Investing in our nation’s future military leaders’ synthetic biology knowledge to understand and recognize threats and applications

Abstract

Synthetic biology encompasses some of the greatest advancements in biology. With improvements in molecular methods and techniques that allow targeted and highly efficient genome manipulation, the capabilities of engineering biology have significantly increased. These enhancements in biotechnology represent significant potential benefits and risks to the global population. It is important that future leaders are trained and understand the incredible benefits, opportunities and risks associated with synthetic biology. The US Department of Defense (DoD) has issued a technical assessment on the future opportunities of synthetic biology and has encouraged the military institutions to expand and encourage bioengineering research programs. At the US Air Force Academy (USAFA), opportunities are provided for future Air Force officers to recognize the potential and risks associated with synthetic biology by participating in the USAFA Synthetic Biology Education Program (USBEP). Cadets can enroll in synthetic biology courses to learn and master molecular biology techniques and work on independent undergraduate research projects. In addition, cadets have the opportunity to join the USAFA’s International Genetically Engineered Machine (iGEM) team and compete in the international synthetic biology competition. This report includes details on how USAFA has recruited, enrolled and encouraged synthetic biology research and education among future leaders in the US Air Force.

1. Introduction

Through the use of living organisms and biologically based tools to intentionally create products, synthetic biology is revolutionizing medicine, public health, biotechnology and even food production (1, 2). However, the potential applications of synthetic biology also include those that can cause harm, either unintentionally by accidental release or unforeseen interactions, or intentionally by enemy states, groups or individuals. Synthetic biology increases the possibilities of the biological world beyond what evolution created and is limited almost only by human imagination (3).

Biological warfare has been used as a weapon in conflicts for centuries, with wide-ranging and often unforeseen and uncontrolled effects on military and civilian populations (4). Despite the 1974 widely ratified ‘Convention on the Prohibition of the Development’, ‘Production and Stockpiling of Bacteriological (Biological)’ and ‘Toxin Weapons and on their Destruction’ treaty (5), research into and deployment of biological weapons has continued by some countries and nonstate actors (4). Notably, the modern era has seen a rise of nonstate sponsored groups and individuals utilizing bioterrorist strategies to further their agendas (4). Therefore, it is crucial that we continue to remain vigilant to guard against biological weapons and other biological threats that threaten national security. The current state of the USA’s biodefense and biosecurity goals is encompassed in the 2018 National Biodefense Strategy. The key goals of the National Biodefense Strategy are to:

Enable risk awareness to inform decision-making across the biodefense enterprise;

Ensure biodefense enterprise capabilities to prevent bioincidents;

Ensure biodefense enterprise preparedness to reduce the impacts of bioincidents;

Rapidly respond to limit the impacts of bioincidents;

Facilitate recovery to restore the community, the economy, and the environment after a bioincident (6)

The concern is that the advent of synthetic biology techniques may be used to create biological threats that may be more dangerous or more accessible to more individuals and nonstate sponsored actors than in the past (2). The Department of Defense (DoD) has a duty to stay aware and to actively seek to counter threats from adversaries. In addition to the obvious biological attack from an enemy state, the DoD has a special interest in preventing, detecting and treating biological threats to ensure military personnel readiness and in providing assistance during humanitarian medical crises (2, 7). Areas of special concern, including the Federal Select Agent Program’s Select Agents and Toxins list (8), may not be sufficient in an era of synthetic biology and genetic modification, as an organism not on the list and considered harmless could be engineered to become pathogenic (2). Synthetic biology expands the possibilities of potential bioweapons beyond the terrors nature created.

In addition to defending against biothreats, there are many potential uses of synthetic biology that are DoD-specific. Synthetic biology could create high-performance armor, corrosion-resistant material, environmental or medical sensors, prophylactics or other materials with a defense application (7). Biological production of materials, drugs or sensors could be cheaper, quicker or more effective than traditional manufacturing and those products may be of superior or novel quality.

Furthermore, synthetic biology embraces a collaborative work environment that integrates biology, chemistry, physics, mathematics, computer science and even management and human practices to create novel biological devices, genes or organisms. In 2010, the American Association for the Advancement of Science (AAAS) released a document entitled: ‘Vision and Change in Undergraduate Education, A Call to Action’ that outlines and encourages higher education to adopt and focus on specific scientific competencies to prepare future biologists (9–11). Studying synthetic biology provides access and training in many of the main competencies including exposure of students to the interdisciplinary and collaborative nature of the scientific process, integration of research into the curriculum, understanding complex datasets and using computational and modeling skills to answer important societal questions, and embracing new technology to develop new approaches and answer questions that were not possible before. The National Science Board (12) and National Research Council Rising above the Gathering Storm (13) have emphasized that increasing scientific innovation is critical for the Nation’s future economic and strategic security.

There is a discrete need for synthetic biology knowledge amongst DoD personnel; not only the defense intelligence agencies personnel but also the Airmen, Soldiers and Sailors at the front lines of combat. As identified by the DoD, the goals regarding synthetic biology are to: build human capital with knowledge and expertise regarding synthetic biology threats and usefulness in designing countermeasures to the threat and study human performance improvement (7). A technical assessment from the DoD specifically stated the following: ‘there are a limited number of highly-experienced program managers, leading scientists, and especially individuals in uniform with deep knowledge of the field. There is a lag time of 15–20 years between training junior officers and those individuals achieving senior ranks, so providing opportunities now is important for the future’ (7). In response, the goal of the USAFA Synthetic Biology Education Program (USBEP) is to prepare our future military leaders to recognize the potential benefits and risks of synthetic biology, especially regarding its current and future military applications.

2. Results

In an effort to increase the expertise and synthetic biology aptitude among US Air Force Officers, a priority was made to teach, train and involve the US Air Force Academy (USAFA) cadets in synthetic biology research. In order to accomplish these goals, USAFA Synthetic Biology Education Program (USBEP) was created during the 2017–18 academic year. The USBEP is composed of a biotechnology and synthetic biology year-long course and an applied synthetic biology competitive team. The synthetic biology course provides the background knowledge and exposure to critical biotechnology concepts and ideas and applies those concepts with cadet-directed experimental synthetic biology research project, namely by participating in International Genetically Engineered Machines (iGEM). iGEM is a global competition where teams research, collaborate and also compete with other teams to engineer, design and synthesize biological parts and systems using microbes and genetics (14). The research project provides an ideal environment for students to get involved and master synthetic biology principles in the lab. USBEP is cadet-led, with the cadets choosing an important DoD-related research question for the year, then designing and building a project using synthetic biology to address their research query. They are required to present research ideas to the team as a whole, then the faculty, and finally Air Force leaders to ensure the research project meets relevance criteria. The competitive nature of iGEM allows teams to set goals and work to reach different levels of achievement. The iGEM competition, called the Giant Jamboree, occurs every October in Boston, MA. The jamboree brings in over 3500 synthetic biologists from over 40 different countries, representing 350+ iGEM teams (15). The annual event provides a great opportunity for students to learn about advances in synthetic biology, connect with other like-minded students and scientists and receive valuable feedback and direction for their research projects.

Most iGEM teams work to research, engineer and create their novel biological part(s) or system in the summer of the academic year, when normal semester classes are out. At the USAFA, cadets have responsibilities over the summer to work in basic training, take aviation courses, go on exchanges at other military installations, and other important but time-consuming activities. To allow the USBEP USAFA cadets the opportunity to participate in iGEM, but not rely on summer research time, cadets can enroll in a course during the Spring and following Fall semester that will provide dedicated class time for learning/mastering synthetic biology. At USAFA, each course is given 40 lessons. The spring semester is dedicated to learning the basic principles and protocols in context as they begin working on the iGEM project (Table 1) and then the fall semester is committed to performing additional research and attending the jamboree (Table 2). This schedule provides time for lecture and learning the principles behind the techniques, and also dedicated lab time and protocols to practice and put the principles into practice. The students are taught basics of scientific research including the following topics: maintaining a lab notebook, experimental design, implementing good controls, data analysis and biostatistics, as well as science communication and presentation skills. Several lab techniques and protocols are implemented into the course based on the current needs of the research project. The topics selected for the course are specifically chosen to help the iGEM team and project be successful, but overall, the lessons represent foundational synthetic biology concepts that would be taught in any bioengineering or molecular methods course taught at different institutions. The ultimate goal of the course is to prepare future officers in the US Air Force to recognize the potential benefits and risks of synthetic biology.

Table 1.

Spring course (first semester)

Lesson	Topic	Lect.	Lab	Assignment
1	Into to iGEM	X
2	Lab tour and safety	X	X	Lab safety sheet due
3	Lab notebook	X		Lab notebook initial check
4	Scientific literature	X		Find four relevant scientific references
5	Pipetting, volumes and calibration		X
6	Making media and solutions		X
7	Aseptic technique and streak for isolation		X	Streak plate with isolated colonies
8	Growing and quantifying bacteria		X
9	Experimental design and controls	X	X	Idea for project due
10	Experiment set up	X		Lab notebook check
11	Run experiment		X
12	Data analysis	X
13	Data presentation	X		Results from culturing bacteria/growth curve due
14	Polymerase chain reaction	X	X
15	Electrophoresis	X	X
16	Restriction site prediction	X	X
17	Restriction digest and analysis		X
18	Plasmid and ligations	X
19	Bacterial transformations	X	X
20	Analysis of transformations/quantify		X	Lab notebook check
21	Experiment set up	X
22	Run experiment		X
23	Data analysis	X
24	Data presentation	X		Results from PCR, digest and transformation are due
25	Synthetic biology parts	X
26	Promoters, transcriptions and translation	X		Worksheet on replication, transcription and translation
27	Gibson assembly	X
28	Golden gate assembly	X
29	Sequencing and validation	X		Sequencing alignment due
30	Develop project proposal	X		Lab notebook check
31	Project specific work		X	Draft of project proposal due
32	Project specific work		X
33	Prep community outreach		X
34	Community outreach
35	Project specific work		X
36	Project specific work		X
37	Project specific work		X
38	Develop plan for summer research	x	X	Formal written proposal (project/future directions)
39	Final analysis of data and current progress	x		Final manuscript due summarizing the project
40	Presentations of results and summer plans	x		Proposal and paper due

Table 2.

Fall course (second semester)

Lesson	Topic	Lect.	Lab	Assignment
1	Finalize summer research data		X
2	Project specific work		X
3	Project specific work		X
4	Presentation of summer results	X		Presentation of summer results
5	Develop final plan to finish project	X		Plan/timeline to complete final work on project
6	Biostatistics	X
7	Biostatistics	X		Complete biostatistics worksheet
8	Data analysis and statistics	X	X
9	Project specific work		X
10	Project specific work		X
11	Project specific work		X
12	Project specific work		X	All results needs to have statistics performed
13	How to prepare a scientific poster	X		Begin poster template for project
14	Work on poster/project specific work		X
15	Work on poster/project specific work		X	Sign up for portion of info session
16	Work on poster/project specific work		X
17	Info Session/recruitment for next team	X		Bring a friend for info session/present assigned parts
18	Work on poster/project specific work		X
19	Work on poster/project specific work		X	Poster draft due to instructor
20	Work on poster/project specific work		X
21	Work on poster/project specific work		X
22	Work on poster/project specific work		X
23	Science communication/public speaking	X		Poster draft #2 due to instructor
24	Prepare talk slides	X
25	Prepare talk slides		X	Talk slides due to instructor
26	Practice presentations		X
27	Final preparations		X	Final poster and talk due
28	Final preparations		X
29	iGEM Jamboree
30	iGEM Jamboree
31	iGEM Jamboree
32	No class- get caught up from Jamboree
33	Reflection/feedback for annual project	X		Complete survey
34	Scientific writing/publishing	X
35	Work on final paper/summary of project		X
36	Work on final paper/summary of project		X	Final Paper draft due
37	Review next year team applications	X		Read and be familiar with applicants
38	Interview candidates	X		Prepare interview questions
39	Select next year teammates	X
40	Future directions/continuation of project	X		Final paper due

Enrollment in the course is a co-requisite for participating on the iGEM team. To enroll in the course, students have to fill out an application (Supplementary data) and are selected and interviewed by the current USBEP team during the fall semester (Table 2). Synthetic biology is a highly collaborative effort requiring scientists with a wide variety of backgrounds and expertise, therefore, the USBEP team and research projects are intentionally a multidisciplinary and collaborative effort. To achieve this diversity, recruitment for the USBEP team is conducted in all departments on campus. In 2019, the team is composed of 22 students from six different departments (Figure 1A). Students from any level are allowed to apply, although Seniors (First Class Cadets) that are seeking to join would not have the time to participate in the fall jamboree, so slots are usually reserved for Juniors and Sophomores (Second and Third Class Cadets, respectively; Figure 1B). The experienced cadets on the team become team leads and have the opportunity to train and supervise newer students that are joining the team or are interested in the work. Interestingly, USBEP was highly sought after by cadet women. In an institution that is dominated by men (Figure 1C), it is notable that the majority of our team are women (Figure 1D). Interestingly, iGEM teams with a better gender balance tend to perform better at the annual competition than teams that are predominantly male (16). This diversity in USBEP strengthens the learning environment and increases the productivity of the research team.

Fig. 1.

2019 Team demographics and composition. (A) Academic majors of students participating on the iGEM team. (B) Composition based on academic year/credits earned. (C) Gender breakdown for all of USAFA. (D) Gender breakdown for participants on the iGEM team (data represents 2019 only. 2018 team data not shown).

The team is subdivided into smaller groups that work on various aspects of the project (detection, degradation, cloning, data analysis, biosafety and team documentation, human practices, etc.). This division of labor allows specialization for different areas and provides more leadership opportunities for the students. On a regular basis, the whole team will get together and each group of students will provide status updates for their individual projects. The team can collaborate, provide guidance, feedback and adjust as needed in order to meet the goals of the collective team. In addition to the benchtop research that is being conducted, part of the goals is to create a website and connect synthetic biology to human practices and the community needs. The USBEP projects are presented in a variety of settings to allow the team to practice scientific communication skills to different audiences including K-12 students, general public, undergraduates at other institutions, Air Force leaders and at scientific conferences. These nonlaboratory goals allow the cadets to practice scientific communication skills, which are critical to their future as US Air Force Officers.

Overall, since the implementation of the USBEP at USAFA during 2017–18, there has been an increased awareness and excitement regarding synthetic biology and research in general. The reputation of the USBEP has spread and it is expected that participation will continue to grow and involve more cadets in future years. The iGEM platform currently provides a well-organized and designated area for students to get involved in synthetic biology research and have fun in a competitive team environment. In addition, the course provides dedicated time and motivation for students to come to class, learn the material and prepare for the applied research project. With an increased emphasis on synthetic biology and the DoD encouraging future military officers to be trained in bioengineering, early indications show the USBEP to be highly effective at teaching, training and encouraging USAFA cadets to master and be aware of the incredible opportunities that are available because of synthetic biology.

3. Discussion

Recent advances in molecular biology have significantly increased the ability to engineer and modify living organisms (17, 18). The field of synthetic biology is expanding rapidly and not only provides great opportunities for commercial applications, conservation, human performance, detection, medical but also presents biological and/or chemical defense concerns. The DoD has issued a technical assessment and has encouraged training and increasing the capabilities of the US Air Force and other military branches to be leaders and key participants in the advances in synthetic biology (7). In an effort to increase the Air Force’s involvement in synthetic biology, the USAFA has created USAFA Synthetic Biology Education Program (USBEP) that teaches and trains future Air Force officers in critical synthetic biology methods and techniques.

The synthetic biology course has been popular among USAFA cadets and enrollment is predicted to increase. The USBEP was successful in attracting cadets from different academic disciplines. The collaborative nature of synthetic biology provides great opportunities for students from different departments and interest areas to work and learn together. Interestingly, USBEP is composed of a majority of cadets that are women. In an institution dominated by men (74%, Figure 1), it is exciting to see the increased proportion of women participating in synthetic biology. We are excited about the opportunity to train future Air force leaders from many backgrounds in synthetic biology.

Overall, the implementation of the USBEP’s two components, the educational course and the competitive team, has been very successful. Cadet’s co-participation in both the team and the course provides a great platform to learn basic principles and then practice and take ownership of the protocols as part of the team project. Conducting hypothesis-driven research in synthetic biology can be time-consuming and frustrating but the opportunities to learn, improve and develop leadership and collaboration skills are abundant. Synthetic biology represents a huge part of future biological research and it is our goal that the USBEP USAFA cadets will become the leaders that will take responsible and productive synthetic biology advancements into the future.

Synthetic biology represents an emerging field in biological research that is going to have large impacts on the future. Although the goal of the USBEP is to prepare future military leaders to recognize the potential benefits and risks of synthetic biology, the program design and implementation could be modeled at a wide variety of undergraduate institutions in order to increase the awareness and expertise of synthetic biology in the future global workforce, both military and civilian. Based on our experience, undergraduate students are very enthusiastic about synthetic biology and similar programs could be utilized to increase STEM education and retention.