On October 18, 2001, three days after John Ezzell’s Daschle letter crisis, I was working on my home computer when my phone rang around 9:00 p.m.
“How many doses of botulinum antitoxin do we have?” USAMRIID’s deputy commander asked, his urgent tone of voice stirring a visceral unease that I used to feel in the hospital when a patient’s condition was deteriorating rapidly.
What? I thought. We were still knee-deep in anthrax. Now botulism?
My division took care of a stockpile of special vaccines and treatments that the army had developed and kept for rare bioweapon infections that military personnel or our researchers might be exposed to. These included three unique antitoxins to treat botulism not available anywhere else.
I thumbed through my brown leather-bound day planner, its cover tattered from use, like a priest’s well-worn Bible. As important to me as the presidential “football” with the nuclear codes, my planner contained everything I needed for quick reference: the on-call roster, key points of contact, treatments for threat agents, and entry requirements for each of the USAMRIID laboratory suites. I reviewed a spreadsheet inside that listed the contents of our massive walk-in freezers that we affectionately called “Little Alaska” and “Little Siberia.” I told the deputy commander the latest numbers of antitoxin vials.
When I hung up the phone, I sensed that something ominous was in the offing.
Botulinum toxins—the “pawns” among the top feared germ weapons—kill in a horrific way, paralyzing people from the head down while they are wide awake, something akin to being buried alive. Each toxin floats around in the blood in search of a nerve target. Our nerves communicate with one another, like a massive set of electrical circuits, but through chemical signals instead of wires and plugs. Like a ferryboat delivering cars, the chemicals carry a signal across a channel between nerves smaller than a human hair to stimulate nerves on the opposite side.
Once inside the nerve cell, botulinum toxins block the chemical release from the nerve terminal, paralyzing the muscles on the other side. Victims notice the blockade effects initially with blurred or double vision, then a dry mouth and difficulty swallowing. They become progressively more helpless as their speech fails, they choke, or their head droops. With larger doses the paralysis descends to the diaphragm muscles that control breathing. The victim suffocates.
As I thought about the horrors of botulism (“bot”), I picked up the phone to call one of my employees, Bev Fogtman, who kept track of our inventory.
Standing about five feet two inches, with wavy light brown hair, wire-framed glasses, and a tentative smile, Bev gives the government much more than she is paid. As the repository lead, she manages Little Alaska, Little Siberia, and many other refrigerators and freezers. When the refrigerators and freezers break down in the middle of the night, poor Bev fields a late-night call from the security guards—usually around 3:00 a.m. Then she schleps into the institute, puts on a heavy winter coat, and transfers everything from the broken freezer into a new one.
Fortunately, it wasn’t too late in the evening when I called Bev and verified the latest numbers on my spreadsheet with what she had.
The phone remained quiet after that, so I decided to go to bed, in case I wouldn’t get the chance later.
Around 2:30 in the morning, I stumbled out of bed and down the hall into my home office to answer the urgently ringing phone.
“I need you to pack and ship one hundred doses of antitoxin to Japan emergently,” the deputy commander said.
Excuse me?! I was shocked. Did I hear that correctly? Most botulism clusters are small, with a few victims. 100 people? 100 doses? What the hell was going on?
The deputy commander couldn’t give me the full scoop over the phone—a matter of national security. At this point it didn’t matter. I knew I had to drive back to the institute. I told him it wasn’t just a matter of shipping the antitoxin. Our antitoxins were investigational products. They were not licensed. Mounds of paperwork would have to accompany the antitoxin, and someone would have to administer it. I needed to call in some folks.
I asked whether ventilators were available—a potential lifesaving measure for the most severely ill victims. The deputy commander said he would look into it.
The reason for my earlier feeling of visceral unease was confirmed by the time I hung up the phone. This was a disaster.
Someone must have attacked a large population, I thought. But how? Where? Why? Had a terrorist unleashed this in Tokyo, the site of a prior nerve agent attack?
If recognized and treated in time, antitoxin can halt the spread of paralysis but not reverse it. This is not as simple as it may seem because a victim presenting with slurred speech, drooping eyelids, or gagging may lead the physician to misdiagnose him or her as drunk, high on drugs, or mentally disturbed. The wrong treatment might follow. If the patient is discharged home, he or she could be dead by morning.
Like millions of tiny magnets, the botulinum antitoxins circulate in the blood, binding and neutralizing the toxins. The time window to treat someone is short, though, because the toxins enter the nerve cells quickly, and the antitoxins can’t follow them inside. If not administered before the toxins enter the nerves, paralysis ensues.
We had to act quickly. With each passing hour, the numbers of victims could be mounting and their illness severity worsening.
I called Bev again and woke her up. I told her I needed her to come in to USAMRIID to help get a delivery ready, but I didn’t tell her the destination or purpose.
My wife was still sleeping. All I could whisper to her before I rushed off was that I had to go back to the institute for an emergency. She was used to it and knew not to ask questions.
I threw on some clothes and stumbled down the stairs and out to my car. By then it was just after 3:00 a.m.
I held a three-way call with USAMRIID’s deputy commander and commander during my thirty-mile drive up Interstate 270 to Fort Detrick. As we talked, my headlights penetrated the inky-black surroundings and shadowy trees as I left the streetlamps behind and drove north through lonely countryside.
We needed someone to hand-deliver the shipment to Japan and to administer the antitoxin.
At the time I was fighting a severe sinus infection and taking antibiotics. I wanted to go myself, but I shuddered at the thought of a sixteen-hour flight with blocked sinuses. The commander asked me who could go in my place. I had only a couple of other docs in my division with the knowledge and authorization to administer this type of experimental treatment while meeting all the safety requirements of the Food and Drug Administration (FDA). I first suggested Ellen Boudreau, my clinic chief. She had extensive experience giving experimental therapies. We collectively decided, though, that for something this big, a military officer-physician should go.
I had an air force colonel in my division named Carl Lindquist. Carl was an infectious disease doc on loan to USAMRIID for just a year, but he understood investigational products. Soft-spoken, tall, thin, with light brown hair, Carl was my choice. It would take a lot to stress him. Unfortunately, he had just returned that afternoon from a couple of weeks substituting as the infectious disease doc at the Landstuhl Regional Medical Center in Germany. Regardless, we all agreed that Carl was a good choice.
I called Carl at home around 3:30 a.m. I cringed as his wife’s scratchy voice answered the phone, knowing I had awakened her. I heard muffled sounds of movement in the background, and then Carl’s voice came on the line. I had awakened him as well. I briefed him on the situation. After some more muffled sounds as he and his wife conferred, he said, “Okay. I’ll go.” I told him to pack his flight bag, bring his passport, and wear his dog tags, and that I would be in touch later in the morning.
A single incandescent bulb cast an eerie aura over the guard station as I entered USAMRIID’s back entrance and signed in with the night guard. USAMRIID was a ghost town at that hour. I passed by glowing red and green lights and the steady hum of the laboratory air handlers in the dark hallways en route to my office.
The austere cream-colored walls in my office seemed particularly stark at that hour. I sat down at my desk, pulled out a sheet of paper, and started to draft a list of supplies that Carl would need to administer the antitoxin: needles, syringes, intravenous fluids—anything I could think of.
Another colleague of mine, Dr. Judy Pace-Templeton, ran the Regulatory Affairs Division and had schooled me on the nuances of FDA regulations and investigational products. With medium height and mid-length brown hair that fit her no-nonsense attitude perfectly, Judy taught me how to protect my turf in the usual interdepartmental tugs of war when I was a spanking new division chief. We became trusted friends and allies as we supported each other through some of the battles.
On this occasion I realized that I needed Judy’s expertise—and fast. Fortunately, she answered when I called her around 4:30 a.m. The deputy commander had alerted her earlier, and she was already on her way in.
When Judy joined me in my office, we sat on my beat-up white love seat and wracked our brains to finalize the supply list for Carl. Frustrated, I still didn’t know the details of what we were dealing with and why. When I complained to Judy and described to her what I knew, her facial expression changed suddenly from concern to fear.
“My God,” she gasped. “They’ve gotten the president!”
Oh shit, I thought. Suddenly, it all became clear. She had to be right. What else would have pulled us out of bed for these kinds of numbers? This was even worse than anything I could have imagined. Somehow, someone had “slimed” President Bush with bot. He could already be dying. It was up to us to save him.
At the time an Asia-Pacific Economic Cooperation (APEC) summit was being held in Shanghai. The president and his entourage were attending. That was the reason for shipping the antitoxin to Japan. Judy had put two and two together.
Giving an investigational antitoxin was no simple matter. You can’t just line up a bunch of people and hook them up to an IV drip. You must explain what you are giving them, advise them of possible side effects, and have them read and sign a sixteen-plus-page consent form. This might not be so onerous for a research study without time pressure, but when people are scared to death from botulinum intoxication and choking on their own secretions as their paralysis progresses, it is hard to focus. They don’t want to sift through a sixteen-page document; they just want to get an effective treatment and feel reassured that everything will be fine.
At least we already had FDA-approved protocols in place. Although each was the size of a small phone book, over fifty pages long, the protocol provided line-by-line instructions, like a cake recipe, on how to give the antitoxin. We took our supply list and multiplied it to meet the needs of one hundred patients.
Each dose of antitoxin takes hours to give in a hospital with an intravenous pump. That meant we needed a ton of specialized pumps. The deputy commander put me in touch with an air force flight nurse who was tasked with coming up with the needed supplies. I sent her the supply list and requested at least fifty intravenous pumps along with all the other equipment. When I talked to her on the phone, she was not happy.
“Where am I supposed to get fifty iMed pumps?” she asked.
“I don’t know,” I said, but I wanted to scream, How the hell would I know? It’s not my problem. Figure it out and get me what I need. I have enough things to worry about.
We knew of seven types of botulinum toxin–producing bacteria: serotypes A, B, C1/C2, D, E, F, and G. Ordinarily, the CDC would provide antitoxins for botulism, but the CDC kept antitoxins on hand for only three serotypes, A, B, and E, because those serotypes caused the majority of natural disease in humans. The antitoxin must match the toxin to the letter for the treatment to be effective. Like fitting Cinderella’s glass slipper to her foot only, not her stepsister’s, the antitoxin won’t work if you give the wrong one. Sugar water would have the same result. I had discussed potential options with the deputy commander on the phone, but Judy and I had to make a very difficult decision. We had three different antitoxins in USAMRIID’s freezers. In 1990, while planning for the first Gulf War, the DoD worried that Saddam Hussein had developed a biological weapon arsenal, which included botulinum toxins. This was a problem because the enemy will most likely use the biological weapon that we haven’t prepared for. Therefore, the DoD launched a program to develop antitoxins against all seven botulinum toxins.
Fort Detrick has a separate base known as Area B, or “the farm,” a couple of miles away from the main base, where animals were used to make countermeasures or diagnostics. At one point USAMRIID housed horses there to make the botulinum antitoxins. Scientists injected tiny amounts of the seven toxins into a couple of horses over time—just enough to stimulate the horses to make antibodies against the toxins but not enough to make them ill. After all serotypes had been injected into a horse, blood was drawn, and the serum (and the antibodies in it) was separated from the blood cells to produce the antiserum/antitoxin. One horse, named First Flight, produced the early botulinum antitoxins. A memorial stone now rests in front of USAMRIID dedicated to him.
We wanted to select the best product to treat and protect the president and his entourage. One downside with the First Flight product was that the relative amounts of each antitoxin varied because the antibodies produced in one horse against the seven toxin components varied. It’s like having a factory producing seven different widgets, but the workers spend different amounts of time making each widget. At the end of the day, they have produced different quantities of each widget. So a second product was developed to overcome that challenge. Only one toxin was injected into one horse. Each horse “factory” then produced a single antitoxin. The manufacturer then blended the individual antitoxins from multiple horses to make a combined product with uniform concentrations of all the different antitoxins.
The main problem with both products was their origin in horses, because they risked causing an anaphylactic reaction or serum sickness in people. The manufacturer removed part of the horse antibody to try to make the second product safer. Regardless, Carl would still have to give every patient a small test dose and watch for a reaction before giving the full treatment. Then he would have to monitor the patients very closely for several hours during the intravenous infusion. Normally, a single nurse would be dedicated to a single patient to give this type of treatment in an ICU. Monitoring one person was difficult. Monitoring one hundred people was impossible. Carl would have to enlist local assistance to help him once on the ground. The last thing we wanted was to treat someone for botulism, only to have the person die from an anaphylactic reaction.
We had a third product: Human Botulinum Immune Globulin (HBIG), made by drawing blood and separating the serum from volunteers who had previously received the botulinum toxoid vaccine. The human product had the advantages of a lower risk of allergic reactions and it was easier to administer—especially to large numbers of people—because it’s derived from humans, not horses. However, there was one major downside: it only covered five of the bot serotypes, A through E, not all seven.
In the dark morning hours, Judy and I wrestled with the decision of which product to pack and ship. There was no perfect solution. Sitting in that lonely office in hushed silence, with the clock ticking on the wall toward our impending deadline, we felt the gravity of the situation weighing on us. If we made the wrong call, victims would receive the wrong treatment. Some might die—possibly even the president. We had no way to know which toxin may have been used as a weapon. We weighed all the factors we knew and took our best shot. We went with the human product.
By this time Bev Fogtman and her assistant had arrived. They tag-teamed counting all the vials and verifying the correct lot numbers. They packed up the antitoxin while Judy and I worked on the supply list and notified the army’s regulatory person on call. Fortunately, Bev had years of experience packing special vaccines or treatments. She had shipped lifesaving bot antitoxin to Ohio for an infant dying of the rare type F botulism, when the standard antitoxins didn’t work. She had also assisted on a prior shipment of Rift Valley fever vaccine to Saudi Arabia during a massive outbreak there.
Like building a small igloo, Bev chose the right balance of cold packs and insulation to maintain the cold temperature during shipment for a day or more. She had to figure in not only transit time but also other delays, like customs approvals. It would be a disaster to pack something incorrectly only to learn upon arrival twenty-four hours later that the product had thawed and was worthless. Bev lined the bottom of an insulated container with dry ice, then arrayed several layers of brick-sized blocks containing frozen liquid on top of the dry ice. Once she placed the antitoxin vials inside the container, she finished off with a few more layers of blocks and then a sponge to keep the cold in.
To ensure verification that the cold temperature had remained steady during shipment, the DoD used something called a TempTale, a temperature sensor about the size of a small cell phone with a short wire tail, that was placed inside the storage container during shipment. When Bev pushes a red button on the TempTale’s face to turn it on, a small screen displays several indicators. A sun shows the sensor is operating. The user can key in desired temperature ranges. When the package arrives at its destination, the recipient checks the display, which will show whether the temperature has remained in the desired cold range during shipment or whether it rose too high and the product may be at risk.
I eventually told Bev what was going on. She later acknowledged that her first thought was, Oh shit.
While Bev packed the product, her assistant busily printed and collated one hundred informed-consent documents for Carl to bring, which amounted to over 1,500 pages.
This all took a couple of hours. Then, when we neared completion, I received another call from the deputy commander: “Increase the shipment to 150 doses.”
My God! What the hell was going on? Things were getting worse by the minute.
Off we scrambled to get more product, pack it up, print over 750 more pages of informed consent documents on our dangerously hot copy machine, expand the supply list, and package it all correctly. We worked tirelessly until the morning light peeked through my window, finally finishing around 6:30 a.m. We didn’t have time to pat ourselves on the back. Carl’s flight was scheduled to leave around 8:00 a.m.
We debated whether to use a police escort. Time was short, but we didn’t want to attract attention. Around 6:45 a.m. I received the approval to do so. Fort Detrick provided a police escort to ferry me with the product seventy miles down the highway to Andrews Air Force base in Washington DC, where Carl would catch his flight. My house was just off the highway en route to Andrews, so I arranged to rendezvous with Carl at my house on the way. It was a good thing we had the escort. Without it we never would have made our appointed arrival time. We hit the usual morning DC gridlock, so the police officer turned on the lights and siren. I was amazed to watch the traffic part in front of us like the Red Sea for Moses. When we entered my neighborhood, I asked the officer to turn off the siren to avoid scaring my neighbors. I rushed inside my home for a moment and ran into my eight-year-old son, who was about to leave for school. He had seen me get out of the police vehicle.
“That’s a police car,” he said in a panicked voice. I reassured him that everything was okay and that I wasn’t under arrest. I still couldn’t share any more with my wife, who was equally concerned.
Our understanding was that a jet would be on the tarmac, being fueled and ready to carry Carl to Japan emergently. When we arrived at the Andrews gate, I assumed the skids had been greased, and we would be whisked through. Not so. Even though we were in a police SUV, we encountered a bit of a hassle. The gate guard finally let us through after we said our plane was fueling and we had an imminent departure.
We arrived at the airfield a little after 8:00 a.m. The next challenge was getting the product through the terminal security. The box loaded with the 150 vials of antitoxin was about three feet cubed—too large to fit through the X-ray scanner. The security guard wanted to open the box. I refused. I couldn’t risk disrupting Bev’s careful packaging.
I described in general terms what was inside: “A special medicine to treat a disease. I can’t let you open it,” I said. “If you do, you could destroy it.”
After some more back and forth, the guard relented and called for a bomb-sniffing dog instead. The dog circled the package a couple of times, sniffed, and fortunately didn’t get excited or sit down. The officer finally gave us the go-ahead to enter the terminal.
Scanning the multiple jets on the flight line, I couldn’t tell which one might be Carl’s. We were the only ones in the empty terminal. I paced a line in the white terminal floor while waiting, waiting, waiting over an hour wondering when he would launch—longer than I thought it should take.
Around 9:50 a.m. Carl’s cell phone went off. He spoke briefly. When he hung up, he said, “Sec Def called it off.”
What?! That was it? The Secretary of Defense called it off?!
In a matter of seconds, the long night’s fiasco ended. Up to that point, I considered the possibility that this could have been a real event, a false alarm, or an exercise. Neither of us knew. We also didn’t know how high up the chain of command this event reached, but now I knew: it had reached at least to the Secretary of Defense.
I didn’t learn the full story until sometime later. This was not a drill.
There are numerous “sniffing devices” arrayed around important sites in Washington DC and strategic locations throughout the country. They suck in high volumes of air and concentrate it for automated tests for biological weapon agents. This sounds great in theory, but in a real-world setting, those devices have problems. The concentration of agent they detect may be higher than the amount needed to infect someone. So they might miss an attack, but people could still get sick. The other, more common problem is that they kick off needlessly for benign organisms that cross-react with the test for a threat agent, causing a “false positive” alarm. The tests are based on antibodies binding to targets on a specific agent. Using the skeleton key analogy again, the key might work in more than one lock.
Judy’s hunch had been correct. One of the “sniffers” at the White House had detected a positive “hit” for botulinum toxin. There was a very real scare that the president and key staff members had been exposed to the toxin just before they left for the Asian summit. Our mission was to ferry the antitoxin to Japan or China to administer to the president’s entourage.
While Judy and I had slogged through assembling the antitoxin shipment, unbeknown to us a USAMRIID diagnostics team had spent the night elsewhere in the building testing the suspicious sample to verify whether the “hit” from the sniffer for botulinum toxin was real.
The best test for bot is a “mouse bioassay.” You line up a bunch of mice, inject them with the suspect sample, then wait. They will end up by morning either “feet up” (dead) with their backs on the bottom of the cage or “feet down” (alive) standing.
After the event I had lunch with the commander where he said that in the early morning hours, probably around the time I left Fort Detrick in the police SUV, he was awakened by a surprise phone call from Attorney General John Ashcroft. While on the phone, suddenly Tom Ridge, director of Homeland Security, piped in. Clearly, he was on a direct line to the White House. This was no minor incident. When he received the test results, the commander told Ashcroft and Ridge that the mice were “feet down.” All clear. Once that information percolated through the different channels, the secretary of defense called off the operation. All this from a false positive sample.
As we discussed the operation later, Judy and I were upset. We had to make a judgment call on the best antitoxin to provide based on limited information. If we had known that our own diagnostics teams were simultaneously running the lab assays, we could have conferred directly with them about whether they suspected one toxin serotype versus another and then selected the product most likely to succeed. Using licensed, rather than investigational products, is so much simpler. Maybe the licensed antitoxin could have been obtained from the CDC, and thus we could have eliminated all the FDA paperwork.
Fortunately, everything ended well, but I shudder to think that the president might have died if we had picked the wrong antitoxin because we lacked a basic piece of information.
Condoleezza Rice describes this event in her memoirs and during an interview with George Stephanopoulos. “We were just a little unnerved,” she said.1
President George W. Bush also writes in his memoir that while at the summit in China, on a video teleconference with a pale Vice President Cheney, the vice president said, “The chances are we’ve all been exposed.” As the president notes, “At the time, the threats were urgent and real.”2
That was the understatement of the century. Having just dealt with anthrax, dealing with bot was certainly feasible. What might be next?
Four years later, in September 2005, during a large antiwar protest on the Capital Mall, near all the major monuments, six automatic air detectors had a positive signal for the “rook,” tularemia, another Chessman. The CDC wasn’t notified for three days. The CDC then notified public health officials three additional days later. The Department of Homeland Security and the CDC took heat for the delayed notification. The sniffers appeared to work correctly, but the agent was probably something occurring naturally in the environment, possibly kicked up by the movement of the marchers, and not from terrorism.3 Fortunately, no illnesses were identified.4 Tularemia can cause severe pneumonia with only a few bacteria, so it is frightening to think what might have happened with such a delay for a real event and the thousands of people in the area at the time. We were fortunate.
The technology and procedures related to use of the sniffers have improved over the last decade, but like anything new, they have their limitations and potential pitfalls.
The botulinum toxin response was just one of many short fuse events that we dealt with in the aftermath of the 9/11 attacks. The following week I met in the White House with one of the physicians to discuss countermeasures. While I was there, he escorted me down into the nuclear fallout bunker underneath the East Wing to store some countermeasures. We walked down a carpeted stairwell, through the massive vault-like door. It was sobering to view the Emergency Operations center where the president and the National Security Council had met during the 9/11 attacks—only six weeks earlier. We went into the small medical room, filled out a log documenting the names and numbers of the medical products I had brought, signed the form, and set the products in the freezer.
This would be the first of several trips I would make to the White House. My Medical Division, our regulatory team, and USAMRIID’s diagnostics team continued to serve a vital role in support of the national response after 9/11. We faced more challenges ahead.