntheses. Among many other active and advisory affiliations, Church also co-founded Codon Devices in Cambridge, the first venture-backed synthetic biology company that is focused on synthesizing very long pieces of custom DNA, and LS9, which is designing biofuels produced by microbes created via industrial synthetic biology.

2. Drew Endy: assistant professor in the Department of Bioengineering at Stanford University

The former assistant professor at the Massachusetts Institute of Technology moved to Stanford University in fall 2008 to become its first synthetic biology professor and is probably the best-known and most public face of synthetic biology. Widely acknowledged as a founder of the field, he is one of its most active participants in all aspects, from academic research to social implications and commercial development. At MIT, he co-founded the Registry of Standard Biological Parts as well as the annual iGEM international synthetic biology design competition, where teams of undergraduate students create novel biological parts and build them into working systems. He is a co-founder of Codon Devices.

He also started the non-profit BioBricks Foundation, whose mission is to ensure that standard biological parts remain freely available to the public and to encourage the development of codes of standard practice for the use of standard biological parts.

3. Foundations

a. The Bill & Melinda Gates Foundation

The Gates Foundation is helping drive synthetic biology research out of the lab and into applications by investing in health-related synthetic biology products. In addition to the $42.6 million it granted to three organizations for the development of a synthetic microbe to produce an anti-malarial compound, the Foundation has granted $19.4 million to a consortium, led by the Seattle Biomedical Research Institute’s Viral Vaccines Program, to create synthetic molecules to trigger antibodies against HIV.[18]

b. The Alfred P. Sloan Foundation

The Sloan Foundation is one of the few remaining private philanthropies that funds direct research in selected areas of scientific significance. In 2005, Sloan’s Bioterrorism Program awarded $500,000 to the J. Craig Venter Institute, in collaboration with the Center for Security and International Studies and the Synthetic Biology Group at MIT, to examine the risks and benefits of synthetic genomics in the context of regulations and governance.

Through its Bioterrorism Program, Sloan has also made several other grants aimed at addressing issues of potentially dangerous applications of synthetic biology. These include a feasibility study to develop a global network of bioscientists, support for a workshop on Genomics for Development, Bioterrorism, and Human Security, and an assessment of the World Health Organization’s oversight of smallpox virus research.

4. Jay Keasling: director, SynBERC, University of California, Berkeley; co-founder, Amyris Biotechnologies

Keasling is responsible for two of the field’s largest and most visible synthetic biology projects, spanning both academic research and commercial development. He is director of the Synthetic Biology Engineering and Research Center (SynBERC) at U.C. Berkeley, funded with $16 million from the National Science Foundation and $4 million from the biotech industry and participating universities.

Amyris, which he co-founded, is developing synthetic microbes capable of producing novel pharmaceuticals, renewable fuels and specialty chemicals. SynBERC and Amyris, along with OneWorld Health, were Gates Foundation grantees for the development of synthetic microbes to produce artemisinin, an anti-malarial compound.

5. U.S. Government

The U.S. government is a primary driver of the nascent industry of synthetic biology. Several agencies have each committed several millions in taxpayer dollars to synthetic biology researchers and organizations, most of which is directed toward specific applications. These include the NIH, including the National Cancer Institute, the National Institute for Allergy and Infectious Diseases, the National Institute of General and Medical Sciences, the National Institute of Biomedical Imaging and Bioengineering, the NIH Roadmap Program, the Nanomedicine Program, and the NIH Cancer Biology Training Grants Program.

The Department of Energy is funding research and development into synthetic organisms to produce biofuels and clean up pollution, as well as explorations into societal consequences such as the relationship of synthetic biology to intellectual property law. The Department of Commerce’s Advanced Technology Program has awarded a grant for the development of synthetic microbes to convert sugars into plastic. The NSF also has committed several millions of dollars to synthetic biology research, primarily to academic institutions.

6. J. Craig Venter: founder, Synthetic Genomics, Inc., and the J. Craig Venter Institute

Venter is still best known for his role in mapping the human genome, but his personal ambition, combined with his ability to draw worldwide media attention, has placed his organizations’ activities at the center of the synthetic biology field. He and Drew Endy are generally the scientists of record when questions about the risks of synthetic biology are raised by outsiders.

Venter’s activities are also the most visible example of the fluid financial arrangements that typify synthetic biology. His privately held company, Synthetic Genomics, is developing synthetic genomes and organisms for commercial applications in renewable energy and bioremediation—based on research done under the auspices of his own non-profit research institute, the J. Craig Venter Institute. The institute, which is funded by government grants as well as by Synthetic Genomics, is focused on trying to develop a minimal cell in order to build a new cell and organism with optimized functions. Synthetic Genomics’ president is Aristides Patrinos, former director of the Office of Biological and Environmental Research for the DOE, which made significant investments in synthetic biology and, more specifically, in Venter’s projects during the period when Patrinos was at the helm.

7. Venture Capital Firms

Venture capital may be more responsible for driving the creation of a synthetic biology industry than are the scientific discoveries coming from the research community. At the time Codon Devices received its first round of venture capital, for example, its co-founders and principals (named above) were basically the entire roster of synthetic biology researchers in the world. A handful of well-known venture capital firms, primarily those that have been involved in early-stage science and technology investments in Silicon Valley and in Cambridge-based startup companies, have already established a beachhead in the synthetic biology area. These firms include Alloy Ventures, Khosla Ventures, Kleiner Perkins Caufield & Byers, Mohr Davidow, and X/Seed Capital.

Notes

[1] A base pair refers to the two nucleotides that form a “rung” of the DNA ladder. The number of base pairs is used to describe the length of a DNA strand. DNA sequencing is the process of determining the exact order of the base pairs that comprise individual genes as well as whole genomes. DNA synthesis is a natural cellular process that replicates DNA, but as used here refers to artificial, chemical replication.

[2] James Newcomb, Robert Carlson, Steven Aldrich, Genome Synthesis and Design Futures: Implications for the U.S. Economy (Cambridge, MA: Bio Economic Research Associates, 2007).

[3] The ENCODE (ENCyclOpedia of DNA Elements) Project, available at http://www.genome.gov/10005107 (accessed August 18, 2008).

[4] Committee on Biological Confinement of Genetically Engineered Organisms, “Biological Confinement of Genetically Engineered Organisms” (National Research Council, 2004).

[5] Holger Breithaupt, “The engineer’s approach to biology,” EMBO Reports, 7(1)(2007): 21-24, available at http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1369239 (accessed August 8, 2008).

[6] Elizabeth Pain, “Getting Ready for Synthetic Biology,” Science Careers, October 17, 2008, 10.1126/science.caredit.a0800152, accessed at http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2008_10_17/caredit.a0800152.

[7] Arti Rai and James Boyle, “Synthetic Biology: Caught Between Property Rights, the Public Domain, and the Commons,” PLoS Biology, March 13, 2007, available at: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pbio.0050058&ct=1 (accessed August 8, 2008).

[8] Breithaupt, “The engineer’s approach to biology.”

[9] The ETC Group, “Extreme Genetic Engineering: An Introduction to Synthetic Biology” (Ontario, Canada, 2007), available at: http://www.etcgroup.org/en/materials/publications.html?pub_id=602 (accessed August 18, 2008).

[10] National Science Advisory Board for Biosecurity, “Addressing Biosecurity Concerns Related to the Synthesis of Select Agents” (Rockville, MD: National Institutes of Health, 2006).

[11] A lengthy discussion of this issue can be found in Intervention: Confronting the Real Risks of Genetic Engineering and Life on a Biotech Planet, Chapter 6, “Politics, Science and Substantial Equivalence” (Hybrid Vigor Press, San Francisco, 2006).

[12] European Commission, “Synbiology: An Analysis of Synthetic Biology Research in Europe and North America: Output D3: Literature and Statistical Review,” European Commission FP6 Reference: 15357 (2005), pp 28-40, available at: http://www2.spi.pt/synbiology/documents/SYNBIOLOGY_Literature_And_Statistical_Review.pdf (accessed August 18, 2008).

[13] National Science Advisory Board for Biosecurity, “Addressing Biosecurity Concerns Related To The Synthesis Of Select Agents.”

[14] Michelle S. Garfinkel, Drew Endy, Gerald L. Epstein, Robert M. Friedman, “Synthetic Genomics: Options for Governance,” (Rockville, MD, Washington, DC, Cambridge, MA: J. Craig Venter Institute, Center for Strategic and International Studies, Massachusetts Institute of Technology, 2007), available at: Available at http://www.jcvi.org/cms/fileadmin/site/research/projects/synthetic-genomics-report/synthetic-genomics-report.pdf (accessed August 18, 2008).

[15] Paul C. Stern, Harvey V. Fineberg eds., Understanding Risk: Informing Decisions in a Democratic Society (Washington, DC: Committee on Risk Characterization, National Academy of Sciences: National Academy Press, 1996).

[16] Denise Caruso and Baruch Fischhoff, principal investigators, “Understanding Genomic Risks: An Integrated Scenario and Analytic Approach” (Washington, DC: National Science Foundation Award No. SES-0350493, 2006).

[17] European Commission, “Synbiology: An Analysis of Synthetic Biology Research in Europe and North America.”

[18] Seattle Biomedical Research Institute, press release: “Sbri Receives $19.4 Million HIV/AIDS Research Grant From Gates Foundation” (Seattle, WA: 2006), available at: http://www.sbri.org/news/2006/releases_06/SBRI-Receives-$19.4M-Gates-Grant-for-HIV-Vaccine-Research.pdf (accessed August 18, 2008).

Americans get the importance of science and technology.

Because the American people are not dense. Despite all the news stories about the last-ditch efforts to keep creationism in our public schools, Americans know which side their bread is buttered on, and that side is science and technology. They can see on television that science and technology are fueling the economies of Europe and Asia. Science and technology will create the good jobs in the United States and will maintain the country’s preeminence in the 21st century. That is why the fact that our kids are falling behind the rest of the world in science literacy is viewed with alarm and a fair degree of nervous joking—Americans get the importance of science and technology.

The public also understands that solutions to some of the major challenges this nation and the entire world face—affordable fuels, global warming, controlling highly infectious diseases, growing sufficient and nutritious food, reducing pollution, cleaning up the oceans and improving transportation, all depend on science and technology. And while the public may not fully appreciate the fact that there have been breathtaking bursts of knowledge in areas such as genomics and neuroscience resulting from heavy taxpayer-supported government funding, they can easily understand that it would be foolish not to make the resources and incentives available to move this new knowledge into practical application in terms of jobs and better health as rapidly as possible.

So in the spirit of three is about as far as you can get (but cheating a little to cover all the areas I am hoping to get on the next administration’s radar) here are six things: three in health and three in science and technology that the next administration ought to argue for vigorously and fund generously during its first term.

Health

Modest but ethically important reform

Most discussions of our strained health care system focus on proposals for single-payer systems, universal health care, and the value of markets and choice. But consider this: the American health care system accounts for about 17 percent of our gross national product, and this inordinate expense is straining industrial productivity and cannot be justified in terms of what we get for our money.

Healthcare expenses affect every level of U.S. industry. For large corporations health care costs mean higher prices on our products along with massive “legacy costs” to insure retired employees. For small business owners healthcare expenses make it impossible both to hire candidates they would otherwise take or to sufficiently incentivize inefficient workers to move on, damaging productivity. Some economists maintain that as many as 42 million U.S. jobs are “susceptible” to offshoring in a future where technology allows the more efficient transfer of jobs and employee health care costs are far less.

As nearly every politician recognizes, something must be done. But the new administration needs to understand that a drastic overhaul of the gargantuan, money gobbling, bloated mess that passes for American health care is not going to fly. There are just so many stakeholders in the hugely inefficient, highly inequitable, but incredibly lucrative broken system that we now have to change it quickly.

The new president should talk boldly but move slowly. Praise the drive toward some day achieving universal coverage, but accelerate change by focusing political momentum on children—the group most likely to command ethical empathy across the political spectrum. The new administration should come up with a proposed basic package, including dental, hearing and eye care, for every American child. Prenatal and post-natal care for every mom ought be there as well.

Of course we need universal coverage for basic health care, but the place to start in practical terms is with those under eighteen years of age. Millions of American children lack health insurance. Not only do they deserve it, but they are the moral key to insuring the rest of us. Show success with kids and the rest will follow.

Stem cell research is great but…

Way, way too much political energy has gone into the embryonic stem cell issue. Working with embryonic stem cells is a very exciting area of biomedical research but it is hardly the only area; nor is it the one that will have guaranteed practical payoffs any time soon. All the new president needs to do is flip the Bush administration restrictions on federal funding, which are inconsistent and wildly unpopular; gin up a new federal panel at the NIH to make sure that oversight of all stem cell research is comprehensive, including all early animal and human trials public and private, transparent, and standardized among the states; put some Federal money into the pot; and get out of the way. The stem cell scientists—adult, fetal, embryonic, induced, and cloned—will take it from there.

America needs much more funding of basic research in genomics, proteomics, and bioinformatics. The “ics” hold the future in terms of mining the little we now know about a whole lot of genes. Without that investment, we will be stuck with half-witted, premature schemes to map our individual genomes—what we can call spitomics—spit-in–a-cup DNA testing. This rapidly growing sector is riding an ill-grounded wave of hype that makes weak, next-to-useless correlations between gene markers and disease states without really having much idea what to tell its customers to do about the risk information that testing companies find.

Fix public health

Our public health system is a wheezing, uncoordinated, underfunded eyesore. It needs to be rebuilt to face the challenges that 21^st century living poses to health, ranging from asthma, to diabetes, to the flu. City and county health departments need federal help across the board. Proactive public health is a key element of our national security. The next administration should demand that Congress pay for it.

So how are we going to fund all this glorious new research? In reality the price tag is not all that big—we hardly spend very much now as a percentage of gross domestic product on basic research in health, technology, and science, especially if you don’t count defense related research. But for those who want a new idea as to funding, here is a bonus suggestion for the next president: It is time to revisit the National Institutes of Health and National Science Foundation budgets and see whether a twist on the Bayh-Dole Act that gives universities incentives to work with industry makes sense.

The NIH budget does not grow in hard times. Congress won’t go there in times of deficit. Private companies wait to see what tax-payer funded basic research looks promising and then develop that, only to sell it back to the taxpayers (you and me) who originally funded the work at high prices. So why not put a 3 percent tax on all products that are generated from NIH, NSF, or other government-sponsored basic research? Keep the core budget there and adjust it to rise in response to inflation, but let American science and the American people really benefit from breakthroughs. In that way the incentives are there to translate basic research into practical products, while at the same time allowing the NIH budget to grow more rapidly without having to whine for more money from Congress every year. Here is a real incentive to universities, think tanks and academic scientists—make real and useful breakthroughs and watch your budget for future research grow!

Science and Technology

A New Push in Agricultural Research

We need safer, healthier food that has far less of a footprint on the environment. Science and technology can help but we need presidential leadership to get us there. To reduce the burden of chemically based farming that depends on fertilizers, herbicides, pesticides and huge amounts of irrigation, we need to apply the genetic revolution to agriculture. Let’s break the link forged by big agribusiness between the “old” chemically based agriculture and genomics and drive forward with a biology-based agriculture that uses genetic knowledge to screen foods and insure their safety; engineers them to make them heartier, more healthful and less oil and chemically-reliant; and creates the next generation of creative farming in cities, estuaries, empty government lands and national forests. And, for those who see creative possibilities in new forms of organic farming and alternative modes of agriculture— working to achieve the “natural” control of pests, better pollination through diversity and using less water through better soil management—give them a bit of money to let them show what they can do as well.

Clean Water

The president needs to understand that clear, drinkable water is going to be a major political issue both in this nation and worldwide very soon. If we have the technology in place to use less, to get more from the oceans, to recapture more from our current industry and farming uses, and ways to identify, track and get rid of microbial pollutants in lakes, rivers, and oceans, we will hold a key foreign policy card. Nanotechnology, micro-sensing technology, better semiconductor technology, and even improved synthetic biology are the tools to get us where we need to go. We just need a president committed to getting us there. If the new president wants to make fast friends in China, the Middle East, India, and Africa he could do worse then by promising to fund and share the science that will lead to more clean water.

Synthetic Biology

The next president and his administration can’t let human hubris about how wonderful our bodies and genes are fool them. We love to think that it is the science of human genetics and human biology that holds the key to our better future. But the fact is, microbes are usually easier to work with than human beings, and are just as useful for making gains in human health, well-being, safety, and security. That means the government should put more money into research in synthetic biology aimed at fighting diseases, making synthetic fuels, eating pollutants, cleaning the oceans and our arteries. As HIV and pandemic flu show, you cannot ever underestimate a microbe. By developing the microbial and synthetic biological science to manipulate these tiny critters, the next president can go a long way toward solving a host of our current headaches.

Keep It Real

In health care and in science and technology, the new administration can make a huge difference by keeping its eye both on what is practical and what is likely to provide the greatest return on investment. These have not always been the watchwords of health and biomedical science policy in the past. There is no need for administrations elected on a promise of “change” to let history repeat itself in the future.

Arthur L. Caplan, PhD is an adviser to Science Progress and the Emanuel and Robert Hart Professor of Bioethics, chair of the Department of Medical Ethics, and director of the Center for Bioethics at the University of Pennsylvania.

SEED’s Science and Society blog has posted video of its Science and Society Series with Drew Endy and Annie-Marie Mazaa of the Committee on Science, Technology and Law at the National Academies. The two discuss synthetic biology: the technology behind it, the current state of research, and the legal and regulatory dilemmas it faces.

Expect only one minute of science and environment coverage in five hours of cable news programming, writes Matthew Nisbet at Framing Science. Taking a hard look at the recently released Pew “State of the Media” report, he explores the lack of science coverage on cable news networks.

How to combat the rise of drug-resistant antibiotics? In the wake of a new study indicating that U.S. citizens often fail to complete prescribed courses of antibiotics or use them to treat the wrong kind of infection, 60 Second Science suggests “education, education, education.”

Derek Lowe at In the Pipeline critiques a proposal from MIT professors Stan Finkelstein and Peter Temin for rethinking the drug development process. In their new book, “Resonable Rx: Solving the Drug Price Crisis,” they suggest breaking up the pharmaceutical business into drug discovery firms and drug marketing firms.

Andrew Plemmons Pratt, Science Progress: Some critics have suggested that the government should slow or heavily regulate research in synthetic biology because of the dual-use dangers: someone with malicious intentions might use it to make pathogens for bioterrorism. Do these organisms actually pose a public safety risk, and do we need to regulate this kind of research?

I don’t see that it poses a significantly greater risk than what we can already do with simpler recombinant methods, or even what occurs naturally.

David Deamer: Ever since recombinant DNA came along, we have had the ability to move potentially dangerous genes from one species of bacteria to another. Previously, the genes were inserted with a plasmid, a small DNA construct, rather than with the whole-genome approach that Venter and his group use. That was possible thirty years ago, so the potential danger has been around that long. For example, someone could insert the botulin toxin gene into E. coli and spray it on a food crop. That would be pretty terrible to have people suddenly coming down with botulism from E. Coli designed to express the gene. By the way, E. coli is a common organism that’s found everywhere, and occasionally a new strain pops up with a toxin that makes people very ill from eating an undercooked hamburger or fresh spinach. The bottom line is that these dangers are already present. We live with risks and we can only go so far in minimizing those risks. As I look toward what might be possible with synthetic biology, I don’t see that it poses a significantly greater risk than what we can already do with simpler recombinant methods, or even what occurs naturally.

SP: Are there constructive uses for synthetic microbes that have not gotten a whole lot of press coverage? Many stories focus on the ability to make bugs that will eat pollutants or produce biofuels. Are there other medical applications that we might not be hearing about?

Deamer: Genentech was the first company to manufacture inexpensive insulin using bacteria, so that’s a good example of an engineered organism making a billion dollar industry possible. And they followed up with other proteins produced by engineered bacteria, including several versions of synthetic growth hormone, Herceptin for breast cancer, TNKase to break up the blood clots that cause heart attacks, and most recently Lucentis to treat macular degeneration that can lead to blindness. So companies are already making money in the medical and pharmaceutical industry by using engineered bacteria.

But the bacteria are engineered by inserting specific genes on a plasmid. The bacteria that actually take up the plasmid and begin to express it are selected for culturing, and suddenly you have a very valuable little organism. Now the problem with using live organisms is that a lot of stuff comes along with not much of the protein that you’re after. Even though they are engineered to over-express the desired proteins, you still end up extracting a relatively small amount of protein from this mass of other proteins that the bacteria need to stay alive and grow, and this can be expensive.

There is another approach to synthetic life. Venter is using a top-down approach in which bits and pieces of existing bacteria are synthesized, then stitched back together and, hopefully, inserted into a second bacterium to make a new species that does what you tell it to do. The other approach is to take those same pieces but put them into an artificial cell. The advantage here is that you can assemble a synthetic version of life from the bottom up and avoid the mass of other stuff that comes along with live organisms. Researchers at a start-up company called ProtoLife, in Venice, Italy, are trying to make this approach work. For instance, it might be possible to incorporate a protein synthesis system in an artificial compartment made of phospholipids with just those genes that code for the protein you want to manufacture. The protein will then be a major product that will require fewer purification steps.

SP: Are there other groups working on this same type of synthetic genome construction they’re doing at the Venter Institute?

I think it is likely that he will get his reconstituted genome to work in living cells this year.

Deamer: No, Venter’s group is the pioneer in top down reassembly of life, but other groups are trying the bottom up approach. Vincent Noireaux and Albert Libchaber at the Rockefeller University broke up E. coli cells, then encapsulated their ribosomes and other enzymes required for protein synthesis in phospholipid vesicles to produce artificial cells. They also included the messenger RNA for green fluorescent protein (GFP), a marker for protein synthesis. After a few hours of incubation in a medium containing amino acids, their cells began to glow green, demonstrating that a lot of GFP was being synthesized inside the vesicles. And Tetsuya Yomo and his colleagues at Osaka University and the University of Tokyo have prepared an encapsulated cascading genetic network that also makes GFP, but the gene is translated all the way from a gene in DNA. I think this approach might finally win the race because it does exactly what you want it to. The system efficiently produces the exact protein you’re after, rather than needing to extract it from a mass of live bacteria.

SP: Venter said that his institute would be disappointed if they did not create an entirely synthetic functional organism in 2008. How fast is this work really moving? When should we expect to see totally synthetic life built on the lab bench?

Deamer: Well, “totally synthetic life”—I think that goes too far. I would call Venter’s approach reconstituted life, rather than synthetic life. But quibbling aside, the results from Venter and his colleagues are truly remarkable, and represent a major advance in biotechnology. I think it is likely that he will get his reconstituted genome to work in living cells this year. The alternative bottom up approach is still years away from a similar success, but there is clear progress being made.

SP: So the next big announcement in synthetic biology would follow construction of an organism that did something functional, like produce large concentrations of specific proteins for a specific use?

Deamer: Yes. At some point we will find a way to assemble a molecular system with the fundamental properties of life: growth, reproduction, evolution, and the use of energy and nutrients from the external environment. We will construct its genome so that it is extremely efficient in producing a desired product. It is even possible that we can get it to evolve toward a desired goal, rather than designing it from scratch.

Life began on the earth perhaps 3.8 billion years ago, and was truly synthetic life in the sense that it self-assembled entirely from non-living components that happened to be available. That is what I would define as synthetic life. When we can discover how life began, how that scaffold of macromolecules came together on the early Earth, it will be an immense step forward in our understanding of life on Earth, a step that goes well beyond engineered and reconstituted life.

SP: So this work will actually teach us something historical about the original emergence of life?

Deamer: Exactly.

Reuters‘s coverage concentrated exclusively on fuel and tied the story to an earlier announcement by General Motors that it had partnered with bioenergy company Coskata, a developer of industrial biotechnologies that employ cellular metabolisms. The Wall Street Journal likewise briefly mentioned producing clean fuels and sequestering carbon.

The BBC focused on the same potential uses of synthetic organisms while incorporating perspectives of scientists and ethicists. Hamilton Smith, a researcher who was part of the Science study, said the research team prefers the word “synthetic” rather than “artificial.” He explained: “With synthetic life, we’re re-designing the cell chromosomes; we’re not creating a whole new artificial life system.” Drew Endy of the Department of Biological Engineering at Massachusetts Institute of Technology, who was not directly involved in the research, said he is optimistic about being able to “routinely design and construct the genomes of any bacteria or single celled eukaryote” within five years. Simon Woods, a bioethicist at the Policy, Ethics and Life Sciences Research Centre at the University of Newcastle, UK, worried that scientists were acting in the complete absence of formal government regulations.

National Human Genome Research Institute director Francis Collins, as reported in Wired Science, called the new study a “methodological tour-de-force,” but cautioned that industrial applications will have to wait years while biologists learn more about what functions specific genes actually perform.

Other news reports raised questions about possible risks of synthetic biological research and even challenged Venter’s intentions.

Rick Weiss in the Washington Post framed the story as a debate between people like Venter who emphasize the benefits of the research, like biofuel production, and critics who emphasize the risks, like biological weapons and unintended environmental damage. In the same article, Harvard Medical School geneticist George Church criticized Venter for conspicuously ignoring or downplaying economic issues, such as the actual financial cost of performing the procedure, which Venter did not disclose.

The New York Times mentioned the same risks as the Post article: human pathogens and ecosystem destruction. In the Times, Jeremy Minshull, chief executive of DNA 2.0, a company that supplied some the nucleic acids used by the research team, was quoted surmising about Venter’s intention: “To some extent, it’s something that was driven by ‘I want to be the first person to do it.’” Also, Jim Thomas, a program manager at the ETC Group, a technology-focused NGO based in Canada, echoed Simon Woods by expressing concern for both the lack of regulation for synthetic biology research and Venter’s broad patent applications covering the Institute’s genetic work. The ETC Group is calling for a moratorium on synthetic biology research so stakeholders can debate its ethical, legal, and social ramifications.

Leo Hickman in Guardian Unlimited invoked Frankenstein, popular science fiction, and the fear of “playing God” to endorse the proposed ban on synthetic biology. The Creation Museum went a step further and claimed that the creation of synthetic life is simply not possible.

UC Santa Cruz Chemistry Professor David Deamer offered a brief history of the research and an overview of the science behind the field in a recent Science Progress article. He situates discoveries in synbio with other major scientific advances like semiconductors, penicillin, and atomic energy. In his assessment, the benefits outweigh the risks, and the risks, at the moment, are not significant: “So far, there are virtually no restrictions on this kind of research, nor should there be, in my judgment….The bottom line is that there are always risks associated with every benefit, and that global human society is too complex ever to exert absolute control.”

Weiss catalogs several applications for synthetically engineered organisms. J. Craig Venter proposes to create microbes that directly produce biofuels. LS9 is a San Carlos, CA company currently growing E. coli that processes sugars into liquid fuel. And DuPont uses “semi-synthetic” bacteria to produce PDO, an industrial chemical useful in a variety of applications, including adhesives, laminates, and polyester fibers. A current medical application produces super-efficient bacteria that generate artemisinin, a malaria drug.

If the danger of malevolent synbio projects is indeed manageable, Weiss points to another possible policy concern—the hazard of anti-competitive hegemony in the field:

Some experts are worried that a few maverick companies are already gaining monopoly control over the core ‘operating system’ for artificial life and are poised to become the Microsofts of synthetic biology. That could stifle competition, they say, and place enormous power in a few people’s hands.

This possibility raises the question: can and should the Federal government regulate ownership of the building blocks of life and the tools with which to manipulate them?

Yet a number of laboratories around the world are attempting to perform a reconstitution of life eerily similar to Frankenstein’s dream, but on a microscopic scale. There is even a name for such science: synthetic biology.

Without a grasp of the science itself any discussion of the policy implications of synthetic biology would be ill-informed.

The history of attempts to fabricate artificial cells that increasingly are approaching the definition of living organisms is complex, compelling, and most of all fast-moving. These efforts have not yet succeeded, but there is reason to believe that the goal may be achieved in the next decade. When someone somewhere on Earth announces that they have been successful, significant public concerns will arise in terms of safety issues, but also because success will challenge deeply held religious beliefs that the synthesis of living organisms should be reserved for a Creator.

Before delving into these serious safety and ethical issues, however, we first need a quick history of synthetic biology to date. The reason: without a grasp of the science itself any discussion of the policy implications of synthetic biology would be ill-informed.

Assembling a system of molecules capable of reproduction was first achieved in 1955 when it was demonstrated by University of California, Berkeley professors Heinz Fraenkel-Conrat and Robley Williams that tobacco mosaic virus could be separated into its coat protein and RNA. Neither component was active by itself, but when mixed together the two parts reassembled into the infectious agent.

Viruses are not considered to be alive in the usual sense of the word, because they can only reproduce themselves using the machinery of a living cell. But a successful reconstitution of viral functions encouraged other investigators to attempt the reassembly of more complex systems. In the 1970s, Cornell University biochemist Efraim Racker was the most successful practitioner of this art, employing detergents such as deoxycholic acid to disperse membranous components of cells. When the detergent was removed, small membranous vesicles formed that resembled microscopic balloons filled with water. Their membranes contained the original components of the cell membranes, albeit somewhat scrambled in their orientation.

Despite the scrambling, Racker and his colleagues were able to reconstitute electron transport reactions and ATP synthesis of mitochondrial and chloroplast membranes. All living cells use some form of electron transport to generate energy, either from nutrients or, in the case of the green chloroplasts of plants, from sunlight. The energy is stored as ATP, the universal energy currency of life. Racker’s success meant that two key activities of living cells had been reassembled in the lab.

The point of this brief history is that relatively complex biological functions can be reconstituted by the self-assembly of their dispersed components.

Similar techniques were soon applied to other structures. For instance, Walther Stoeckenius of the University of California, San Francisco and Dieter Oesterhelt, now at the Max Planck Institute, reconstituted the proton pump of purple membranes isolated from a halophilic bacterial species that uses the energy of a proton gradient to synthesize ATP. In a remarkable collaboration, Racker and Stoeckenius then teamed up to produce a membranous system containing both the proton pump of halobacteria and the ATP synthase of mitochondria, and demonstrated that the hybrid membrane structures could synthesize ATP using light as an energy source.

This paper has often been cited as the publication that finally confirmed chemiosmotic synthesis of ATP, leading to a Nobel Prize in Chemistry for Peter Mitchell of the Glynn Research Laboratories in 1978. Mitchell in 1961 proposed that the primary function of electron transport was to pump up a hydrogen ion gradient across membranes, and that the gradient’s energy was used to drive the synthesis of ATP by the ATP synthase enzyme present in mitochondria, chloroplasts, and bacterial membranes. Mitchell’s chemiosmotic theory is now found in every college textbook of biochemistry.

Later, University of California, Los Angeles biochemist Paul Boyer was awarded the 1997 Nobel Prize in Chemistry for his proposal that the hydrogen ion gradient actually caused part of the synthase to spin at several thousand revolutions per minute as ATP was synthesized, a truly amazing discovery.

The point of this brief history is that relatively complex biological functions can be reconstituted by the self-assembly of their dispersed components. So why not try reconstituting a whole cell? If this turns out to be possible, it will help us untangle what we mean by “life.” Perhaps we might even elucidate the major steps that led to the origin of cellular life nearly four billion years ago.

Let’s first consider what might happen if we disassembled a microscopic living organism and tried to put the pieces back together. We would not use a nucleated cell like an amoeba or a human lymphocyte. Too complicated. Too many moving parts.

Instead we should use a much simpler form of life, such as a tiny bacterium called Mycoplasma, a kind of microbial parasite that requires a relatively rich nutrient environment. Only 482 genes are present in its genome, while more complex bacteria such as E. coli have over 4,000 genes. The human genome, by way of contrast, has nearly 30,000 genes at last count.

The cells of Mycoplasma are bounded by a naked membrane composed of a mixture of lipids, or fatty substances in the form of a bimolecular layer common to all membranes, with a variety of functional proteins and enzymes integrated into the bilayer. Some of the enzymes are responsible for extracting energy from nutrients and using the energy to synthesize ATP, while others are essential transporters of nutrients from the external medium into the cell.

Examples of nutrients are glucose, as an energy source, amino acids as building blocks for proteins, and phosphate for nucleic acids. The interior contents of the cell include a circular strand of DNA having genes responsible for synthesizing proteins required for metabolism. A variety of structural components are also present, including thousands of ribosomes, the molecular machines that synthesize proteins, and hundreds of soluble enzymes involved in metabolism.

What happens when we add a detergent to Mycoplasma? The detergent penetrates the lipid bilayer, which becomes unstable and breaks up into smaller particles containing lipid, membrane proteins, and the detergent molecules. With the membrane gone, the interior components are released. What we see visually is that the slightly turbid suspension of bacteria becomes clear, and if examined with a microscope no cells would be visible. The resulting solution contains all the components of the original living cell, but they have become diluted and disorganized.

Now we can try to reassemble them by injecting a certain amount of order back into the system. This is done by a process called dialysis, in which smaller molecules like detergents leak through a porous membrane while larger molecules remain behind. The same process is used to treat patients with kidney disease. As the detergent leaves, the lipids self-assemble into bilayers that take the form of small vesicles. The membranous boundaries of the vesicles incorporate most of the functional enzymes and transport proteins that were present in the bacterial cell membranes.

Each vesicle contains a random sample of the original contents of the bacterial cell, with one exception: The circle of DNA, the genome that was originally packed tightly into the original living cells, has unraveled and is too large to be captured when the vesicles reassemble. Although there are ways to do it, getting a large chunk of DNA into an artificial cell is going to be a problem for anyone attempting to fabricate synthetic life.

We and others have carried out such experiments. The figure below shows an electron micrograph of one of our preparations, not from Mycoplasma but rather from the lab rat of microbiology, a bacterium called E. coli. Several dark particles can be seen within each vesicle, and these are ribosomes—the ubiquitous protein synthesis machinery present in all living cells and absolutely necessary for all living things.

Ribosomes in reconstituted E. Coli. SOURCE: David Deamer.

Well, is it that easy? Did we reassemble something that is alive?

Several of my colleagues have carried out experiments that bear on this question, including Luigi Luisi at ETH Zurich, also known as The Swiss Federal Institute of Technology; the Yomo research group at Osaka University; and Vincent Noireaux and Albert Libchaber at Rockefeller University in New York. They found that if amino acids and an energy source are supplied to the ribosomes in the vesicles, along with a specific gene for a marker protein called GFP, or green fluorescent protein, then the vesicles begin to glow green when illuminated with UV light.

This means that the ribosomes are functional, and that the vesicles have one of the most fundamental properties of life—they can use genetic information to synthesize a protein. In other words, in a very limited sense, they can grow.

But are they alive?

The answer is no. Even though they can grow, only a single protein is produced, and everything else is left behind. To be truly alive, the vesicles need most if not all of their original 400-plus genes in the form of a DNA strand containing the genetic information required to direct the synthesis of hundreds of different proteins and RNA species, nearly half of which are the components of the ribosomes themselves.

What’s more, the vesicle would need genes for polymerase enzymes so that the DNA could be replicated as part of the growth process, as well as a way for lipid to be synthesized because the membranous boundary must grow to accommodate the internal growth. Transport proteins must also be synthesized and incorporated into the lipid bilayer, otherwise the vesicles have no access to external sources of nutrients and energy.

What’s more, a whole set of regulatory processes must be in place so that all of this growth is coordinated. Finally, when the vesicles grow to approximately twice their original size, there must be a way for them to divide into daughter cells that share the original genetic information.

This description makes it clear why we still don’t understand how life began on Earth. The complexity of a living system is wonderfully intricate, and there is still much to learn about simpler versions of this process that must have occurred as a precursor to life as we know it today, which represents several billion years of evolution.

There is a certain danger in what I just said. Why? Because creationists and proponents of intelligent design seize upon such statements as a scientist’s confession that it is hopeless to try to understand the origin of life, or to make synthetic life. If it is beyond our current understanding, they argue, there must have been a supreme intelligence at work.

I disagree, of course. The creationist viewpoint typically arises from a snapshot of scientific progress, and creationists revel in scientific admissions that there are things we don’t yet understand, thinking that this must somehow be embarrassing for the scientist. Creationists, of course, do know how it all happened: God did it. End of story.

Now we return to the question in the title of this essay: Should we do it?

Scientists are not satisfied with answers that represent a statement of faith, but want to keep on asking questions. We are much more optimistic about the chances that we will be able to use our knowledge of physics, chemistry, and biology to assemble a living system. The reason is that we don’t see just a snapshot of our current state of knowledge with its unanswered questions. Instead, we perceive a movie of progress over the past half century. We see how vast dark tangles of ignorance have given way to a deep understanding of life’s mechanisms.

Just for starters, we now know the sequence of three billion bases in the human genome, an achievement that was undreamed of when James Watson and Francis Crick established the double helix structure of DNA in the early 1950s. We can manipulate bacterial genomes at will, cause stem cells to develop into specific tissues, even produce clones of sheep, dogs, cats, and other mammalian species. Given the momentum of scientific progress, it seems entirely plausible that in the next 50 years we will be able to reassemble bacterial cells from a parts list, and perhaps even produce a new form of life, a second origin of life, but this time under laboratory conditions.

Now we return to the question in the title of this essay: Should we do it?

The public has watched and been astonished by the powers unleashed by scientists. Virtually every revolutionary advance in recent history can be traced back to a few individual scientists following a trail of intuitive ideas invisible to others, driven by a passionate curiosity about how things work. Marie Curie and Henri Becquerel gave us radium, uranium, and atomic energy. William Shockley and his colleagues, all Nobelists, demonstrated the odd electrical properties of silicon that led to a vast semiconductor industry; Alexander Fleming noticed a mold that inhibited bacterial growth, giving us penicillin, the concept of antibiotics, and the pharmaceutical industry.

So who is going to give us synthetic life? Craig Venter is trying. He and his colleagues at the J. Craig Venter Institute in Maryland have already sequenced Venter’s DNA, and he is the first human being in history to reveal his genome, all three billion base pairs, for public scrutiny. They have discovered the minimal number of genes required for a simple bacterium to grow and reproduce, and recently transferred a complete genome from one bacterial species to another—equivalent to a microscopic brain transplant.

Is this an ethical pursuit? Should there be laws against tinkering with life this way?

The immediate concern, of course, is the balance between valuable new knowledge and public safety. On the plus side, we might be able to design forms of artificial life that can make vast supplies of inexpensive useful products available. In a primitive way, we already do this. Biotechnology industry giant Genentech Inc., for example, uses genetically modified bacteria to make human insulin and other proteins. Indeed, most of the major pharmaceutical industries brew up vats of microorganisms to produce antibiotics.

Other companies, including Venter’s, are trying to grow specialized bacteria that can produce energy sources such as hydrogen gas. But these are only slightly modified versions of existing forms of life, and it is a costly and complex process to isolate a small amount of desired product from a mass of bacterial protein.

The goal of synthetic biology is to design a simplified version of life that produces the desired product with high efficiency and uses an abundant energy source such as sunlight, or cellulose derived from agricultural waste. So far, there are virtually no restrictions on this kind of research, nor should there be, in my judgment. But bioethical principles require us to look further, to weigh risks and benefits.

So there is no way to control attempts to produce artificial life.

What are the risks of learning how to make artificial life? Given the example of HIV and the AIDS epidemic, it’s not difficult to look ahead to potential risks. The HIV virus is an accident of nature, and we can trace its origin back to the consumption of bush meat–most likely chimpanzees–in Africa, then to one or a few infected individuals traveling to Haiti who initially spread the virus in the 1960s, and finally to the outbreak among the gay community and drug users in the early 1980s.

The public—the taxpayers who support most research—will wonder about the chances that an accident might happen in the laboratory. After all, the primary property of life is reproduction and evolution. What if we make an artificial organism that escapes, evolves, and reproduces, using the human body as a source of energy and nutrients? As often happens, writers of science fiction have examined such possibilities, and Michael Crichton describes one such scenario in his novel Prey.

Even worse than an accidental release, what about the possibility that a terrorist group will design a synthetic bacterium that is passed between human beings, multiplies in the gut, and produces botulin toxin? Or a virus like HIV that can be transmitted like influenza, rather than as a sexually transmitted disease. Just imagine the public outrage if the AIDS virus were discovered to be someone’s invention, rather than an accident of viral evolution in the wild. It can even be argued that the Department of Homeland Security should carry out research in synthetic biology in order to find ways to defend against such threats.

The bottom line is that there are always risks associated with every benefit, and that global human society is too complex ever to exert absolute control. An example is stem cell research. For political reasons, bowing to far-right Christian fundamentalists, the Bush administration banned the use of federal funding to develop new embryonic stem cell lines. South Korea and Japan simply took this as an opportunity to jump ahead in the race of discovery, and Californians voted to provide $3 billion of state taxpayers’ money to support such research.

So there is no way to control attempts to produce artificial life. All we can do is look ahead to the potential dangers and try to provide thoughtful guidance to researchers and policymakers so that they will consider possible dangers and be aware of public concern. Most research in this area is carried out using grants from federal agencies such as the National Institutes of Health, the National Sciences Foundation, and the National Aeronautics and Space Administration, and all proposals undergo peer review.

We must make this process as transparent as possible, and we must have open discussions of risks and benefits so that the referees can make informed decisions about the value of the research, and potential dangers.

In my judgment, the search for a method to reassemble life is still in its initial curiosity-driven phase. Today, there is no reason to do anything but cheer on the few scientists who are pioneers in this unexplored territory. Risks are low and acceptable, primarily because evolution has had several million years to throw viral and bacterial pathogens at human existence. Even though our immune systems have lost some battles, we are still winning the war.

I would expect that a laboratory version of artificial life, if released into the wild, would be like a helpless young mouse in a world filled with hungry and ruthless predators. But that’s my judgment call, and now it’s time to hear from everyone else. Should we do it?

David Deamer’s primary research area concerns the manner in which linear macromolecules traverse nanoscopic channels. A second line of research concerns molecular self-assembly processes related to the structure and function of biological membranes, and particularly the origin and evolution of membrane structure.