5

Overview of the Workshop

The final session of the workshop began with Asha George, co-director of the Blue Ribbon Study Panel on Biodefense, providing a summary of the day’s discussions and her reflections on those discussions. This was followed by a wide-ranging panel discussion among the workshop planning committee members—Bruce Budowle, John Clements, David Cullin, Norman Kahn, Grace Kubin, Fred Rosa, Jr., Tom Slezak, and Colin Stimmler—and an open discussion with the workshop participants. Adel Mahmoud moderated the session.

MAJOR TOPICS OF THE WORKSHOP WITHIN THE CONTEXT OF U.S. BIODEFENSE EFFORTS

Asha George began her presentation by discussing the work of the Blue Ribbon Study Panel on Biodefense, which was established in 2014 to assess gaps and provide recommendations to improve U.S. biodefense. The Blue Ribbon Panel, she explained, is a foundation- and private-sector-funded organization that looks at biodefense across the entire spectrum of related activities, such as public health, prevention and deterrence, preparedness, response, attribution, recovery, and mitigation, in addition to those conducted by the intelligence community, the Department of Defense (DoD), and the Department of State. Panel members include former elected officials, former cabinet members, and an advisor to the Department of Homeland Security (DHS), as well as several scientists as ex officio members. The Blue Ribbon Panel also employs several former congressional staffers.

In 2015, the Blue Ribbon Panel issued a report—A National Blueprint for Biodefense (Blue Ribbon Study Panel on Biodefense, 2015)—and of the 33 recommendations, it included one that dealt specifically with detection. This recommendation stated that, “The Nation continues to lack a rapid and reliable environmental detection system for known and unknown biological threats, a situation that must be rectified,” and suggested two action items: fund the development of advanced environmental detection to replace BioWatch, and replace BioWatch Generation 1 and Generation 2 detectors. George explained that this recommendation was not meant to imply that BioWatch should jettison the current technology and replace it in total, but to take out old systems that are not functioning well

and replace them with technology that takes advantage of advances in science and better meets the nation’s needs.

George noted that all of the report’s recommendations are specific about what actions Congress, the Vice President, DHS, and DoD need to take. For example, the report calls for Congress, through its appropriations to DHS and DoD, to fund a system capable of

• Rapid agent characterization and confirmation,
• Collecting viable organisms,
• Determining geographic distribution,
• Determining environmental persistence, and
• Providing advanced molecular diagnostics to the laboratories supporting operational activities.

She noted that the Blue Ribbon Panel has been successful in spurring Congress and both the Obama and Trump administrations to begin to address the recommendations.

One issue that concerns her, though, is the lack of funding for biodetection. “The amount of money being put toward biodetection in particular does not match the emphasis we are placing on biodetection when it comes to national policy,” said George. “For something that has this much weight for the President of the United States to actually mention it in the State of the Union address, and for it to have made its way into policy documents starting at the White House and going down, the amount of funding that is being put toward it is simply not proportional, and it is not fair to ask the Department of Homeland Security, the Department of Defense, and whoever else to try and produce detectors without sufficient funding to carry out that mission.”

One of the report’s recommendations, which the Blue Ribbon Panel members discussed at length, calls for the Vice President to take up the issue of biodefense as a responsibility of the Office of the Vice President, in large part because the nation’s biodefense efforts are spread out over many departments, agencies, and the private sector. George explained that the Blue Ribbon Panel concluded that because so many entities were involved, someone in the White House with an extreme amount of influence and power was going to have to take charge of the biodefense enterprise. Specifically, the report calls for the Vice President to institute a formal process among DHS, DoD, and all other federal agencies that utilize or are developing detectors for biological agents that will result in better information sharing regarding biodetection successes and failures. This process would also enable one agency to procure another agency’s technology if it fits the appropriate requirements, which is often difficult given the way agencies are funded.

For DHS, the report stated that the department must work with state, local, tribal, and territorial end users at the earliest stages of the development of BioWatch requirements and to develop a standardized integration strategy and set

of training requirements based on those discussions. As several speakers throughout the course of the workshop had noted, involving end users in any technology development efforts needs to start early, and because that did not happen when BioWatch was first implemented, the program suffered in its early days, said George. The report also called for DHS to replace BioWatch Generation 1 and Generation 2 detectors with advanced environmental detection systems by 2020 or remove them from service. In addition, the report stated that DoD and DHS must better coordinate their environmental detection efforts and leverage each other’s advances in order to develop a detection system capable of meeting today’s threats with 21st-century ingenuity and replace the civilian system currently in place.

George noted that the workshop’s discussions addressed a number of the report’s recommendations and observations, including the obvious fact that there are a variety of possible approaches to improve biodetection. The availability of multiple options creates two paths forward, she said. One path involves looking at the array of technologies available today and a few that are close behind in their development, selecting those that are appropriate, and introducing them iteratively. This, she said, is a valid approach, one the nation has used successfully. “However, we heard yesterday that in 5 to 10 years we expect that there will be a whole new technological landscape that we will all be looking at, so taking that sort of measured approach is not going to work for more than 10 years,” said George.

The other approach, she explained, is to look over the scientific horizon, identify possible solutions, plan backward to the current day, and then go forward on the same path. This is the way the Defense Advanced Research Projects Agency and some parts of DHS work. The problem with this approach, said George, is that BioWatch has no control over the research and development dollars or activities that it would need to take that path. As a result, the program would have to convince those who do control research and development funds and activities of what needs to be done. “We recognize this challenge, but believe it is something that needs to be overcome,” said George.

One issue that she feels needs revisiting is that of continuous monitoring, a requirement George said was “levied from on high.” Trigger systems, she added, may be more appropriate and need closer examination. Another is the Office of Health Affairs’ place in DHS, which she said has advantages in terms of coordination and collaboration. However, for BioWatch to do what it believes needs to be done, the Office of Health Affairs, which oversees the program, needs to be better empowered within the department. George also noted that the technologies developed by the DoD’s JUPITR project, which is well regarded in Congress, should be transferred to, or at least evaluated by, DHS for use domestically. Doing so, however, will require actions by Congress and the White House, and the Blue Ribbon Panel continues to have conversations with members of Congress and the Administration regarding those actions. What makes this effort more difficult, said George, is that the Secretaries of Defense and Homeland Security have to put biodetection high on their departments’ priority lists. “I think this is something

that needs to be part of what the [DHS] Office of Health Affairs pursues to help itself,” said George.

Reflecting on the lack of confidence Congress and many government officials have in the BioWatch program, she called the situation unfair. “There are data that people are not looking at or comprehending, and this belief is impacting how the program is funded, and how biodetection in general is supported and moved forward,” said George. “We need to do something about changing that perception.” Acknowledging that could take time, she suggested taking advantage of DoD’s reputation to push for better support for developing and implementing improved biodetection technologies.

Concluding her remarks, George made an impassioned plea based on personal experience. “I think that we as a nation deserve decent, spectacularly wonderful and useful biodetection, and I believe it because I was in Desert Storm and stood there and watched SCUD missiles and Patriot missiles collide with each other,” she said. “I stood there wearing my chemical protective overgarments wondering, as an intelligence officer, whether there was in fact anthrax in the SCUD missile and what was going to happen to me as I was standing there. I know what it feels like to get vaccinated with vaccine that has been cleared by the [Food and Drug Administration] under an Emergency Use Authorization, and I do not want anybody here in the United States or its interests overseas to have to wonder where we are with being able to protect the public from biological events, especially when we know that the threat is increasing.”

PANEL DISCUSSION

To start the discussion, Adel Mahmoud asked each planning committee member to provide their reflections on what they had heard throughout the course of the workshop. Bruce Budowle began by noting the tension between investing in and implementing new technologies and keeping the system stable to see how it functions in an operational setting. He strongly recommended letting industry run its course and waiting to see what works as opposed to trying to force a new technology into the system. “I think industry is quite Darwinian and capable of finding what is the best niche,” he said. As far as making enhancements to the current system, he would focus on the collection phase, as well as looking at incorporating additional targets, antibiotic resistance genes, and virulence factors into the multiplex polymerase chain reaction (PCR) assay process.

In Tom Slezak’s opinion, it would be a good idea for the BioWatch public health community to examine closely the DoD system and identify features it likes and does not like. “What the DoD has done is great, but the DoD’s mission is different than public health’s,” he explained. He agreed with Budowle that multiplex PCR could be used more effectively, and added that BioWatch should examine the possibilities of using targeted sequencing. He noted that biodefense is a tiny sector in the infectious disease industry, so biodefense is not going to drive many research efforts by industry.

After listening to the workshop’s presentations, Norman Kahn said it is clear that BioWatch will not, over the next decade, develop a system that would all at once “significantly improve current performance with respect to things like time sensitivity, specificity, range of agents, indoor applications, autonomy, quality of confirmatory response, and cost,” as was listed in the workshop’s Statement of Task. In his mind, the primary goal of BioWatch is to protect the public, and based on what he had heard at the workshop, it is clear that the current system does not meet that goal when it comes to timeliness. Given that, one of his first priorities would be to implement technology such as a trigger system that would produce an initial result more much more quickly, even at the expense of some initial accuracy. From his perspective as a former member of the intelligence community, he also thought the system needs to move away from focusing exclusively on pathogens to a system that is gene based, virulence based, and antibiotic resistance based. “I can think of so many scenarios where something is designed that is totally outside that box and we would be in a situation where we are not testing for it at all,” said Kahn. In his opinion, next-generation sequencing for gene-based analysis and mass spectroscopy for toxin-based analysis were interesting approaches that have a chance of maturing over the next 5 to 10 years.

David Cullin agreed with Slezak’s comment that biodefense is a small sector within the infectious diseases sector, a nice sideline if a technology can spin out of the world of diagnostics and medical applications. “Biodefense is a tough, tough business to actually convince anybody in leadership that we should be involved,” he said. Given that, it may be necessary to adapt more to what industry is doing in other areas and make use of advances in those other areas. Cullin then reiterated Toby Merlin’s plea to make more of the existing data available to public health under the right circumstances so that public health can analyze how various technologies work and do not work in real operating environments. He also supported the call from several panelists for more communication and collaboration among the technologists, the federal government, and public health.

Colin Stimmler echoed Cullin’s call for more data, but having said that, explained how he conceives data being used in the decision-making process at a local health department. From his perspective, reports summarizing findings from the data are nice, but what he really wants is the file with the actual data so that he can do his own analysis and come to his own conclusions. “I think that would go a long way in helping us be advocates or champions with our own agency leadership, our elected officials, and everyone else we have to also convince about the validity of any program,” said Stimmler. He also touched on the need for more discussions about cost, particularly the not-insignificant cost to state and local public health laboratories at a time of diminishing tax-levied funds to support public health departments.

For Grace Kubin, one of the messages she heard throughout the workshop was how the BioWatch program has worked hard to create a collaborative community to work together on BioWatch. In that regard, she said the BioWatch Advisory Committees have to continue to be an important program component and that DHS has to continue engaging all stakeholders involved in the response after

a BioWatch Actionable Result is declared. She also recommended increasing public education about biological weapons and the efforts the program is making to keep the public safe. While she wondered if the technologies discussed at the workshop would be ready for deployment within the next 10 years, she reiterated the need to have the end users involved early and often in the development and testing of those technologies.

For his position as a dispassionate observer, John Clements said his impression is that the BioWatch trigger is the least significant part of the complex machinery that goes into public preparedness and public health. He also noted it is much more difficult than most people appreciate to take a nonpathogenic organism and make it pathogenic, and so he is not as concerned about “some guy in his garage” using synthetic biology to create a new pathogen. For him, when he looks at the biodetection landscape, BioWatch is a remarkable system that works quite efficiently, though it does need to work better. Where he would focus is on letting public health take the lead because a BioWatch trigger is meaningless unless there is an effective public health response. “I would let the public health system take the lead on this and see what technologies they develop that BioWatch can adapt rather than going the other way around,” said Clements. Given that, he would focus on optimizing PCR and shortening the time for analysis rather than finding a new system and having to convince public health to have confidence in it.

Fred Rosa commented that he heard a great deal of positive feedback about the BioWatch program throughout the course of the workshop, in terms of both protecting the public and serving as the catalyst for increased collaboration, cooperation, and coordination among the many stakeholders involved in biodefense. One concern he voiced was that he is not sure from a national policy perspective that enough strategic significance has been placed on subways, and to a lesser extent airports. “I say that knowing there is plenty of discussion and plenty of focus and that there are appropriations and there are studies and so on, but it seems to be that a successful attack in one of five or six of the nation’s subway systems could have truly dramatic and long-lasting impact in terms of loss of life and enduring economic impact,” said Rosa.

From his perspective of having served for 34 years as a commissioned officer in the military, Rosa added that his primary concern as a decision maker would be having high-confidence information in a timely manner so that he could make decisions at the tactical, operational, and ultimately strategic level. Given that, he said future technological developments should put a premium on producing high-confidence results in a more timely manner.

After hearing the comments from the eight panelists, George said it is clear there is room for debate around the different approaches the BioWatch program can take with regard to improving the system, and that debate needs to continue to move the technology forward. Michael Walter said he agreed with everything the panelists said and that there is a great deal of work to do with the program and in the field of biodetection in general. He then said that the true state of the art of environmental biodetection today is something that tends to be misunderstood. “Right now,” said Walter, “what BioWatch does is exactly what DoD does and

other agencies do, which is collecting a sample on something, taking it to a laboratory, and conducting an analysis.” In that respect, biological threat detection is 20 to 30 years behind the state of the art for radiation and chemical threats. Nonetheless, he said he has been accused fairly recently of not deploying some handheld device that can do what technology can do with chemical and radiological detection.

Walter also noted that BioWatch is now part of an intergovernmental group called the Biodefense Alliance and whose members include the BioWatch program, the DHS Science and Technology Directorate (S&T), the Joint Science and Technology Office, the Defense Threat Reduction Agency, and the Joint Program Executive Office. As part of that group, he has been briefed on what the JUPITR program has been doing, and the program has committed to providing triggers, collectors, and portable identifiers that BioWatch can test in the test beds that are being set up in the harsh environment of the New York City subway system and in a live agent test at the Battelle Memorial Institute scheduled to start in early 2018. Walter said he has already had talks with the Acting Assistant Secretary of the DHS Office of Health Affairs about acquiring those DoD technologies should they prove appropriate for BioWatch’s mission and the environments in which it works. He also noted that he has been talking with DoD about some joint research efforts, though the main issue is that BioWatch and the DoD have different missions, and the environments in which BioWatch operates are more complex. One surprising message Walter heard was the continued support for PCR technology, having expected the panelists to push hard for the program to adopt sequencing technologies.

DISCUSSION

Adel Mahmoud began the open discussion by asking the panelists for their thoughts on expanding the list of targeted agents. Clements replied that the current list has 90-something things on it, and, in his opinion, “that list makes us less safe rather than more safe because it gives us permission to not think about some things that are probably just as pathogenic and weaponizable as things that are on that list.” The current list, he said, has become a public health list rather than a select agent list because it contains organisms such as the SARS virus that cannot be grown, let alone weaponized. Where he would focus attention on is the few agents with which the U.S. government or the former Soviet Union has experience. “We know what those are, and we know what their profile looks like,” said Clements. “I would focus on those things that are on that known list before I would launch off into any of the other esoteric things.”

When Mahmoud raised the possibility of someone doing “gain-of-function” work with an influenza virus, Clements said it is impossible to anticipate that kind of work. He also reiterated how difficult it is to both weaponize an organism and keep it viable. He then noted that determining viability is still a time-consuming task, and the current technology of collecting samples on filters almost guarantees

that whatever is on the filter would not be viable, with the possible exception of spores. With that in mind, he recommended focusing on developing new collection technologies that would keep organisms viable and then looking for new ways of demonstrating those organisms are viable.

Returning to the issue of adding additional agents to the detection list, Stimmler said some of the agents on the current list do not have a consensus recommendation from the Centers for Disease Control and Prevention on appropriate treatments or prophylaxis. Therefore, he would like to see more research on countermeasures for targeted agents. He also remarked that adding more agents onto the panel increases the probability of having a false positive.

An unidentified participant commented on the need to include the intelligence community in conversations about biological threats. Kahn replied that so much of the information the intelligence community has is highly classified, so any discussions involving the intelligence community would be of limited value. He also repeated a comment he made earlier, which is that for the foreseeable future, the intelligence community will have very limited insight into what adversaries are doing with respect to the development of biological agents. “You cannot count on the intelligence community to be substantively informative as to what the threat looks like in real time because the data is not going to be there,” said Kahn.

Rachel Levinson from Arizona State University said she is somewhat concerned about a system that does not incorporate flexibility to deal with an engineered organism in the future. “If we are talking about changes, advances in technology over the next 10 years, that is fine to talk about improvements in what we have, but I think there also ought to be some consideration for the fact that the technology for engineering organisms is improving at a great rate,” she said. Slezak replied that he and his colleagues have been looking at metagenomics as a means of spotting unknown organisms and, based on his experience, there are so many homologs to virulence mechanisms existing in nature that there will be too many false positives.

Clements remarked that if a virulence factor was added to a known organism that the system currently profiles, the system will still detect it. He noted, too, that virulence is a multifactorial phenomenon, so adding a toxin gene, for example, into Escherichia coli will not make it more pathogenic than it already is given the natural barriers that regulate virulence. Moreover, producing enough material to create a threat requires tremendous resources and technological expertise. In addition, such agents will need to be tested, which in itself would be challenging. His final comment was that there may be a day when someone walks into an emergency department with a very odd infection and deep sequencing will be needed to identify it. Having said that, he added, “I do not know if you can set up a platform that routinely screens for things that are so odd that you have never seen them before.”

With that as the final remark, Mahmoud adjourned the workshop.