Since I arrived at USAMRIID back in 1998, the threats we face from biological weapons have not significantly diminished. In fact they may have increased. Despite the recent discussions between the Trump administration and North Korea, a report by Harvard’s Belfer Center released in October 2017 sounded the alarm about North Korea’s potential biological weapons activities. Utilizing unclassified reports, defector testimonies, and interviews with subject-matter experts, the report authors argue that preparation for the biological weapons threat is “urgent and necessary.”1 Although the media has focused on North Korea’s nuclear program, use of the nerve agent VX to assassinate Kim Jong-Un’s half-brother in early 2018 should provide a wake-up call that we ignore North Korea’s interest in other weapons of mass destruction at our peril.
Prior reports have noted North Korea’s possession of and capability to cultivate thirteen agents, including some of the Chessmen on the category A threat list: Bishop Plague (Yersinia pestis), Queen Anthrax (Bacillus anthracis), King Smallpox (Variola major), and Pawn Botulism (Clostridium botulinum).
Possession is only one aspect. Weaponization and stabilization for deployment are others. The Belfer report notes that North Korea may have the capability to weaponize the agents. Deployment methods such as by rocket launchers, sprayers, or infected humans used as vectors are theoretical possibilities. The South Korean Ministry of Defense stated that the thirteen agents could be weaponized “within ten days.”
The late William Patrick, chief of product development for the United States’ former offensive biological weapons program once told me that the U.S. program proved the effectiveness of biological weapons “beyond the shadow of a doubt.” We don’t need to experience a nightmare scenario on the Korean peninsula to prove Bill’s point. As the Harvard report points out, we should not feel reassured just because we have limited intelligence on North Korea’s capabilities. We should be even more concerned. Despite having suspicions about the former Soviet bioweapons program, we were still shocked at the extensive Soviet biological weapons arsenal revealed by Dr. Ken Alibek in his book Biohazard, after his defection in the 1990s.2
We don’t have to look far to know that interest in deploying weapons of mass destruction is alive and well, with periodic chemical agent attacks occurring in Syria against civilian populations and the assassination attempt in 2018 on a former Russian spy in the United Kingdom with a Novichok nerve agent. We still don’t have a window inside Russia’s military bioweapons capabilities.
Even if we don’t get hit with a bioweapon attack, we should have learned from Ebola, Zika, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) that Mother Nature is a very efficient bioterrorist.
Clearly, the need for expertise and preparedness for emerging infectious diseases and bioterrorism has not diminished. We suffer the curse of always “preparing for the last war,” and we do a poor job of predicting how, when, or where the next pandemic will start. It is merely a matter of time until the next mysterious illness emerges, leaving a trail of victims with symptoms that puzzle experts and terrify the public. We know only one thing for certain: something else will come along when we least expect it, and it will be something we don’t anticipate.
The anthrax attacks and the Ebola outbreak in West Africa helped to kick-start improved infrastructure, disease surveillance systems, coordination, and technology for more rapid diagnostics and microbial forensics, but politicians have short memories, so knowledge of the threat doesn’t necessarily translate to sustained funding for preparedness. At the same time, each new technology for improving diagnosis or scientific analysis brings a potential downside. The ability to manipulate genes has gotten easier with new genetic-engineering technologies such as CRISPR, making manipulation of harmful microbes accessible to a wider range of potential terrorists. The tools of microbiology also grow ever faster, smaller, and cheaper, so the notion of the bioterrorist making a weapon in his or her garage becomes more feasible every day.
We have some good news related to Ebola: a promising vaccine currently in use for the outbreak in the Democratic Republic of the Congo, as well as a couple of promising treatments. Early work for them was conducted at USAMRIID. We have a better system in place now to take orphan products past the difficult funding hurdles and human studies needed to get them licensed with the help of the Biomedical Advanced Research and Development Authority (BARDA), but at the same time, developing new vaccines and treatments remains difficult and very expensive. The terrorists have the advantage of selecting the agent they prefer, deploying it where we are most vulnerable, and not having to worry about regulations. And while we recognize better the importance of conducting research in real time during an outbreak to move products closer to licensure, it remains a formidable task to overcome cultural barriers, ethical challenges, and regulatory and financial hurdles rapidly enough to make a difference, especially in remote regions of the world, where unusual diseases surface frequently. And research will, appropriately, always take a back seat in priority behind caring for the victims and stopping the outbreak.
The challenges I describe in this book continue today. In order to continue developing bioweapon countermeasures, with each move made by the terrorists, our scientists need the flexibility to innovate in their countermoves, just like on a chessboard. This is as true for the military (perhaps more so) as it is for the civilian sector. Fear, rather than common sense, has created a suffocating regulatory environment around select agent use, to the point that it can leave our nation more vulnerable in the long run. We can’t let fear of mistakes drive science and drive policy. Just transferring a single test tube of blood from an Ebola victim requires an eighteen-wheeler at a cost of $5,000–$15,000. “Zero tolerance” for laboratory errors is not good policy. People are fallible, so we must accept a measure of risk to get reward. We can’t have a laboratory “stand down” for every potential lab exposure. That’s like saying, “If you don’t want to get hit by a car, then never leave the house.” Scientists working in the laboratory interpret the message of punishment, so reporting mishaps goes underground and ultimately puts the laboratory researchers and everyone else at greater risk. When we work with deadly diseases, we shouldn’t be surprised that some unexpected outcomes occur. The best policy is to learn from each error and design ways to mitigate future errors. Overall, we must remain vigilant and keep up the fight, lest the microbes and our adversaries win. In 2018 the White House released a new “National Biodefense Strategy” for a coordinated effort to accomplish the vision that “the United States actively and effectively prevents, prepares for, responds to, recovers from, and mitigates risk from natural, accidental, or deliberate biological threats.” This is a step in the right direction, but we must remain mindful of the need to stop infectious diseases where they occur before they spread because they don’t respect national or continental borders.
In 2009 Wendy Sammons-Jackson, an army major and microbiologist, was in her second tour of duty at USAMRIID. A medium-height runner, with bobbed blond hair and a perpetual smile, Wendy was enthusiastic about her first research project studying Francisella tularensis bacteria that might eventually lead to an improved tularemia vaccine. Wendy worked under the hood growing the Francisella organism in a broth culture and then carefully removing the fluid broth with a syringe and passing it through a filter. Before starting work, she was evaluated for possible vaccination against tularemia, but her blood tests showed she already had antibodies, possibly from a tularemia infection years prior, so she was not vaccinated.
On a Friday afternoon a week before Thanksgiving, Wendy began to feel ill, and her smile disappeared. It started with a headache, influenza-like symptoms, and diarrhea. Over the next two days, the headache worsened, like someone was beating her over the head with a hammer, and she had wide temperature swings three to four times a day, with fevers as high as 105 degrees. Loss of appetite and extreme muscle and joint pain in her ankles and hips knocked her flat, and she couldn’t get out of bed.
She suffered at home through the weekend, and like a good soldier, she called in sick the following Monday and went to the clinic on Tuesday. It was the height of the 2009 swine flu epidemic. The doctor who saw her, understandably, presumed she had the flu. No lab tests were done, and she was sent home with the usual instructions to take ibuprofen as needed.
Thanksgiving approached, but because she felt too ill, she abandoned plans to host the family. Her mother volunteered to host in Delaware instead. Still ill with fevers and chills, Wendy managed to make the trip with her husband and two infant boys, even as she feared spreading the flu to other family members. While in Delaware she noticed new sharp pains in her chest when inhaling, which prompted a trip to a local emergency room. She explained to the doctor that she had been told she had the flu, but she now feared she might be developing pneumonia. The doctor took a chest X-ray, which was negative.
“Continue treating as you have been,” he told her.
From there things went further downhill. The week after Thanksgiving, she couldn’t catch her breath when she sat up. She called into work again—this time talking to one of USAMRIID’s physicians. He expressed concern that her illness might not be the flu, but it could be related to her lab work. He told her to go to the hospital and that he and the other USAMRIID physicians would be standing by to talk to whomever she saw.
After she told the doctor in the internal medicine clinic about the pain, the fevers, and her fear of pneumonia, he told her that she didn’t have pneumonia. Continue as you have. She pushed back, saying the USAMRIID doctors wanted to talk to him.
He was not interested. “I think you are stressed out taking care of your family and that’s why you’re not recovering.”
Wendy pleaded with him to rule out tularemia. He said that she didn’t even have a fever. She knew that, because the fevers were cyclical, but she assured him that the fever would return within the hour.
“Sometimes people think they have a fever when they have a hot flash,” the doctor explained. He gave her a card and recommended stress-management counseling.
Desperate, Wendy called back to USAMRIID and the doctors there told her to come to the institute immediately and had her get a chest X-ray at the neighboring clinic on Fort Detrick. The X-ray showed fluid and lymph node swelling inside her chest, along with pneumonia. After seeing this, USAMRIID docs started her on antibiotics and drew blood to test for tularemia. A couple of days later, the tularemia test came back positive. Her fever initially dropped on the antibiotics, but within days, she was feeling worse again, so she was finally admitted to the hospital. Her original chest X-ray was reevaluated and found to indicate pneumonia, which the emergency room staff had not picked up on. After several weeks of treatment and disabling side effects, Wendy gradually improved, but her odyssey would continue for another two years with low blood counts, ongoing fatigue, and pains in her back and joints.
Wendy’s story is not that unusual. She considers that she might have had an earlier diagnosis if someone had actually tested her for influenza. A negative test might have prompted a search for an alternate cause, because once she had been labeled as having “influenza,” it was hard for physicians to think otherwise. It wasn’t until USAMRIID’s physicians became involved that the course began to change. She also admits that, although she worried about the possibility that her illness could have been tularemia, she didn’t want to believe that something she had done in the lab might have led to the exposure. The safety review never determined exactly how she was exposed, but a large instrument inside the hood at the time may have altered the normally protective air curtain. It was a small perturbation, but with an agent like tularemia, which only requires a few organisms to infect, it could make all the difference.
What if Wendy had shown up at a clinic with tularemia as a sentinel case after a bioweapon attack rather than from a laboratory-acquired infection? Would her illness have been recognized in time to prevent other illnesses? I like to think so, but I am skeptical. Just as in our phone call with Tom Brokaw back in 2001, it is hard to tease apart the important clues that might indicate we are dealing with the rare “zebra” instead of a more common ailment—hence the need to maintain an index of suspicion for the unusual.
Figuring out whether an outbreak is natural or spread by the enemy requires recognizing “red flags” that the outbreak was man-made. After an air attack, victims’ locations at the time of the attack could show an illness pattern along a downwind plume. A higher death rate than usual could indicate that a pathogen has been manipulated to make it deadlier. A pathogen in a place it doesn’t belong or multiple unexplained outbreaks should also ring alarm bells.
Many of the potential bioweapon threats, like anthrax, plague, and tularemia, preferentially infect animals over humans. So animal disease after or at the same time as infections in humans could be a clue of an intentional release. Of course the perpetrators make our job easier if they leave behind direct evidence, like the tainted anthrax letters or Dianne Thompson’s pastries.
Determining scientifically that a bioweapon attack has occurred is not easy.3 My colleagues and I tested a scoring method against six suspicious outbreaks.4 Only the anthrax letter outbreak would have been categorized as “highly likely” due to bioterrorism.
So what is the solution?
Recognizing something unusual relies on a human putting two and two together. In 1994, while working in Florida, Dr. Scott Folk, an infectious disease doctor, treated a couple of patients severely ill with fevers, chills, headaches, muscle aches, nausea, low platelets, and liver injury.5 They fit the pattern of a rickettsial illness, like Rocky Mountain spotted fever. The tests for such diseases came back negative, but the patients improved after he treated them with doxycycline, the antibiotic that usually works for rickettsiae. Puzzled, Dr. Folk contacted the CDC and they ran a battery of tests. They eventually made the diagnosis of a different rickettsial disease called Ehrlichia. Although Dr. Folk was not the first to discover the pathogen, it was new to his location, so he and his CDC collaborators published a couple of articles on it.
Fast forward ten years to 2004. Dr. Folk was then working in Missouri. Again, he saw a few patients with rickettsia-like symptoms, but something was amiss. They didn’t respond to doxycycline as they had before, so he contacted his former CDC collaborators. This time, they grew a brand-new virus in the lab. They named it Heartland virus. Antibiotics don’t work against viruses, so it was not surprising, in retrospect, that the patients didn’t respond to doxycycline.
Dr. Folk’s ability to make that discovery depended on a rare convergence of events: his experience ten years earlier, which primed him to consider something unusual, plus his access to sophisticated diagnostic testing through his preestablished contacts at the CDC. We need a similar convergence of events and experience to identify bioterrorist attacks early.
Surveillance systems are important for giving us normal disease rates in a specific population, so we have something to compare with before we sound the alarm. There is a tradeoff, though. The more sensitive we make a surveillance system, the more times we chase down false alarms. The less sensitive it is, the more we risk missing the outbreak early enough to make a difference. Surveillance systems, though, won’t usually give us the early warning we need. Humans do that.
As two physicians noted in an article after the anthrax letter attacks: “Despite our significant advances in technology and the development of systems designed for bioterrorism preparedness, we firmly believe that an astute clinician will once again be the first to recognize the next patient with an illness resulting from deliberate exposure to a biologic agent. It has been said that luck is where the road of opportunity crosses the road of preparation. In public health this intersection is often at the bedside.”6
I agree.
But it is more than luck. The physician at the bedside needs a trained eye to recognize the zebra, coupled with the determination to pick up the phone and call for help.