Genetic Frontiers
Unraveling the Impact and Anticipating Future Challenges of SYNBIO
By Dr. Julie A. Preston, Captain Mithun P. Sheth, and Staff Sergeant Jonathan S. Sayles
Article published on: June 1, 2024 in the Army Chemical Review 2024 Annual Issue
Read Time: < 10 mins
In the evolving technological era of large-scale combat operations and multidomain operations, the U.S. Army is
facing a most complex problem of simultaneously meeting and overmatching its competitors and enemies across
multiple domains of warfare. Adding to this challenge, the People’s Republic of China declared biology to
be “a new domain of war” and announced plans to make China the global leader in technologies like
genetic engineering. 1
Advances in synthetic biotechnology, including gene-editing technologies such as clustered regularly interspaced
short palindromic repeats (CRISPR), promise protection— and even cures—from diseases, but they also
create new security risks. Research scientists can use CRISPR technology to selectively modify an
organism’s deoxyribonucleic acid (DNA) by incorporating foreign DNA into a living host cell. Five years
ago, a Chinese scientist used CRISPR technology to create the first gene-edited babies, for which he faced
international accusations of violating medical ethics. While this technology can potentially be used to cure
genetic diseases, it also has the potential to edit bacterial or viral genomes to create enhanced pathogens. The
2022 “National Biodefense Strategy and Implementation Plan for Countering Biological Threats, Enhancing
Pandemic Preparedness, and Achieving Global Health Security”
2 categorizes biological threats among the most severe threats to the United
States and calls for bold approaches to transforming the Nation’s biodefense program.
Due to the increasing ubiquity and simplicity of synthetic technologies, the chemical, biological, radiological,
and nuclear (CBRN) profession and enterprise must be prepared to encounter its use on future battlefields.
Raising awareness of this technology should begin in the classroom through modernization of the biodefense
program of instruction to include information on synthetic biology (SYNBIO).
SYNBIO is a multidisciplinary field that is centered on creating and modifying organisms and their genetic
material to produce novel phenotypic traits previously unseen in their natural predecessors. Advances in the
field have allowed humankind to modify pathogens for desired functionality, resurrect eradicated viruses, and
synthesize novel pathogens. Due to the technological advancement rate and the scope of application, SYNBIO poses
a significant threat to national security. Advances in SYNBIO have created tools that could enable a state,
group, or individual to produce novel viruses that are intentionally or unintentionally capable of impacting
large groups of people. 3 Weapons
resulting from SYNBIO would enable state actors to have a serious effect on an area—specifically, on the
people, plants, and livestock in the area—while leaving critical infrastructure primarily untouched. For
example, in 2002, scientists at Stony Brook University, New York, used SYNBIO to construct a live polio virus
from genetic information publicly available on the Internet. 4 Using SYNBIO, scientists can also modify existing organisms so that they
possess abilities they would not naturally exhibit, allowing potential adversaries to develop new or enhanced
agents. 5 CRISPR is but one of
several types of gene-editing technologies that allows for exact genome edits; it is so efficient and
cost-effective that it has significantly increased the threat of SYNBIO to national security.
CRISPER is the most-discussed gene-editing technology during national and international security debates 6 because it does not require
sophisticated knowledge, specialized equipment, or the time that was needed for earlier gene-editing
technologies. 7 CRISPR uses a
guide ribonucleic acid (RNA) strand to locate a desired target gene in the DNA, where enzymes cause a break in
the double-stranded DNA, allowing the gene to be modified. 8 In short, scientists can cut and paste segments of DNA at desired
locations within the genome. With CRISPR, any double-stranded DNA sequence in human cells and pathogenic
invaders can theoretically be targeted. This allows for the technology to be used for beneficial purposes; and
in December 2023, the U.S. Food and Drug Administration approved the first-ever gene-editing therapy for humans.
CRISPR can now be used to treat sickle cell disease, a blood disorder caused by a single gene mutation. 9 However, gene-editing technology
can also be used for nefarious purposes—and CRISPR accessibility, affordability, and efficiency make it an
attractive vehicle for biowarfare. Furthermore, CRISPR efficiency increases when paired with artificial
intelligence, which can make use of machine learning to predict the effect of specific gene editing on an
organism, avoiding time-consuming laboratory experiments and testing cycles. 10
Because gene editing allows scientists to edit and shape whole genomes of bacteria and viruses with new
properties, 11 concerns about
its possible future use have been raised. U.S. scientists who were researching CRISPR modified the mousepox
virus by inserting a gene for a natural immunosuppressant, originally intending to increase antibody production;
instead, it turned off the part of the immune system that usually fights the virus, creating a more deadly form
of mousepox. 12 These
experiments suggest that it is possible to produce a smallpox variant that is resistant to the vaccines that are
such an integral part of any deterrence strategy since vaccines reduce the incentive for adversaries to release
certain agents by rendering attacks unsuccessful. 13
CRISPR might also be used to edit genes of entire populations of disease-spreading animals, like mice and
mosquitoes. 14 Researchers have
attempted to modify the DNA of these animals so that future generations cannot spread disease. That objective is
dangerously close to modification of their DNA so that future generations can more efficiently and effectively
spread disease.
The implications of future use of these scientific advancements should be considered in terms of their
significance to international security with regard to proliferation, deterrence, and unconventional weapon
development. Several nations have engaged in covert biological weapons programs in the past, 15 and many nations openly
conduct research that would be illegal in the United States. In the People’s Republic of China, He Jiankui
used CRISPR to edit genes in a human embryo in an attempt to create a baby that was immune to the human
immunodeficiency virus (HIV); this sparked fears that he had opened the door to further embryo modification,
such as the creation of “designer babies,” for which parents could leverage gene-editing technology
to select traits they value for their offspring. 16 Chinese scientists also used CRISPR to remove genes that inhibit muscle
and hair growth in goats, successfully increasing yields of meat and wool. 17 Geneticist Denis Rebrikov, of the Pirogov
Russian National Research Medical University, Moscow, Russia, plans to use CRISPR to genetically modify embryos
to treat inherited deafness. 18
His research has been widely condemned as unethical, as these germline edits can be passed to future offspring.
Despite the backlash, Rebrikov is still seeking approval to move forward.
Although China permits germline gene editing for research purposes, edited human embryos are not allowed to be
used to establish a pregnancy. He Jiankui, therefore, spent 3 years in a Chinese prison for his embryo
modifications that resulted in twin girls, but he has since been released. He is again working with
CRISPR—this time in an attempt to cure Duchenne muscular dystrophy, a hereditary degenerative disease of
the muscles. There are lingering concerns among experts about his motives as well as the motives of the Chinese
government in allowing him to continue his research in the field.
19
In addition to state-sponsored laboratories with the technology necessary to reengineer existing organisms or
genomes for defined purposes, the affordability and accessibility of SYNBIO technology allows anyone with the
right equipment and a crude laboratory to create a vaccine-resistant virus or make existing bacteria more
dangerous. 20 They could even
resurrect an eradicated virus, perhaps by turning the easily obtained cowpox virus into smallpox. 21 Because these gene-edited
pathogens are unfamiliar, manifestations of these biothreats are unpredictable, creating additional monitoring
and detection challenges. 22
To further complicate matters, no international legal, ethical, or moral framework for determining a common
understanding of the safe use of SYNBIO exists. Likewise, there is no international oversight committee for gene
editing and no agreement- on the ethical boundaries within which CRISPR may be used. 23 The Oviedo Convention on Human Rights and
Biomedicine is the only legally binding international protocol that addresses gene editing; Article 13 of the
Oviedo Convention allows gene editing for prevention, diagnosis, or treatment—but only if there is no
modification in descendants’ genes. 24 It prohibits the type of germline modifications that scientists in
China and Russia are attempting to conduct. The Oviedo Convention, was not signed by the United States, China,
or Russia.
With new technology comes the genuine possibility of new and more sophisticated threats. The field of SYNBIO has
been expanding the possibilities of biowarfare for several decades, and recent advances in biotechnology are
making it even easier to develop and use biological weapons. With the advent of more-straightforward, cheaper,
and more-accessible gene-editing technology like CRISPR, the danger has become more urgent. This will
undoubtably expand the scope and diversity of the biological threat landscape. In order to help the Department
of Defense (DoD) achieve and maintain its biodefense goals, our defense capabilities must evolve alongside these
changes. The 2023 Biodefense Posture Review 25 calls for the modernization of operations to sustain readiness and
resilience against burgeoning threats. We must implement the plan outlined in the National Biodefense
Strategy by pursuing innovative approaches, encouraging learning, and linking stakeholders with new
tools and ideas, 26 starting with our student Soldiers at the U.S. Army Chemical, Biological,
Radiological, and Nuclear School (USACBRNS), Fort Leonard Wood, Missouri. When a CBRN Soldier understands that
there may be altered or combined biological threats, then he or she realizes the limitations that can be imposed
by traditional knowledge of diseases and, thus, can provide more flexible and dynamic recommendations to ground
force commanders.
Endnotes
1. 2023 Biodefense Posture Review, DoD, 2023, https://media.defense.gov/2023/Aug/17/2003282337/-1/1/1/2023_BIODEFENSE_POSTURE_REVIEW.pdf,
accessed on 28 March 2024.
2. “National Biodefense Strategy and Implementation
Plan for Countering Biological Threats, Enhancing Pandemic Preparedness, and Achieving Global Health
Security,” The White House, U.S. Government, 2022, https://www.whitehouse.gov/wp-content/uploads/2022/10/National-Biodefense-Strategy-and-Implementation-Plan-Final.pdf,
accessed on 28 March 2024.
3. Jason Matheny, “RAND President and CEO Presenting
to House Permanent Select Committee on Intelligence,” RAND Corporation, 28 February 2023, https://www.rand.org/pubs/articles/2023/rand-president-and-ceo-presenting-to-house-permanent-select-committee.html,
accessed on 28 March 2024.
4. Andrew Pollack, “Traces of Terror: The Science;
Scientists Create a Live Polio Virus,” New York Times, 12 July 2002, https://www.nytimes.com/2002/07/12/us/traces-of-terror-the-science-scientists-create-a-live-polio-virus.html,
accessed on 28 March 2024.
5. 2023 Biodefense Posture Review.
6. Margaret E. Kosal, “Emerging Life Sciences and
Possible Threats to International Security,” Orbis, 2020, pp. 599–614, https://doi.org/10.1016/j.orbis.2020.08.008, accessed on 28 March 2024.
7. Arthur L. Caplan et al., “No Time to
Waste—The Ethical Challenges Created by CRISPR: CRISPR/Cas, Being an Efficient, Simple, and Cheap
Technology to Edit the Genome of Any Organism, Raises Many Ethical and Regulatory Issues Beyond the Use to
Manipulate Human Germ Line Cells,” EMBO Press, 2015, pp. 1421–1426, https://doi.org/10.15252/embr.201541337, accessed on 28 March 2024.
8. Melody Redman et al., “What is CRISPR/Cas9?,”
BMJ Journals: ADC Education & Practice Edition, 2016, pp. 213–215, https://doi.org/10.1136/archdischild-2016-310459, accessed on 28 March 2024.
9. Gina Kolata, “FDA Approves Sickle Cell Treatments,
Including One That Uses CRISPR,” New York Times, 8 December 2023, https://www.nytimes.com/2023/12/08/health/fda-sickle-cell-crispr.html, accessed on
28 March 2024.
10. “Science & Tech Spotlight: Synthetic
Biology,” U.S. Government Accountability Office, 17 April 2023, https://www.gao.gov/products/gao-23-106648, accessed on 28 March 2024.
11. Caplan et al.
12. Debora Mackenzie, “U.S. Develops Lethal New
Viruses,” New Scientist, 9 October 2003, https://www.newscientist.com/article/dn4318-us-develops-lethal-new-viruses/,
accessed on 29 March 2024.
13. Kosal.
14. Mark Shwartz, “Target, Delete, Repair: CRISPR is
a Revolutionary Gene-Editing Tool, But It’s Not Without Risk,” Stanford Medicine
Magazine, 26 February 2018, https://stanmed.stanford.edu/crispr-for-gene-editing-is-revolutionary-but-it-comes-with-risks/,
accessed on 29 March 2024.
15. 2023 Biodefense Posture Review.
16. John Ruwitch, “His Baby Gene Editing Shocked
Ethicists. Now He’s in the Lab Again,” National Public Radio, 8 June 2023, https://www.npr.org/2023/06/08/1178695152/china-scientist-he-jiankui-crispr-baby-gene-editing,
accessed on 29 March 2024.
17. Xiaolong Wang et al., “Generation of
Gene-Modified Goats Targeting MSTN and FGF5 via Zygote Injection of CRISPR/Cas9 System,”
Scientific Reports, 2015, https://doi.org/10.1038/srep13878, accessed on 29 March 2024.
18. Jon Cohen, “Embattled Russian Scientist Sharpens
Plans to Create Gene-Edited Babies,” Science, 21 October 2019, https://www.science.org/content/article/embattled-russian-scientist-sharpens-plans-create-gene-edited-babies,
accessed on 29 March 2024.
19. Ruwitch.
20. Caplan et al.
21. Shwartz.
22. “Biodefense in the Age of Synthetic
Biology,” 2018, National Academies Press, https://www.ncbi.nlm.nih.gov/books/NBK535877/, accessed on 29 March 2024.
23. Redman et al.
24. “Oviedo Convention and Its Protocols,”
Council of Europe: Human Rights and Biomedicine, 2024, https://www.coe.int/en/web/bioethics/oviedo-convention, accessed on 29 March 2024.
25. 2023 Biodefense Posture Review.
26. National Biodefense Strategy.
Authors
Dr. Preston is the biological defense training instructor for the CBRN Captain’s Career Course, the
CBRN Basic Officer Leader Course, and the CBRN Chief Warrant Officer Basic Course, USACBRNS. She holds a
bachelor’s degree in neuroscience from Wellesley College, Massachusetts, and a doctorate degree from
Poznan University of Medical Sciences, Poland.
Captain Sheth is a small-group leader for the CBRN Captain’s Career Course. He holds a master’s
degree in environmental management from Webster University and a doctorate degree from Poznan University of
Medical Sciences. He is currently pursuing a second master’s degree in strategic intelligence
technology from the National Intelligence University, Bethesda, Maryland.
Staff Sergeant Sayles is a CBRN advanced individual training biological operations instructor at USACBRNS. He
is pursuing an associate’s degree in counterterrorism from the American Military University.