How genetic editing became a national security threat
25 April 2016
http://thebulletin.org/how-
Director of National Intelligence James R. Clapper sent shock waves through the national security and biotechnology communities with his assertion, in his Worldwide Threat Assessment testimony to the Senate Armed Services Committee in February, that genome editing had become a global danger. He went so far as to include it in the report’s weapons of mass destruction section, alongside threats from North Korea, China’s nuclear modernization, and chemical weapons in Syria and Iraq. The new technology, he said, could open the door to “potentially harmful biological agents or products,” with “far-reaching economic and national security implications.”
So what has warranted this warning, and what can be done to mitigate the threat?
Since the discovery of the double helix in 1953, biotechnology has made progress exceeding that of arguably any other technology in human history. Genome editing is not a new process; it was the subject of the 1975 Asilomar Conference, convened to establish standards that would allow geneticists to conduct cutting-edge research without endangering public health. Since then, advances like the polymerase chain reaction process, the human genome project, and the Encyclopedia of DNA Elements project have fueled our understanding of the human genome, accelerated through advances in computing power, data storage, and big data algorithm development. Landmark results include the first synthesis of a virus in 2002 and the first synthetic cell in 2010. Now along comes clustered regularly-interspaced short palindromic repeats—Crispr for short—which is changing everything.
Other editing techniques have been around for more than a decade but they are laborious, less accurate, and quite expensive. Before that, previous traditional methods required generations to see results. While some techniques can recognize longer DNA sequences and have better specificity than Crispr, they are costly ($5,000 for each order versus $30 for Crispr) and difficult to engineer, sometimes requiring several tries to identify a sequence that works. Hence the rise of Crispr, which, along with Crispr associated proteins (Cas), provides a precise way to target, snip, and insert exact pieces of a genome. (The Crispr-Cas9 protein has received the most attention in this recent discussion, yet other enzymatic proteins such as the Crispr-Cpf1 use a different type of “scissors” and might be just as effective.)
The benefits of such technology are obvious. Because preferred traits can rapidly enter a species, test animals like mice can be designed more efficiently for biomedical experiments, mosquitoes can be engineered so they cannot reproduce (and therefore cannot spread malaria), plants can be developed for drought resistance and higher yields, and diseases can be eliminated by deactivating the responsible genes in a given host. The bioengineer and author Robert Carlson notes that genome editing shows great promise for next-generation plastics, agricultural products, bioremediation organisms, carbon-neutral fuels, novel enzymes, and better vaccines.
So where’s the threat? For starters, the low cost and growing availability of these powerful new techniques means untrained personnel will inevitably gain access to them, and lack of experience, disregard for codes of ethics, and ignorance of appropriate precautions all but guarantee dangerous outcomes. The dual-use nature of gene editing also falls under broader concerns about do-it-yourself biology, biohacking, neighborhood labs, and related trends. And even in experienced hands, this new technology holds the potential for permanently and irreversibly altering the human genome without knowing what the full results might be. Subtle changes, for example, intended to affect only genetic diseases, could have unknown consequences, interfering with signaling pathways, altering immune responses, or even threatening the species itself.
These same concerns hold for other species as well. One study in mice found that mismatched nuclear and mitochondrial DNA led to mice that became exhausted more quickly and had different learning speeds. Furthermore, such changes have the potential for altering entire ecosystems. Creating a mosquito that could not reproduce might stop the spread of a disease but it would also eliminate a food supply for other animals. What other species might be affected in such an altered ecosystem?
There is also the question of accidents and negligence. Will experiments be conducted with proper biosafety and biosecurity procedures in mind? What if an altered organism escapes into the wild? Will all those conducting these experiments understand that certain tests are simply too dangerous to undertake?
And what about weaponization? Pathogens engineered for biological attacks could target individuals or groups; they could also be employed in large-scale attacks with devastating consequences. Additionally, they could be developed to strike the plants or animals that sustain our food supplies.
Gene editing techniques could produce forms of diseases that barely resemble their naturally occurring counterparts. Such engineered pathogens could sicken or even kill hundreds of thousands of people.
Armed with the proper genetic sequences, states or bioterrorists could employ genome editing to create highly virulent pathogens for use in such attacks. They could, for example, change a less dangerous, non-pathogenic strain of anthrax into a highly virulent form by altering the genome, or recreate pathogens such as the deadly smallpox virus, which was eradicated in the wild in 1980. Or they could develop specific weapons that target either individuals or even entire races: With the right manipulations, a pathogen could be made to have greater invasiveness or virulence in a target population.
As the technology continues to proliferate, this list of threats is likely to grow. With advances such as Crispr-Cas9, genome editing has already advanced from an art and a science to an industrial and engineering process. The limits today are a matter of scale and our incomplete understanding of host response to these genome manipulations. As research goes ahead, we should expect those limits to break down and the technology to become more widely available, more effective, less costly, and above all increasingly capable of more complex manipulations.
Mitigating the dangers. Trying to put this genome genie back in the bottle would be self-defeating and would fail in the long run. The technology has already been widely shared and the excitement surrounding its possibilities is far too great.
However, democratization will result in more access to this technology by individuals and groups that may lack proper training, do not have proper containment facilities, and are not subject to regulations and ethics. Such actors will also not have the traditional oversight and institutional structure designed to ensure proper use of the technology for legitimate science and not for rogue or unguided and unsupervised experiments. No Institutional Biosafety Committees will govern the work at many of these labs or do-it-yourself facilities. And they will certainly not be encumbered by the Dual-Use Research of Concern (DURC) policy, which only pertains to research funded by the US federal government. Hence the dangerous proliferation window at the core of James Clapper’s testimony.
In biotechnology, new laws and regulations have typically come after scientific advances outstrip existing rules. For example, it took dangerous gain-of-function experiments with influenza transmissibility to spur the Obama administration to develop its DURC policy for institutional oversight. This policy now governs government-sponsored research on 15 particular agents and toxins and seven categories of experiments, with the hope of guarding against developments that enhance the susceptibility of host populations or increase the transmissibility of pathogens.
Still, much can and should be done at all levels to address the potential threat posed by genome editing.International laws and treaties, including UN Security Council Resolution 1540, which governs the proliferation of WMD, should be strengthened to reflect the danger posed by unregulated gene editing. The Biological Weapons Convention should continue to emphasize the importance of national laws, policies, and regulations, with a particular eye on the dangers of misusing synthetic biology. Global biosurveillance and forensics programs should be strengthened to look for evidence of abuse. The DURC policy should be pushed down to smaller labs, individuals, and even those commercial entities that might be promoting gene editing capabilities as measures thatshould be responsibly implemented for the good of society. Authorities should continue to strengthen biorisk management, which considers biosafety, biosecurity, and bioethics around the globe. And perhaps it is even now time to convene a follow-on Asilomar conference to consider the implications of this powerful new biotechnology.
Above all, the inclusion of genome editing as a worldwide mass threat should serve as an important wake-up call.The proliferation of this technology now and in the future has the potential to dramatically alter human existence, in good ways as well as bad. If we marshal it properly, it could lead to improvements in the quality of life for peoples across the world. If we don’t, it could imperil life itself.
