Over the past year, torrents of tweets, rhetoric of “fire and fury,” and debates over “button” sizes have kept the world’s attention on the threats of nuclear weapons. After all, much of today’s adult population lived through the Cold War, an era when prospects of nuclear war veered dangerously close to reality. But despite the fears of an escalating nuclear confrontation, one of the most complex challenges emerging for American national security lies in a threat whose origins and propagation are more opaque: biotechnology.
In recent years, the H1N1 crisis, the Ebola epidemic, and various outbreaks of infectious diseases have all demonstrated the damage that biological threats can inflict. The 2001 Amerithrax case issued a powerful reminder that state and non-state actors alike can leverage biological agents toward malign ends. Today, a central issue within the biosecurity landscape involves “dual use research”—legitimate and well-intentioned scientific research with the potential to be used for harmful purposes.
For all the good biotech innovation is bringing to society, concerns about dual use research are increasing. In the wrong hands, technology that cures disease can also be destructive. This dilemma highlights the evolving effort—by the government, the public, and the scientific community—required to anticipate, preempt, and respond effectively to this threat. Yet balanced against the need for open academic inquiry and the life-saving potential of new technologies, broad categorical restrictions on research are infeasible and undesirable.
According to Nobel Prize-winning scientist Harold Varmus, who was appointed by President Clinton to serve as Director of the National Institutes of Health, new technologies like gene editing and genomic engineering “pose concerns and at least hypothetical dangers.” Now a professor at Weill Cornell Medicine, Varmus also told the HPR that recent controversies, such as those over the modification of influenza virus genomes, “require informed debate.”
It is more urgent than ever, therefore, that the scientific community hold candid conversations, establish clear and consistent norms and principles, and engage policymaking bodies—at home and internationally—to chart a productive path forward.
The Challenge of Duality
Today, rapid advances in biotechnology carry enormous promise. Innovation in the life sciences is reshaping environmental protection, transforming energy production, and revolutionizing the diagnosis and treatment of disease. Increasing globalization of scientific expertise has led to breakthroughs around the world and raised the quality of life in both developing and developed nations.
At the same time, “next-generation” advancement has been accompanied by increased risks, particularly in research focused on toxins and pathogens. Genetic engineering and synthetic biology have become more powerful, but also more dangerous, augmenting the virulence and transmissibility of pathogens. As a result, the threat of biological agents—either in the form of a natural pandemic outbreak or an intentional attack—has become an increasingly significant focus of national security and health policy.
Fortunately, deliberate attacks have been rare, at least in the United States. Since 2001, when two U.S. Senators and several members of the media received anthrax spores in the mail, the American public has not encountered an intentional biological attack. But with technical advances progressing rapidly and more widespread dissemination of research findings, some in the scientific community and national security establishment have raised new concerns.
In 2015, for example, a publication by the World Health Organization concluded that the variola virus, which causes smallpox, a disease that has been eradicated globally, could be recreated using synthetic biology. More shockingly, it reported that the process comprised a mere three steps, and could be completed by a skilled lab technician or undergraduate student in three months using genomes available in the public domain.
Given the apparent dangers, a hasty government response might attempt to curtail potentially dangerous research by imposing heavy limitations on permissible science. But such a response would disrupt America’s culture of academic inquiry and the free exchange of ideas, cornerstones of the scientific domain for centuries. The United States has established itself as a world leader in biomedical research in large part thanks to its transparent scientific enterprise. As Varmus explained, “Historically we have benefited from policies that favor openness in research.” Balancing the need to mitigate risks without impinging on biomedical research is the challenge that makes any simple solution elusive.
An Old Threat? Asilomar and Recombinant DNA
The tension between biotechnology and biosecurity is nothing new. In the early 1970s, scientists discovered how to combine different genes into new combinations to produce engineered proteins in bacteria. This technique, known as “recombinant DNA,” offered clear therapeutic applications. In 1975, however, a number of scientists led by Stanford biochemist Paul Berg called for a moratorium on recombinant DNA, citing the uncertainty of its risks. They convened an international conference of biologists, lawyers, journalists, and policymakers, assessed risks and benefits, and ultimately established detailed guidelines governing future research. It was at this Asilomar Conference that they agreed it was important for research to continue, but only under specific guidelines.
These guidelines provided the groundwork for subsequent regulations and laws in the United States and worldwide. In the years since, they proved to be both useful and effective. Worldwide use of recombinant technology blossomed, ushering discussions of biomedical research into public discourse and driving the expansion of the biotech industry.
Today, products of recombinant DNA technology exist in virtually every pharmacy and hospital in the developed world. They include life-saving hormones such as insulin and erythropoietin, which patients with diabetes and anemia require to survive, vaccines like those for hepatitis B and HPV, and diagnostics such as those that detect the presence of HIV.
Since Asilomar’s discovery in 1975, “none of the bad outcomes worried about at the time [have] materialized,” said Matthew Meselson, a Harvard geneticist best known for his landmark discovery of how DNA replicates. “On the contrary, recombinant DNA technology has made possible many benefits in medicine, in agriculture and in other fields, including basic understanding of life processes.” Meselson, whose work as a consultant for the U.S. government on bioweapons with Henry Kissinger under the Nixon Administration led to the first ban on biological weapons, added, “The evidence of nearly half a century of history is that the solutions proposed then were adequate, perhaps more than adequate, and that fears were exaggerated.”
Modern Capabilities: Second-Generation Biotechnology
Today, things have changed. In the last months of Barack Obama’s presidency, his Council of Advisors on Science and Technology sent him a letter raising concerns about “second-generation methods” in biotechnology. According to the report, the “first-generation” technologies of recombinant DNA, while powerful, faced significant limitations in regulating gene expression, targeting genes with specificity, and delivering DNA into a cell. In contrast, newer “second-generation” methods enable precise gene delivery, high-throughput DNA synthesis, and direct gene editing.
Modern methods enable scientists to assemble recombinant genes more quickly than ever before, allowing scientists to manipulate viruses and pathogens with greater ease. New techniques have also enhanced the potential to weaponize naturally occurring pathogens by engineering them to overcome existing immunity and become drug resistant. A team in Australia demonstrated, for example, that by inserting one gene into the mousepox genome, the new virus became capable of killing mice that had previously been resistant.
To be sure, creating sophisticated tools of bioterror is still no simple task. Moreover, the probability of an ill-intentioned individual acquiring the technical competence and resources is still fairly low. “The most dangerous near-term threat by far is certainly from nature,” argues Meselson. “As for deliberately caused disease, history is again relevant. It is now 16-plus years since the anthrax letter attacks. What can be learned from this? First, that there has been no repetition. Even though it is relatively simple to prepare dispersible anthrax spores, even though the letter attacks of 2001 showed that simply mailing the spores through the post works, there has been no repetition.” But Meselson acknowledges that risks exist. And in an increasingly digital and interconnected world, the threat is still real.
Dual Use Research of Concern
Potentially dangerous biological research is difficult to regulate precisely because it is “dual use.” In an overwhelming majority of cases, it is conducted legitimately for medical or academic aims. And while nuclear programs require large laboratories and facilities, bioengineering requires comparatively little lab space and modest resources, making detection, let alone regulation, difficult.
In the United States, current policies surrounding “dual use research of concern” apply specifically to 15 agents and toxins and seven types of experiments. But these policies have flaws. Perhaps the biggest complication is that research may seem not to possess any “dual use” potential in its initial stages, only for concerns to emerge as it progresses. Furthermore, the policies only apply to federally funded research and institutions—privately funded institutions are omitted, as are pharmaceutical and biotech companies. And although these policies withdraw government funding in the case of non-compliance, they do not actively impose sanctions. On another level, issues of dissemination persist. While large academic institutions and research facilities may adhere closely to policies, no universal standards for scientific journals exist, and no norms in international settings have been established.
Charting A Way Forward?
Is there, then, a clear way forward? Left with no easy options, one solution is to impose stringent bans, to prohibit experiments, or to sanction non-compliant journals. Governments could also restrict access to sensitive knowledge to only individuals with security clearances. These broad, categorical answers are likely poor solutions, since they are, as President Obama’s Council of Advisors on Science and Technology reported, “likely to interfere with fulfilling the promise of biotechnology for improving human health and welfare.” Indeed, the enormous public good ushered in by the age of recombinant DNA, when contrasted with previous setbacks in biomedical research after heavy-handed restrictions such as the ban on federal funding for human embryonic stem cell research, warns us of the risks of generalized solutions and indiscriminate regulations. Moreover, these measures may not even prove effective, since scientific expertise is too widely disseminated across nations.
Perhaps despite the changes in technology, the principles that were successful at Asilomar can still be applied with success today. International forums for scientists, open dialogue among policymakers, private-sector engagement, and participation from educational institutions will be critical if we hope to bolster research and biosecurity. Diagnosis must precede prescription, if scientists seek to develop solutions with nuanced thought rather than rushed and imposed politicization.
Certainly, greater discussion and awareness will be needed. “Inclusion of [dual-use research] in graduate training programs and greater attention to it by groups like the Nuclear Threat Initiative could help with these matters,” said Varmus. In addition to the scientific community, policymakers in the government can play important roles as well. As John Holdren, former science advisor to President Obama and Director of the Office of Science and Technology Policy, told the HPR, “I believe the policies we worked out in the Obama Administration, after wide consultation and careful thought, strike the right balance.” Holdren added that “increased cooperation in intelligence and biosurveillance is one way to work with allies internationally to manage biosecurity risks.”
Perhaps the most effective strategy the government can implement involves response and preparedness. Multiple public health crises in recent years have underscored the importance of efficient interagency protocols, response coordination, and emergency planning. As Meselson explained, “In the case of smallpox or Ebola, for example, or some newly emerging virus, the toll can be greatly reduced by traditional public health measures—keep children home from school, cancel big spectator sports events, curtail travel, measures of personal hygiene, etc. The great degree to which such measures can be effective is often unappreciated.”
In the end, scientists, policymakers, and citizens should continue to have robust conversations and thoughtful dialogue. As inevitable as it is that biotechnology will continue to advance, it is equally certain that new risks will continue to emerge. Only balanced and informed foresight, guided by lessons of history, will ensure that our policies are smart and effective. Most importantly, we should recognize that scientific advancement is not without mistake, and that difficult corrections will inevitably be needed. We would do well to remember that the price of science, an imperfect human art, is humility from us all.
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