US Competitiveness in Synthetic Biology

Abstract

Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative—additional investments will expand markets—but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

Synthetic biology is an emerging new technical field that aims to make biology easier to engineer and more amenable to rational design, so that biological traits, functions, and products can be programmed like a computer. The concept of engineering biology is not a new one, nor is synthetic biology the first instance in which biology has been declared engineerable.¹ Stephane Leduc wrote about the concept in the early 1900s.² In 1974, the renowned cancer biologist Waclaw Szybalski described then-current work on molecular biology as the “descriptive phase,” adding that the real challenge will begin “when we enter the synthetic biology phase of research in our field. We will then devise new control elements and add these new modules to the existing genomes or build up wholly new genomes.”^3(p23) Though what is now termed synthetic biology is not wholly distinct from previous studies of genetic engineering, the ability to fruitfully accomplish bioengineering is much greater now than it has been at any other point in history. Thanks to advances in computing power; the ability to rapidly, reliably, and inexpensively synthesize long tracts of DNA; new tools to reliably edit genomes; an increased understanding of biological systems; and the enthusiasm of young scientists who want to enter the field, synthetic biology is a new field and a new phenomenon, which proponents believe could revolutionize medicine and manufacturing.^4-7

Synthetic biology encompasses widely diverse aims, making it difficult to draw boundaries for the field. For example, synthetic biology applications have included making a synthetic version of an anti-malarial compound that is difficult to harvest from nature; synthesis of influenza vaccines that could be produced in a shorter time than by traditional methods; manufacturing standard biological parts that can be assembled into genetic machines, including measurement devices, inverters, or logic devices; investigations into how life emerged on earth through the development of protocells; the synthesis of a bacterial cell; and the development of cell factories to produce biofuels and other compounds.^8,9 In addition to synthetic biology being its own discipline, it has also brought about new tools to manipulate the genomes of biological organisms, which are used by scientists in disparate fields and in a variety of biotechnology companies.

The field shows a great deal of promise. According to the US National Bioeconomy Blueprint (2012), synthetic biology and related biotechnologies “can allow Americans to live longer, healthier lives, reduce our dependence on oil, address key environmental challenges, transform manufacturing processes, and increase the productivity and scope of the agricultural sector while growing new jobs and industries.”¹⁰ However, the advent of synthetic biology also poses risks, which have generated a great deal of attention from national security experts and the US government since the inception of the field. The field is creating new tools for genetic manipulation of biological organisms and making them more accessible worldwide; these tools could be misused to make a biological weapon or inadvertently cause a consequential accident. Concerns about these risks have resulted in numerous US government actions over the past decade, including guidance for DNA synthesis companies to limit unauthorized production of pathogens; an examination of the ethical risks and regulatory challenges inherent in the synthetic biology field by the Presidential Commission for the Study of Bioethical Issues in 2010; an examination of the biosecurity risks by the National Science Advisory Board for Biosecurity, a federal advisory committee created to address issues related to biosecurity and dual-use research; an FBI “see something, say something” program to reach out to scientists at universities as well as amateur scientists to report on intentional misuse; and a recent moratorium on certain areas of influenza infectious disease research (so-called “gain of function research”) while the risks and benefits are analyzed by advisory committees to the US government.^11-16

While concerns about the safety or deliberate misuse of synthetic biology are appropriate, these prospective scenarios do not span the full range of risks that the development of the synthetic biology field may pose to US national security. There is another scenario that would have serious negative consequences to US national security that should be considered by US policymakers and experts and should inspire action: that the United States may lose its competitive edge in synthetic biology and related technologies. While the synthetic biology field was pioneered in the United States, and the United States is currently the leader in these technologies, other nations are investing heavily in these technologies in hopes of capitalizing on the field's progress, boosting their economies, and leading the field. Some, like China, India, and the UK, have even developed specific synthetic biology roadmaps for development.¹⁷ At the same time as there is heavy investment in synthetic biology by other nations, there is mounting concern that the competitive position of US life sciences is diminishing.^18,19

If the United States were to lose its competitive edge in synthetic biology and related technologies, there would be serious consequences for national security. Some negative effects would be strictly economic, resulting in a declining environment for businesses and workers to be productive in synthetic biology–related industries in the long term.²⁰ This is important for national security because, as described in the US National Security Strategy (2015), “In addition to being a key measure of power and influence in its own right, [a strong economy] underwrites our military strength and diplomatic influence. A strong economy, combined with a prominent US presence in the global financial system, creates opportunities to advance our security.”²¹ Current forecasting would suggest that a loss of economic opportunities in synthetic biology could be immense: Fidelity Investments describes synthetic biology as “the defining technology of next century” for global investments.²² In 2012, the World Economic Forum ranked synthetic biology as the second key technology for the 21st century, after informatics.²³ According to BCC research, a market analysis company, the synthetic biology market reached nearly $2.1 billion in 2012 and $2.7 billion in 2013. They expect the market to grow to $11.8 billion in 2018 with a compound annual growth rate of 34.4% over a 5-year period from 2013 to 2018.²⁴

Losing competitiveness in synthetic biology could also limit specific security applications on the horizon that are essential for national defense. These include the development of medical countermeasures for responding to biological, chemical, or radiological weapons threats and new approaches to diagnostics. A US Department of Defense (DoD) report described how synthetic biology could bring major advances to the development of high-performance sensors, sensors for unusual signatures, clandestine sensing, and high-performance materials for national defense; these applications would not likely be available to DoD based on private sector funding alone.²⁵ Synthetic biology may also offer the possibility for distributed manufacturing so that critical supply chains are less vulnerable to disruptions.

Synthetic Biology, Governance, and US Participation

These next several years will likely be formative in setting the “rules of the road” for emerging synthetic biology research. Yet, the United States may be disadvantaged and limited in its ability to actively participate in fundamental conversations about the governance of synthetic biology if US experts are not technological leaders in synthetic biology, as the shaping of synthetic biology governance will be dominated by the nations and their experts who are at the leading edge of technology development. This is because formal regulations or standards usually lag well behind the development of new technologies. For a new technical area, regulations are often preceded by the development of standard practices in a field, as well as cultural expectations and safety measures. These expectations and agreements build on previous sets of regulations but take new technical possibilities and dangers into account. The rules are often created by those who are most intimately familiar with the technologies—often, the scientists who are performing the work at the leading edge of development.

In the biological sciences, the most well-known example of scientists calling attention to nascent dangers in their field and setting the standards for scientific practice occurred when the field of recombinant DNA biology was new. In a letter published in Science in 1974, leading scientists and Nobel laureates recommended that certain types of recombinant DNA experiments—those with toxins, oncogenic viruses, and antibiotic resistance—should be off limits until their safety could be evaluated and assessed in a conference held a year later.²⁶ That conference, held at Asilomar, California, in February 1975 and attended by scientists, government officials, and members of the press, led to a lifting of the moratorium in 1976, as well as the creation of a new regulatory system for recombinant DNA work funded by the US government.²⁶ Efforts of the scientists to self-govern may well have forestalled restrictive national legislation.²⁷ Asilomar now symbolizes scientists' attention to the public's concerns, as well as the scientific community's capacity to self-govern.

A more recent example of self-governance can be found in a synthetic biology application: commercial DNA synthesis. Companies that sell DNA synthesis products now screen their orders to determine whether a customer is ordering genetic material for dangerous pathogens and to block orders if the customer is not authorized. This screening system was developed in large part through self-governance of the commercial suppliers and interested scientists, with funding from the Alfred P. Sloan Foundation, and was eventually put into formal guidance from the US Department of Health and Human Services in 2010.^11,28

In the synthetic biology field, there are other applications at the leading edge of development that will require governance measures to be safely and ethically applied, and some scientists have already stepped in to propose self-governance measures to deal with them. One example is the development of gene drives, which are systems that can spread a particular gene throughout a population with non-Mendelian inheritance—that is, much faster than would occur naturally.²⁹ These have become much easier to construct using a new gene-editing technique—clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 or Cpf1)—which allows sections of DNA to be searched for and replaced in a matter roughly analogous to editing a document in Word. Some scientists have proposed using gene drives to change the DNA of mosquitoes to make them resistant to malaria. Such a project could decrease the prevalence of malaria, which currently kills more than 600,000 people—mostly children—per year. Yet, this technology could be misapplied or result in a consequential accident should the genes spread to other species or cause other unintended effects. Those scientists who have been leading the development of gene drive and gene editing technologies have also taken the lead in thinking about the safety consequences, and they have been developing a series of commonly agreed upon safeguards for laboratory research into gene drives, such as using a combination of multiple stringent confinement strategies, as any single confinement strategy could fail.²⁹ Scientists have also put forward ideas for how to safely use them outside of the laboratory.³⁰

Another contentious application of synthetic biology that will require careful planning and safety standards is human germline editing, wherein modifications to sperm or egg DNA would not be applied to just one person, but to all their progeny. A group of interested and involved scientists met in Napa, California, to consider the ethical and safety ramifications of this work; the meeting was convened by Jennifer Doudna, one of the molecular biologists credited with developing the CRISPR/Cas9 tool. The meeting was intended to discuss the “scientific, medical, legal, and ethical implications of these new prospects for genome biology,” and they identified steps so that this technology could be performed “safely and ethically.”^31(p36) In their consensus paper, published in Science, they recommend that the practice of germ-line editing be strongly discouraged for now, that forums be held in which this application can be discussed more broadly, and that foundational research that does not cross the line into embryo modification be encouraged.³¹ The National Academies of Science also launched an initiative to recommend guidelines for the new genetic technology, to explore the scientific, ethical, and policy issues associated with human gene-editing research.³²

Determining what the “red line” is for allowable, critical, or ethical applications of synthetic biology, as well as how much safety data are required before pressing ahead, will always be a challenging exercise, and not all scientists, experts, and observers will agree. Tension over what is acceptable to pursue has already come up for germline editing, after a Chinese research group reported that they used CRISPR techniques to modify human embryos.³³ (And there are at least 4 additional research groups in China known to be pursuing gene editing in human embryos.³⁴) While the standards or expectations set by the scientific community will be impossible to enforce in an international context, the scientific community does set boundaries; those who flout those standards have to justify their actions in the international practice of science, and those boundaries and expectations are set by the leaders in the field. In the case of germline editing, the Chinese research was rejected by top-tier scientific journals Nature and Science, in part because of ethical objections.³⁵

Self-governance of science has its critics, who are justifiably skeptical that scientists can be trusted to govern their own research fairly and who question the effectiveness of this approach in an international context, as the embryo editing example illustrates. However, self-governance is not the sole mechanism of governance in this area, as many foundational aspects of biotechnology and laboratory practice are already tightly regulated, and also because in forming new rules there is often a complex interplay among scientists, journalists, and policymakers to bring about new guidelines. In the case of DNA synthesis guidance, while there was substantial work done by scientists and interested parties to prevent misuse of DNA synthesis and promote screening, the issue became more salient, requiring immediate action, after a journalist ordered a small segment of DNA that encoded the smallpox virus.³⁶ Still, feasible alternatives to self-governance are limited when technologies are still in the early stages of development, particularly when the applications are of broad interest, generating funding from private companies and multiple national governments, when the work is pursued in many places internationally, and when the technologies have great potential for tangible benefits to health and medicine. In addition, the amount of technical knowledge required for understanding the implications of new research and what can be done to ameliorate negative consequences makes it challenging even for scientists in distinct disciplines to evaluate research outside their expertise, because understanding the technical details inherent in the technology are critical both for identifying problems as well as proposing solutions.

There are additional applications of synthetic biology that have already generated conversations about governance within the scientific community—such as rescuing a species on the path to extinction; or even using synthetic biology for “de-extinction,” to bring back a species that was lost because of human hunting or negligence; or brewing opiates by fermentation in a process not unlike brewing beer.^37-39 These applications have already sparked scientific involvement in discussions of what is technically possible and what rules should be developed. In 5 to 10 years, the list of applications that will require expert opinion and involvement to set expectations, standards of practice, and self-governance may well be very different, just as consequential, and require technical experts to take the lead in setting norms and safety standards. If US scientists, policymakers, and institutions would like to have some say in what is decided, they will need to be at the forefront of those technologies.

US S&T: Evidence of Promise and Decline

The United States is currently a leader in synthetic biology, as well as biotechnology and biomedical research, and it is the focus of a great deal of private sector investment; these investments may help to bring at least 100 products to the market in the near future.^17,40 According to a DoD report, the US government also provides at least $220 million annually toward synthetic biology R&D, with investments from the Department of Energy, the National Science Foundation (NSF), the DoD (including DARPA), the National Institutes of Health (NIH), and the US Department of Agriculture (USDA).²⁵ An analysis from the Wilson Center found that between 2008 and 2014, the US government invested a total of $820 million in synthetic biology research, with DARPA funding nearly $110 million in 2014.⁴⁰ Indeed, synthetic biology researchers in the United States have largely relied on DARPA funding, such as in their Living Foundries program, which aims “to create a revolutionary, biologically-based manufacturing platform to provide access to new materials, capabilities and manufacturing paradigms for the DoD and the Nation.”⁴¹

The United States does not have a specific synthetic biology technology roadmap, but on April 27, 2012, the Obama administration released their National Bioeconomy Blueprint, “a comprehensive approach to harnessing innovations in biological research to address national challenges in health, food, energy, and the environment.”¹⁰ The blueprint identifies the administration's priorities to grow the bioeconomy through increased investment in research and development, expansion of public-private partnerships, and regulatory reform and, in numerous instances, specifically mentions the enormous promise of synthetic biology. While the government programs and initiatives listed in the Bioeconomy Blueprint were already in progress, the blueprint served as a sign of federal commitment to developing the biological sciences as a component of the US economy.⁴²

The United States also has a robust bioeconomy, which includes synthetic biology and related technologies. Defining the economic impact of synthetic biology is difficult, as “traditional” biotechnologies are also taking advantage of pervasive synthetic biology techniques. Looking at the bioeconomy as a whole, Robert Carlson, an industry analyst, found that products derived from biology contributed an estimated $350 billion to American GDP in 2012, and the “bioeconomy” grew 15% annually and accounted for nearly 7% of total US GDP growth in 2011 and 2012.⁴³ Engineered organisms led to products worth more than $350 billion per year to the US economy. DuPont, Pfizer, Bausch & Lomb, Coca-Cola, and other Fortune 500 companies either make or use products derived from engineered organisms, including food, clothing, medicines, and beauty products.²⁵ For example, DuPont has been producing commercial quantities of the polymer 1,3-propanediol from engineered bacteria since 2006, which is 37% of the material in their Sorona fibers—used for everything from carpets to car interiors.⁴⁴ Some investors forecast the possibility of billions of dollars of growth in American manufacturing through the biotechnology sector, including at the Goodyear Tire & Rubber Company, DuPont, Archer Daniels Midland, and Solazyme.⁴⁴

Yet, in spite of clear US leadership in synthetic biology, there are well-documented concerns about the United States falling behind in biotechnology and in science more generally, as well as concerns about falling US biomedical research budgets, STEM (science, technology, engineering, and mathematics) workforce decline, and outsourcing by international pharmaceutical and biotechnology companies, which are applicable to synthetic biology as well. Global indicators for the biosciences and biotechnology, including R&D outputs as well as shares of the global pharmaceutical industry, higher education, and workforce, are showing what NIH called an “erosion of the competitive position of the U.S. life sciences industry over the past decade.”¹⁹ China will overtake the United States in R&D spending by 2020.¹⁹ In 2007, China overtook the United States in the number of doctoral degrees awarded in the natural sciences and engineering.⁴⁵ Europe is thought to be the fastest growing market for synthetic biology products, and the UK is considered to be one of the most innovative and dynamic, and healthcare industries there are expected to grow in the future.²⁰

US students in synthetic biology have been affected as well, as seen in the international Genetically Engineered Machine (iGEM) competition. This competition pits teams of synthetic biologists (primarily undergraduates) from all over the world in competition to engineer biological systems and operate them in living cells. It began as a small class at MIT in Cambridge, Massachusetts, in 2003 and has grown to more than 2,000 international participants and more than 16,000 alumni.⁴⁶ In 8 of the past 10 years, US student teams have failed to win “in part because of a lack of laboratory facilities” and other support.^18(p29)

In a DoD report from the Office of Technical Intelligence, Office of the Assistant Secretary of Defense for Research and Engineering, dwindling human capital was identified as an obstacle to DoD operating effectively and efficiently in the future: “There are few highly-experienced program managers in the Department, few leading scientists, and even fewer individuals in uniform with deep knowledge of the [synthetic biology] field. The lack of uniformed expertise is particularly troubling.”^25(p20)

In contrast to other industries that require substantial natural resources, such as arable land, oil, or natural gas, synthetic biology and related technologies have few barriers to entrance, and emerging markets can become competitive quickly. Major gains have been made rapidly in several nations by changing policies and investments. Though there are several countries making substantial strategic investments in synthetic biology, the example of China is most notable. The Chinese Academy of Sciences includes synthetic biology in its Innovation 2050: Technology Revolution and the Future of China Roadmap.⁴⁷ An example of China's substantial investments in synthetic biology is its support of the Beijing Genomics Institute (BGI), a company located in the city of Shenzhen. It is the world's largest genetic research center, with more sequencing capacity than the entire US and about one-quarter of the total global capacity.^48,49 In 2013, BGI purchased the Mountain View, California–based company, Complete Genomics, 1 of the 2 leading companies in the world that make equipment for sequencing DNA, further increasing BGI's dominance in the sequencing market. Previously known solely for their speed and proficiency in sequencing genomes, the company is starting to diversify and innovate, making several commercial diagnostic tests. The comprehensive database of sequencing information they have developed—they have sequenced many hundreds of different types of bacteria; crops such as rice, soybeans, and cucumbers; and dozens of animals including the giant panda; as well as human genomes—is seen as a springboard for new discoveries, as well as the development of new drugs and therapies. BGI has also been helpful in international science efforts, playing a role in the Human Genome Project and identifying the foodborne Escherichia coli outbreak in Germany that infected nearly 4,000 people, killing 53.^50,51

China's research system still draws attention for its ethics problems—including fraudulent results, plagiarism, junk patents, and unsafe or ineffective medical practices—but experts believe that the Chinese research system is changing and becoming more internationally competitive.^52,53 This change is due in part to China's successful efforts to lure back Chinese researchers who were trained and/or employed in the United States, offering them bigger budgets and greater research freedom than they would have in the United States. In the case of BGI, international collaborations are integral to their success and include partnering with the Gates Foundation as well as hospitals and universities in the United States and Europe.⁵⁴

The UK has also looked to synthetic biology for economic growth and other benefits. A roadmap for synthetic biology was released in 2012, and to date the UK government has invested approximately £200 million for research and the creation of several synthetic biology research groups across the country.^55,56 In a 2012 study that mapped the scientific landscape for synthetic biology, the UK was second only to the United States in having its scientists author publications on synthetic biology.⁵⁷ The UK is also taking steps to dissociate synthetic biology from the controversies surrounding genetically modified organisms (GMOs). At the most recent world conference on synthetic biology, held at Imperial College, London, in 2013, a minister from the House of Commons told the assembled scientists, referring to GMOs, that the UK would not become “a museum of twentieth century technologies in the twenty-first century.”⁵⁸ GMO restrictions are a competitive hindrance in UK participation in the field of synthetic biology and in biotechnology in the UK and EU more generally.

Steps to Greater US Competitiveness

Measures aimed at boosting competitiveness in science and technology generally are broadly applicable for synthetic biology and should be pursued by the US government. These initiatives would include increased basic research funding with minimal fluctuations from year to year, workforce development, and STEM education initiatives, as well as financial incentives to start and fund biotechnology and synthetic biology companies and discourage them from locating offshore.^18,19,48,59 Some economists have recommended that foreign students who receive their PhDs for research in technical STEM-related fields at US universities should be encouraged to stay in the country to pursue their careers and receive automatic green cards enabling them to work in the United States.²⁰

But to remain competitive in synthetic biology, the US government will also need to take specific action on fundamental policy issues that will affect the field's development. One priority should be responding to and countering anti-GMO sentiments and legislation, which are on the rise. The ability to specifically modify, recode, transform, and manipulate the genetic code of organisms—and thus, the characteristics of the organisms themselves—is much more powerful using synthetic biology techniques than was ever possible before. In fact, synthetic biology has been described as “genetic engineering on steroids.”⁶⁰ It should thus be no surprise that long-standing debates, concerns, and activism surrounding the topic of GMOs would arise in response to synthetic biology. While the anti-GMO movement has been typically thought of as a European concern, which has diminished European agricultural competitiveness and has thus given the United States a competitive edge, there are warning signs that anti-GMO concerns are growing and will no longer be possible for scientists and policymakers in the United States to ignore. Simply put, concerns about GMOs that cannot be scientifically justified are at odds with US competitiveness in synthetic biology and other biotechnologies. The United States should actively counter anti-GMO policies, while also ensuring that synthetic biology is appropriately regulated, and work to inform the public about how products are regulated for safety.

The United States' approach to the regulation of biotechnology, different from that of Europe, has so far carried over to the regulation of synthetic biology applications. The focus of regulation and safety in the United States has traditionally been focused on the end result: the product. This is not to say that all conceivable GMO products are guaranteed to be safe, but it is the product that should be subject to a safety determination, not the process used to make it, whether that process is synthetic biology or another technique.

In contrast to the United States, European regulatory agencies have typically embraced the “precautionary principle,” which places the burden of proof on the developer of a product that the process used to make a particular product is not harmful. There are multiple formulations of the precautionary principle; one often-used definition came from the Wingspread Conference on the Precautionary Principle in 1998 and states:

When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically. … The process of applying the Precautionary Principle must be open, informed and democratic and must include potentially affected parties. It must also involve an examination of the full range of alternatives, including no action.⁶¹

While precaution in the face of indeterminate risks sounds to many a reasonable approach—it is the essence of the expression “look before you leap”—in practice, critics have charged that the usual result of its application is inaction.^62,63 In the case of synthetic biology, a precautionary approach would result in a general moratorium on the release and commercial use of synthetic biology until there is a research agenda, alternative approaches have been fully considered, a technology assessment has been performed, and there is national and perhaps international oversight for each of the technologies.⁶⁴ This could take many years even if all nations were in agreement about the need for it, which they are not.

The distrust of GMOs has had a detrimental economic effect in the EU. The prohibition on GMOs in the EU decreases profit margins for European farmers by up to a billion dollars each year.⁶⁵ The British government Biotechnology and Biological Sciences Research Council (BBRC) has charged that the precautionary approach has “effectively stifled GM crop farming in the EU.”⁶⁶ It costs £10-20 million more to put a GM crop through an EU approval process than for conventionally bred new crops.⁶⁷ A group of 21 prominent plant scientists wrote an open letter stating that Europe will lose research prominence unless field trials are allowed of GM crops and that they will fall short of producing “world-class science” unless a pro-science stance is taken by policymakers.⁶⁸ Science advisors to British Prime Minister David Cameron have called for scrapping “dysfunctional EU regulations” around GMOs, and they note the hypocrisy in that the EU imports 70% of its animal feed, most of it made with GMOs. The United States, Canada, Brazil, and Argentina grow 90% of the planet's GM crops.⁶⁹

It should be stated that the evidence on the safety of “GMO” foods is in, and the results are clear. Genetic engineering presents no unique hazards compared to other methods that create genetic modification, such as traditional breeding or hybridization. Major scientific organizations, including the American Association for the Advancement of Science (AAAS), the National Academies of Science, and the American Medical Association (AMA) all back GMOs as being safe. In a meta-review of the safety of genetically engineered crop research that evaluated 1,783 research papers and reports from the years 2002 to 2012, no significant hazards were identified.^70,71 The European Commission funded 1,340 research projects from 500 independent teams looking at GMO safety and none found risks.⁶⁹ In addition to the lack of harm found in GMO use, there are substantial benefits to using GMOs: lower food prices; less pesticide use, which is safer for farmers; less water needed; increased crop yields; and more stable prices.⁶⁹ There is also necessity: The UN FAO estimates that the world will need to grow 70% more food by 2050 just to keep up with population growth. There may be 10 billion people on earth, requiring more food to be grown in the next 75 years than has been produced in all of human history.⁷² Climate change, with the loss of arable land, will worsen this problem. Maximizing food production through GMOs may be the only avenue to provide people with enough food.

The anti-GMO movement has also cost lives. Vitamin A deficiencies cause more than 1 million deaths every year, as well as half a million cases of irreversible blindness.⁶⁹ In spite of this, the GMO Golden Rice, engineered to deliver more vitamin A than spinach, has not been allowed to be grown in India and the Philippines, largely due to the activities of Greenpeace and other anti-GMO organizations.⁷³ Kenya had an outright ban on GMOs in spite of an advancing crop disease that affects corn, the Maize Lethal Necrosis Disease, which could lead to food insecurity and famine as crops are destroyed by the virus.⁷⁴ Kenyan officials now say the ban resulted from their being misled by French activists who claimed that GM products cause tumors and were unfit for human consumption; the ban on GMOs is expected to be lifted by the end of 2015.^75,76

There is cause for concern that anti-GMO sentiments are increasing in the United States and will harm US competitiveness, particularly when it comes to realizing beneficial synthetic biology applications. In the United States, the use of anti-GMO sentiment as a marketing tool has been growing. Products that are marketed as not containing GMOs will account for 30% of US food and beverage sales by 2017.^77,78 Whole Foods started labeling their products that are GMO-free, stating that they were responding to their customers, “who have consistently asked us for GMO labeling and we are doing so by focusing on where we have control: in our own stores.”⁷⁹ By 2018, all products in their US and Canadian stores will be labeled to indicate if they contain GMOs. This is the first national grocery chain to set a deadline for “full GMO transparency.”⁷⁹ Chipotle and Trader Joe's also have decided to not sell foods made with GMOs and to use this fact in advertising campaigns. At least 20 states are considering GM labeling bills; most of those in favor of labeling would use those labels to avoid eating those foods.^69,72 Connecticut, Maine, and Vermont have already passed labeling laws.

Congress established the National Organic Standards Board (NOSB) under the USDA through the Organic Food Production Act, and it was charged with developing standards, which have become known as the “Organic Rule.” The Organic Rule expressly forbids the use of GMO crops, antibiotics, and synthetic nitrogen fertilizers, as well as food additives and ionizing radiation. The Organic Seal is a marketing tool and is separate from safety. But organic marketers represent conventionally grown or GM crops as dangerous.⁸⁰ Major scientific organizations have tended to be against labeling laws because of what happened in Europe: In 1997, when there was growing opposition to GMOs in Europe, the EU began to require labels. By 1999, to avoid the GMO labels, most European retailers had removed those ingredients, and now GM products cannot be found in European stores.⁷³

Anti-GMO groups have already found synthetic biology as a target. One example comes from Ecover, a Belgian company that makes detergents, and Method, which is a subsidiary company. Ecover purchased oils for its products developed by Solazyme, a US company that uses synthetic biology to produce an environmentally sustainable substitute for palm kernel oil in algae. Palm kernel oil is in high demand, which has led to conservationist concerns about overcultivation, deforestation, and loss of tropical habitats. Ecover found itself inundated with petitions to stop using synthetic biology for using what an anti-GMO group labeled an “extreme biotech oil.”⁸¹

Another example comes from the synthetic production of vanillin, the most dominant flavor compound in vanilla extract. Vanilla extract is made from vanilla beans, which are commonly harvested from Madagascar, the island of Réunion, Tahiti, and Mexico. Harvesting is an extremely labor-intensive process, as the vanilla plants need to be hand-pollinated for commercial quantities, and the result yields the world's second-most expensive spice, following saffron. The demand for vanilla flavoring cannot be satisfied by the harvesting and processing of vanilla beans alone; even now, most vanillin is made synthetically from petrochemicals and less commonly from chemically treated paper pulp. Evolva, a Swiss synthetic biology company developed a synthetic version produced using synthetic biology and has partnered with International Flavors & Fragrances (IFF-USA) to produce it. Vanillin does not taste as good as the vanilla extract that comes from vanilla beans, because the bean has more than 250 flavor and aroma compounds.⁸² But there are definite advantages to synthetic vanillin, in that synthetic production will not be affected by weather or crop failures, or the shifting costs of oil, thus resulting in a steady supply and less price volatility. Nonetheless, Evolva has also come under fire from anti-GMO activists for its use of synthetic biology. Friends of the Earth (FOE) “persuaded” Haagen-Dazs not to use vanillin made through synthetic biology, but since Haagen-Dazs uses only vanilla extract from vanilla beans, this was not likely to occur anyway. It is another example of the cynical use of anti-GMO sentiment for marketing purposes.^82,83

If anti-GMO sentiment increases, there will be a great deal of pressure placed on lawmakers by anti-GMO groups to adhere to the precautionary principle. Communicating the science behind GMOs is a much more difficult task than simply labeling it as bad, and the United States is not immune from applying a more precautionary stance to regulatory areas.⁸⁴ Still, resisting efforts to undermine a positive future for synthetic biology is critical for US competitiveness, as is making sure that synthetic biology products are, indeed, appropriately regulated. While the product, not the process, should be the focus of regulation and oversight, at this time there are gaps in regulation, and synthetic biology is likely to increase them.⁸⁵ As one example, a 2013 fundraising campaign on Kickstarter caused consternation by producing glowing plants and distributing seeds to more than 8,000 supporters.⁴⁴ The mechanisms used to produce the plants, distribute them, and plant them did not violate any current rules or regulations; however, allowing glowing plants to be introduced into the environment without regulatory review struck many as foolhardy and risked bringing about negative public opinions about synthetic biology.⁸⁰ Current oversight depends on whether plant pests or some plant pest component is used for engineering the plant. As many newer methods of genetic manipulation would not involve such a step, this would leave many engineered plants without regulatory review before they are cultivated in the environment for field trials or commercial production.⁸⁵

Encouragingly, this situation is likely to change for the better. In July 2015, the White House directed the 3 federal agencies that have oversight responsibilities for biotechnology products—the Environmental Protection Agency (EPA), the FDA, and the USDA—to develop a long-term strategy for the oversight of future products in biotechnology and to update what is known as the “Coordinated Framework.” The Coordinated Framework for the Regulation of Biotechnology was introduced in 1986 by the White House Office of Science and Technology Policy (OSTP) as a comprehensive federal regulatory policy to ensure the safety of biotechnology products beyond pharmaceuticals; it was last updated in 1992. Updating the framework became necessary, as it was outdated and confusing, and its complexity made it “difficult for the public to understand how the safety of biotechnology products is evaluated,” as the glowing plant example makes clear.⁵⁷ In addition, the regulatory process could be unnecessarily challenging for small companies. The Coordinated Framework will be updated and will clarify which agencies have responsibility to regulate products that might fall under authorities of multiple agencies.⁵⁷ In addition to this work, there will be a long-term strategy developed with an aim of making sure that the regulatory system is well-equipped to assess the risks associated with future biotechnology products. The National Academies of Sciences, Engineering, and Medicine have also been commissioned to perform an outside, independent analysis of the future landscape of biotechnology products.⁵⁷

Engaging in International Discussions

Formal mechanisms of international governance of synthetic biology need to be addressed by the US government. Synthetic biology has become a major topic in the Convention on Biological Diversity (CBD), which has 168 member nations but does not include the United States, which has signed but not ratified the treaty. The Cartagena Protocol in the CBD provides an international regulatory framework for the transfer, handling, and use of living modified organisms (LMOs) resulting from modern biotechnology. At the CBD 10th Conference in 2010, the members agreed that the release of products of synthetic biology requires caution and the application of the Precautionary Principle. Another protocol to the CBD, the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits, aims at sharing the benefits arising from the use of genetic resources in a fair and equitable way and will also affect the synthetic biology industry.

The US government should pay great attention to the activities of this treaty, to minimize the impact restrictions on developing synthetic biology technologies. Although the US is not bound by activities or resolutions of the convention, the synthetic biology market will be affected if the United States and the scientific community do not become more engaged in the CBD process.⁸⁶ The precautionary stance that the treaty parties are taking, as well as the possible consideration to bar some genetic sequences for use, may limit US synthetic biology exports and could hamper the field's development of beneficial applications.⁸⁷ The United States should work with other nations that are party to the Convention on Biological Diversity or the Nagoya Protocol to minimize the impact on US economic interests. At the heart of the treaty is a justifiable concern about the fair and equitable sharing of benefits arising from genetic resources. Rather than closing off a potentially broadly beneficial technology, other mechanisms should be created that directly address the need for fairness and access to benefits arising from the technologies.

Conclusion

Synthetic biology is a fast-moving field, and it has already been applied to the development of new vaccines and medical countermeasures as well as the production of biofuels, detergents, adhesives, perfumes, tires, and specialized chemicals that formerly required the use of petrochemicals. As the field continues to expand, synthetic biology may become a pervasive industrial technology. Proponents believe that synthetic biology and related technologies could be the foundation of a new manufacturing economy for the United States and could contribute to industries essential to US national security. While the field was pioneered in the United States, other nations are hoping that investments in this area will boost their economies, and so the great technical lead that the United States has enjoyed will inevitably shrink. However, it is imperative that the United States does not fall behind and makes investments to ensure that it is positioned to enjoy the fruits of a robust bioeconomy as well as participate in the technical back and forth that will set standards and limits for governance in controversial applications of the technologies. In actively taking steps to increase its global competitiveness in synthetic biology, the United States should also address fundamental policy issues about GMOs and make sure that all products are appropriately regulated—whether they are made through traditional methods, synthetic biology, or an innovative technology yet to be developed.

Acknowledgments

The author thanks Ken Bernard and Joel Kreps for their helpful comments on the manuscript, and the Alfred P. Sloan Foundation for research support.