Balancing Act: Precision Medicine and National Security

ABSTRACT

Developments in genetics, pharmacology, biomarker identification, imaging, and interventional biotechnology are enabling medicine to become increasingly more precise in “personalized” approaches to assessing and treating individual patients. Here we describe current scientific and technological developments in precision medicine and elucidate the dual-use risks of employing these tools and capabilities to exert disruptive influence upon human health, economics, social structure, military capabilities, and global dimensions of power. We advocate continued enterprise toward more completely addressing nuances in the ethical systems and approaches that can—and should—be implemented (and communicated) to more effectively inform policy to guide and govern the biosecurity and use of current and emerging bioscience and technology on the rapidly shifting global stage.

WHAT IS PRECISION MEDICINE?

With developments in genetics, pharmacology, biomarker identification, and imaging, medicine is increasingly focused on developing and articulating therapeutics that are based—and act—upon individuals’ unique genotypic and/or phenotypic characteristics that contribute to healthy function or as affected by specific pathologies. Arguably, any apt execution of medicine should be “personalized” to meet the particular needs of individual patients, but advances in biosciences and technology have enabled increasingly precise approaches in this regard. The past decade has evidenced major advances in innovative biotechnological tools, such as CRISPR and other gene-editing techniques that are making the ability to study and manipulate molecular biological substrates of health and disease more facile. Animal models of genetic disease, which were time- and labor-intensive (e.g., to backcross and develop gene lineages), can now be developed in weeks, which, together with bioengineered test bed tissue models, enable rapid throughput screening of various therapeutics. At the apex of this biotechnological wave are advances in human genomic sequencing, which formerly was an expensive, arduously monthslong process, but can now be performed in hours, for costs that are often less than $1,000 (for commercially available test kits).

The U.S. national research infrastructure—comprised of public and private efforts—has been aligning with a precision medicine direction apace with the availability of these technological tools. Public, for-profit companies (e.g., 23&Me and Ancestry.com) provide direct-to-consumer genome analysis kits for prices lower than their cost. When coupled to clinically derived medical information, such genomic data, in aggregate, become commodities of interest to the pharmaceutical and biotechnology industries. Herein lies the true profit: The sale of aggregate data to interested companies and other entities. Often, the consumer is unaware that their medical data are being leveraged in these ways. And, while federally supported efforts, such as the NIH “All of Us” initiative,¹ are fully voluntary and patients are encouraged to participate as part of a recognized biomedical research effort, and federal mandates such as the Genetic Information Nondiscrimination Act afford protection against (primarily occupational) bias and mistreatment based upon genotypic information and its inference(s), such safeguards may be insufficient. The “All of Us” initiative is poised to collect over a million genomes and their associated expressions (i.e., phenotypes), toward advancing the discovery of precision medical (and socio-environmental) interventions. The DoD is similarly amassing a large cohort of Air Force personnel in order to acquire extensive biomedical and genomic data.²

Expression data (i.e., the proteins and other expression molecules for which genes are responsible) is important to health and medicine because not all genes are expressed all the time, and many genes respond to physiological, environmental, and/or pharmacological factors. Simply, the genes responsible for particular diseases can either be activated and active, or can be nonexpressed, and this expressive failure can lead to omission phenotypic components that (1) can directly lead to the expression of a pathological state and/or (2) are important in suppressing disease, and thereby increase susceptibility and vulnerability to pathology. Situational awareness of genetic factors and phenotypic expression status provides roadmaps to manipulate variables (ranging from the cellular to the socio-environmental) to affect health and disease on individual bases.

We view approaches to the use of these individual data as falling into two general categories: the first we consider to be “passive” precision medicine, which entails the use of drugs, diet, exercise, or other interventions that are based upon an individual’s genetics and the second we view as “active” precision medicine, which involves the use of drugs, genetic manipulators, or other advanced biotechnologies to directly target particular genes to regulate their expression or to potentially mitigate disease and/or alter physiology (and evoke effects in a variety of systems, inclusive of ways that that can modify cognition, behavior, performance, or other human attributes).

A Two-Sided Blade: The Risks of Precision Biomedicine

To be sure, precision medicine offers considerable promise for the treatment of disease and preventive care. But the capabilities afforded through precision biomedical tools and methods also incur risk and threats to biosecurity. For example, data utilized to drive precision medical approaches (i.e., genomic, genetic, and phenotypic information) may be viable for—and vulnerable to—usurpation in order to (1) manipulate/corrupt these data directly and/or (2) obtain information necessary to develop “precision pathologies” based upon individual or group sensitivities and susceptibilities. Such information, which we have called “biodata,”³ was at first only regarded as a privacy risk, which would seemingly be mitigated by the Genetic Information Nondiscrimination Act (although other forms of data might necessitate more encompassing legislative protection). However, emerging technological tools and new methods have expanded the capability to harness such means to evoke a broader range of effects that could exert disruptive and/or destructive influence upon human health, economics, social structure, military capabilities, and global dimensions of power.^4–6

Current international competitors and adversaries have already recognized the value of such data as a path to hegemony in biomedical markets and have demonstrated willingness to employ such data in interest of military capabilities.^7–9 In many ways, capabilities for acquiring and processing genomic data have advanced so rapidly as to be apace with the almost linear progress that characterized the early days of cyber technologies. To wit, there is ongoing consideration that much data are already “out of the box” and available for—if not in—use in ways that threaten U.S. economic, public health, and overall national security. Even if this is so, U.S. biocybersecurity vulnerability is not a fait accompli. To be sure, the United States is making strides in designating biodata as critical infrastructure in support of its growing bioeconomy.¹⁰ Thus, data generated by, and relevant to, military and intelligence force capabilities of the United States and its allies must be subject to the most rigorous cybersecurity oversight and control, lest such information be purloined for the aforementioned uses by current competitors and potential hostiles.^3,11 Additionally, malicious uses of biodata, and their applications in molecular bioscience and technology (gene-edited, modified, or novel agents), are not currently well-addressed by the scope and tenor of the extant Biological Weapons Convention; we have called for revisiting, if not revising the convention to better align with and address ongoing developments in the field.^12,13

For example, the development and use of what we term “precision maladies” could be articulated as passive (i.e., indirect) or active (i.e., or direct) operations. If indirectly, knowledge of military and intelligence personnel biomedical information enables competitors and adversaries to identify specific individuals and/or groups of individuals. Despite methods employed to protect identities, it has been shown that anonymized data can be analyzed to enable individual identification based on portions of (their—or familial) DNA.¹⁴ Clearly this represents a risk for covert operations. As well, the convergent application of decision technologies, machine learning, and artificial intelligence with biotechnology is being considered for use in influence and disruptive operations.^15–18

Direct genetic targeting of individuals or groups is also a growing area of concern. As the ability to modify existing agents and/or create agents anew for weaponized use continues to advance, the capabilities and value of extant means of deterrence will concomitantly erode (e.g., the use of CRISPR-based gene-editing techniques to bypass current safeguards in bio/microbial weapon development and use).¹⁹ These risks and levels of mitigation are noted in Figure 1.

FIGURE 1.

Proposed framework of risks associated with biomedical advances in military contexts, and loci at which mitigations or prevention(s) should be engaged.

The figure illustrates the framework of risks associated with precision medicine in the military context and where mitigations should be applied. The whole of “biodata” collected from the military has two broad risk categories: direct misuse and indirect misuse. Direct misuse can include harms from bioagents developed to specifically target warfighters based on their biodata elements. Indirect misuse can include harms arising from privacy violations or targeting warfighters en masse through environmental exposures or other means. We recommend a three-tiered approach; at the macro level, military biodata must have adequate protections; risk assessments must then be performed for both direct and indirect misuse possibilities; and finally, dedicated countermeasures could be developed for specific threats or harms.

Of note, the United States has participated in robust international discourse and deliberations focal to the use and/or potential misuse of genomic information, as relevant to the convention on Biological Diversity and the Nagoya Protocol—discussions which largely center upon establishing approaches to balancing multinational genomic data sharing and direct economic benefit sharing. But these discourses do not address the broader issues we have defined here, which we believe require more extensive international forums for address and resolution. Toward such ends, we recommend that the science and technology components of the NATO alliance be engaged in review and guidance of military uses of precision medical data, working not as a singular entity, but in concert with other international scientific societies that are devoted to ethically sound global advancement of precision medicine.

CONCLUSIONS

As developments and capabilities in precision biomedicine advance, and the U.S. military pursues its benefits, we urge that military biodata be regarded and treated as critical operational information. In this light, we recommend that all such data be subject to rigorous digital biosecurity oversight and controls. Further, we recommend a full “biodata risk analysis” to assess the viability of compiled or portioned biodata to be (mis)used to incur disruptive and/or destructive influence and effect(s) upon the military and U.S. national security and public safety at-large. In addition, we recommend that full consideration and address of all ethico-legal (and social) implications and issues incurred by the use of biodata and precision biomedical approaches within the military. The current efforts of the human performance research group are optimistic in this regard; however, continued enterprise is needed to more completely address more nuanced issues of ethical systems and approaches to be employed, and how such endeavors can and should be implemented (and communicated) both within public fora, and upon the rapidly shifting global stage.^20–23 With the early employment of such measures, a preventative stance is afforded which will hopefully mitigate downstream harms, but in preparedness for such events, remedies to “precision maladies” should also be researched and created.

CONFLICT OF INTEREST STATEMENT

None declared.