On October 9, 2001, two days after the phone call with John Ezzell and the FBI, I was back into my normal daily routine of running the Medicine Division at USAMRIID. I had just returned from a meeting and found a yellow phone-message slip on my desk.
Mark,
Tom Brokaw called. Please call him back.
He is expecting your call.
I reread the note before it registered. Wait a second . . . the Tom Brokaw? Shit, I thought. What could he want?
My mind raced through recent events that he might be calling about but came up blank. Having Tom Brokaw call wasn’t too unusual, I suppose, because USAMRIID attracted the news media like flies to honey. After all Diane Sawyer had interviewed our former USAMRIID commander, Colonel David Franz, about biowarfare, inside the Slammer, no less. Novelist Robin Cook spent a day with my Operational Medicine colleagues before publishing Vector, his medical thriller about anthrax. At the time Tom Brokaw was the anchor for the NBC Nightly News and one of the most powerful men in the media, so I admit to feeling a bit nervous about calling him, but I was curious to know why he had called. Before I picked up the phone, though, I wanted to ensure I had the right people in the room with me to handle his issue.
I grabbed the slip of paper and a note pad and marched down the hall toward the USAMRIID headquarters. On the way I ran into Art Anderson, an army pathologist with a soft voice and a relaxed manner. As head of our clinical laboratory and Institutional Review Board (IRB), Art’s knowledge would be invaluable if Brokaw wanted to ask us a diagnostics-related question. I recruited Art to join me. Upon arrival in the headquarters, I also pulled in our operations officer (a veterinarian), along with the deputy commander, a virologist, for the call. The commander was away for the afternoon, so we huddled in his office around the conference phone on the large oval table.
Brokaw answered the phone himself with his unmistakable loud, authoritative voice and explained the situation. On September 25 one of his assistants at NBC, thirty-eight-year-old Erin O’Connor, had opened a suspicious envelope addressed to Brokaw with powder inside and threatening words about a biohazard in the enclosed letter. Some testing done by local law enforcement on the powder was negative for anthrax. Since then O’Connor had been having problems with a skin lesion on her left shoulder.
After a few minutes, Brokaw passed the phone off to O’Conner. She explained that three days after opening the letter, she had noted a sore on the front of her chest near her collarbone, like a mosquito bite. Over the weekend of the twenty-ninth, she became ill with a fever, and the skin lesion progressed to a black rash an inch and a half long “like something [had] gouged it out.” She saw her primary care doc and then a tropical medicine specialist, who told her it looked like anthrax. She started taking the antibiotic ciprofloxacin on October 1. The lesion and fever had improved by this time, and she had a residual black scab.
The list of possible causes of a black scab is long, with culprits ranging from bacterial infections on the high threat list, like tularemia and plague, to more common viruses, mycobacteria (tuberculosis-like organisms), parasites, and rickettsia (e.g., typhus), but she had no risks for any of those uncommon agents. Although anthrax was possible, since the letter had tested negative that seemed less likely. So we raised the possibility of more common things, including an allergic skin reaction, a chemical irritant, or a spider bite, in addition to anthrax.
I asked O’Connor about potential exposures, including hobbies that could have led to the lesion—whether she gardened, had any recent insect bites, cuts, contact with fish, but making any conclusion based on a phone call is a challenge without seeing the lesion or the patient. Like buying a house without ever seeing it, there is usually a surprise, and it’s rarely positive. We didn’t have the convenience then of easily taking and texting photos.
A dermatologist was seeing O’Conner now and planned to take biopsies. He wanted to send us a specimen.1 Although O’Conner had no ties to the military, Brokaw was very persuasive, so we agreed to accept a specimen to test. We told him how to send it to our Special Pathogens Lab, which linked in with the U.S. National Laboratory Response Network.
Art Anderson asked for the skin biopsy specimen to be shipped fresh on wet ice, so he could test it with different methods, including trying to grow anthrax. Instead, it arrived the next day bathed in the chemical formalin. This presented a challenge. Formalin is great for preserving tissue, but it would kill any live bacteria, so we couldn’t grow anything. The other option would be to test with PCR (polymerase chain reaction), a method to amplify very tiny amounts of DNA to a level high enough for detection. Unfortunately, testing PCR on formalin-treated tissues was not routine, so the chief of our Diagnostics Division didn’t want to use an unvalidated test and risk making the wrong call. Therefore, Art made thin slices of the skin tissue and stained them with routine stains and one designed specifically for anthrax. The special “immunohistochemistry” staining method for anthrax was developed by our own special pathogens chief, John Ezzell. It used antibodies to bind to certain proteins on the anthrax bacterial cell wall—like a key fitting in a lock. The antibodies are tied to a dye or something that fluoresces for easy identification under the microscope. As with any lab test, it wasn’t foolproof. The antibodies did not necessarily bind only to anthrax. They could cross-react with other environmental bacteria—like having a skeleton key that unlocks a specific lock but also other, similar locks.
Art reviewed the samples under the microscope but didn’t see any features of anthrax, even though the positive and negative controls he had used during the test performed well. Instead, it had the features of an allergic reaction or a spider bite. It was possible that he just didn’t get the best piece of skin to test. A diagnostic test performs well only with a good patient sample. Anthrax dies very quickly once someone starts antibiotics, and O’Connor had been on antibiotics for about a week. The chance of finding intact bacteria in the wound at the time was like finding a needle in a haystack. Art’s conclusion: negative for anthrax.
Brokaw had mentioned during the phone call that they also planned to send a biopsy specimen to the CDC, but they had not yet reached anyone. A couple of days later, the CDC made the diagnosis of cutaneous anthrax.
Because our sample was negative, Art worried that the CDC had jumped the gun. They had used the same test Art used. Art knew the CDC colleague who made the diagnosis, so they conferred, and he asked him to send the microscope slides for his review.
It turns out that, of the two biopsy sites from Erin O’Conner, the CDC had probably received the “better” sample closer to the edge of the infection site, which explained the differing results from our two institutions. I have looked at the biopsy specimens with Art, and I can see why making the diagnosis was difficult—there were some bacteria on the CDC sample, but they were very scarce and certainly didn’t look like anthrax. The CDC team members made the correct diagnosis, but they made a difficult call based on a suboptimal specimen.
Lawrence Altman, a medical writer at the New York Times, noted that even the CDC director tried to hedge a bit on the diagnosis, telling New York mayor Rudy Giuliani that they made the anthrax diagnosis with “a high degree of probability.” The mayor wanted something more definitive. “Is it anthrax or is it not?” [CDC director] Dr. Jeffrey Koplan responded, “Yes.”2
A couple of days after the Brokaw phone call, Art showed me a photo of O’Connor’s lesion that the New York City Department of Health had sent him. It showed a rough, narrow, black scab (eschar), probably two inches long by a half inch wide on her front left shoulder near her collar bone.
“Shit,” I said when I saw it. “That’s anthrax.” I wished I could have seen it before, at the time of our phone call.
We didn’t have the benefit of hindsight. The stampede of zebras had arrived. It was no longer a theoretical possibility: we were under attack. But at the time, we didn’t know the extent or what was to come . . . that the criminal had mailed multiple anthrax-contaminated letters targeting media personnel and politicians.
The letter to Tom Brokaw that Erin O’Connor opened was postmarked September 18, seven days after 9/11, and mailed from Trenton, New Jersey—the same date and postmark of a letter sent to the New York Post and probably around the same time as the one to Robert Stevens at the American Media building in Florida. The letter contained a threatening message, handwritten and photocopied:
09–11–01
THIS IS NEXT
TAKE PENACILIN NOW
DEATH TO AMERICA
DEATH TO ISRAEL
ALLAH IS GREAT
By October 11 a third employee who opened mail at the American Media building in Florida tested positive. An intern who worked with O’Connor in New York developed anthrax skin lesions on her face, and a seven-month old boy who had visited a different headquarters for ABC News in New York the week before also developed a black skin lesion on his elbow. He was treated for a presumed spider bite until a blood test showed he had anthrax.
On October 13 the national news blew up when O’Connor’s anthrax diagnosis was reported in the media. Anthrax was no longer isolated to Florida. Hundreds of New Yorkers sought medical care. The U.S. Postal service advised people not to open suspicious packages.
There was a national run on ciprofloxacin (Cipro), an antibiotic commonly used to treat anthrax. Calls to USAMRIID’s hotline skyrocketed. Operational Medicine Division Chief Scott Stanek received a call from a man who asked, “What do I need to tell my doctor I have to make him give me Cipro?” Scott refused to answer, saying, “That’s unethical.”
Shortly before 9/11 the biodefense containment laboratory in Canada had conducted a research study testing how quickly spores like anthrax could spread from a room where a letter is opened.3 The results were shocking: within forty-eight seconds, spores fled the room and crossed the hallway to an opposite room. Within ninety-six seconds they flew into rooms five doors down the hallway. No one could have predicted we were about to experience a real-life validation of the Canadian experiment at the seat of our government.
On October 15 a staff member in Senate majority leader Tom Daschle’s sixth-floor office opened another letter and spilled the powder that was inside, contaminating offices and the ventilation system in the Hart Senate Office Building. Immediately concerned that the powder could be anthrax, the staff member notified the Capitol Hill police, who arrived minutes later. Unfortunately, they did not put on protective equipment until they were inside the office. Anthrax spores landed in the noses of all eighteen people on the same floor of the Daschle office, which included the first responders. The spores floated down one floor through a stairwell in the Daschle office, where seven more workers later also tested positive. Two others in the neighboring sixth floor office of Senator Russ Feingold also tested positive.4
The FBI brought the Daschle letter in a plastic bag to our Special Pathogens Lab for testing. Wearing scrubs and gloves, John Ezzell took the letter first to the BSL-2 Special Pathogens Lab and then into Bacteriology Suite 3 (B3), a Biosafety Level 3 (BSL-3) containment laboratory.5 He slid the letter slowly out of the envelope inside a biosafety cabinet, his hands moving behind a pane of glass and a curtain of air designed to protect the handler. A fine powder wafted up off the letter, swirling in the air waves, like a genie escaping from a bottle.
John had worked in the laboratory for decades. He recognized immediately the danger of this substance, and it scared him. Afraid he might have inhaled some spores, he shoved the letter back in the envelope, hurriedly flushed his nostrils with bleach, because he feared he might have inhaled some spores, and left the lab in a panic. He hustled straight to our clinic looking for me. Scott Stanek saw him in the hall and recognized the worry on his face, different from his usual friendly demeanor. Denise Clizbe, a nurse who had a bird’s-eye view of the main clinic corridor from her office next to the nurses’ station, saw John rounding the corner into the clinic. She recalled, “He was white as a sheet, and he looked like he’d seen a ghost. That was strange for him. He was usually pretty calm.” I wasn’t in the building when he showed up, so one of my docs treated him with antibiotics for possible exposure to anthrax. A few days later over lunch, he described to me the indelible image he saw in the swirling powder: “I saw the face of the Devil.”
As the FBI’s lead testing site, USAMRIID immediately ramped up to 24/7 operations, testing thousands of samples from points nationwide. USAMRIID’s diagnostics team was quickly overwhelmed. Jeff Adamovicz, deputy chief of Bacteriology, who sports a long beard splashed with gray, reminiscent of Ulysses S. Grant, said things “quickly spun out of control because of the numbers of samples, advice on sampling, and determining what was and wasn’t Bacillus anthracis.” The army yanked anyone it could from other departments within USAMRIID or other institutes to assist. “They didn’t have enough space for all these people, so they started working in bacteriology’s Biosafety Level 3 lab,” Jeff said. “I’d seen the chaos with the samples coming in—they were coming in the front door, they were coming in the back door, you had people literally bringing stuff in with paper bags, these sort of evidence bags inside, but they were full of holes . . . we gotta get control of this, and I’m afraid they’re gonna contaminate the hallways.”
Hank Heine, a Boy Scout leader and researcher in USAMRIID’s Bacteriology Division, with a full graying beard, wire-framed glasses, and an outdoorsman’s look, got a call from his division chief at 7:55 p.m. that evening to report to the division office. There the chief told him, “Well, you know what’s going on today, you’ve seen the news . . . well the letter’s here. You need to go back into [building] 1412, get some of that, grow it up, and you need to run all the antibiotic susceptibilities on it.” Hank did as he was told. He needed to get the bacteria in the letter down to the individual spore level, which would grow into individual colonies of organisms that he could later test against antibiotics. Using standard microbiology methods, Hank spent the next seventy hours back in the lab growing anthrax from the letter and running the susceptibility tests.
Hank selected agar infused with sheep blood, which gives the agar a blood-red color, because anthrax likes to grow quickly on it. “The stuff was like baby powder,” he said. As Hank inserted a thin plastic probe with a loop on the end into a plastic baggie containing the powdered spores from the Daschle letter, he was amazed to see the spores jump up and cling to the probe like metal filings to a magnet. Next, he dabbed the loop on an agar plate and streaked a line of spores across one quadrant of the circular red plate, like an artist drawing a brush across a canvas. Taking a new probe, he streaked through the original line and made another line. He repeated this several times, so that with each successive streak, the number of spores would be diluted down to individual colonies once the bacterial growth appeared later. Then he put the plates in an incubator and waited for the bacteria to grow.
Hank found himself suddenly in high demand, as calls came into his lab from others in the institute, our commanding general, and congressional offices. This was not surprising because what his tests showed would determine the best antibiotics to treat anyone with who had been exposed to the letters.
The next day, the Diagnostics Division chief called me up to his office. He was concerned about the high volume of incoming samples and the potential risk to his personnel from them, especially from the Daschle letter. We sat down at his desk, and he took out a personnel list and yellow highlighter. His hands shook as he drew the highlighter across the names of nineteen people working in the lab whom he was worried about.
I notified my medical team that we needed to get eyes on these workers urgently to evaluate their risk of exposure. We phoned each one, called them down to the clinic, and swabbed their noses to test for anthrax. We started eleven on antibiotics, but we urgently needed Hank’s bacterial susceptibility results to know whether we had picked the right antibiotics. We also evaluated everyone’s anthrax vaccine schedule and boosted some. The threat was real, so we couldn’t be too careful.
When he had first received the letter sample for testing, Hank immediately dove in and thought “it had to be antibiotic resistant.” Over the next day, as the usual shimmering gray/white colonies of anthrax bacteria grew and spread out across the surface of the red agar plates, he noticed that some of the colonies looked a little different. They had a less shiny appearance when he held the plate at an angle to the light. Given time the colonies took on a flatter, yellowish appearance, sometimes creating a halo clear zone around the colonies as they burst the sheep red blood cells that were mixed into the agar. Hank assumed the different colony morphologies (“morphs”) to be bacterial contaminants.
On October 16 a bacteriology technician who was also culturing the Daschle letter samples in the neighboring lab, called him over. “Hank, take a look at this,” she said. “What do you see?” Similar to Hank’s specimens, some of the colonies on the plates looked different. “It looks like a bunch of contaminants,” Hank said. “Well, they’re all testing out to be B. anthracis,” she replied.
So now it looked like the letter may have contained different anthrax bacterial strains causing the different morphologies. The technician sent photos of the “morphs” to Pat Worsham, who was the chief of the Genetics and Physiology Branch of the Bacteriology Division at the time. Pat has medium brown hair and blue eyes. Her reading glasses attached to a chain usually sit on the top of her head, which combined with her sandals give her the look of a librarian. Pat had published a paper on different colony morphologies made by “oligosporogenic strains” as part of her work developing weakened strains of Bacillus anthracis that might be used to produce anthrax vaccines. She recognized that the spores found in the anthrax letters were a mixed culture. “Logically,” she said, “it would make sense that that might be some sort of signature,” and that an “unusual mix of organisms might be useful.” The significance of that finding would not be apparent for another two years, but it would lead to a breakthrough in the FBI’s case.
On October 17 Hank dropped by my office to tell me the results of his susceptibility testing. The anthrax isolate had a “normal” pattern, susceptible to common antibiotics, including penicillin, doxycycline, clindamycin, and ciprofloxacin—similar to what would be expected from an anthrax organism found in nature. “That bug was a wimp,” Hank quipped later. “That was a big relief on everybody’s part,” he reflected, “because at the time, at least we weren’t dealing with something that had been genetically manipulated.” I was definitely relieved to hear this because the standard antibiotics we had already used to treat our personnel, ciprofloxacin and doxycycline, would still be effective.
None of the nasal swab tests on our personnel came back positive. We later reduced the number of them on antibiotics based on additional risk assessment.
Unfortunately, just because something can be treated doesn’t mean it is not dangerous. Additional investigation determined that the anthrax spores in the letters were the Ames strain—a very potent strain selected for testing possible vaccines because of its deadly properties. The Ames strain was isolated from a cow by a lab in Texas in 1981, but it was named after the town of Ames, Iowa, instead because when a USAMRIID scientist first received the strain from a U.S. Department of Agriculture (USDA) lab, he mistook its origin and named it based on the Iowa return address on the package it came in.
When Jeff Adamovicz, Bacteriology Division deputy chief, received another envelope for analysis inside a plastic ziplock baggie, he realized immediately how dangerous the substance inside the envelope was and that it had been engineered to be that way. “We were trying to work out a concentration of the spores,” he said, “so we had to be able to get some of the spores out of there, get weights, and then figure out what the concentration was,” but the spores were “so energetic that you couldn’t even get them to settle in the baggie.” He didn’t want to open the baggie in the hood because he worried that the spores “would fly out of the bag” and his team could be exposed, even though they wore powered air purifying respirators (PAPRs) to protect their airways. He came up with the idea of trapping the spores in a corner of the baggie, heat sealing that corner, then injecting some water into the baggie so they could extract the spores safely.
On October 17 the FBI released pictures of the Brokaw and Daschle letters. Not surprisingly, based on USAMRIID’s preliminary evaluations, the New York Times reported that the Daschle letter anthrax was “pure and highly refined, consisting of particles so tiny that they could spread through the air without detection.” The letters contained billions of spores in approximately two grams in each letter and “could have been made by an expert capable of producing large amounts of it.” The physician for the U.S. Capitol indicated that officials would “draw up the net as widely as possible and err on the conservative side and test and treat.”6 Eventually, 625 were identified for prolonged antibiotic prophylaxis.7
Next to our main clinic corridor, we had a parallel second corridor, called the “Project Ward,” that we used as an inpatient ward for research. The entire ward could be sealed off as a BSL-3 hospital facility, and research volunteers lived there for up to two weeks for testing of vaccines made from live viruses or bacteria. This system ensured no risk to the community and the ability to monitor the research subjects closely for side effects. We had a full kitchen attached to the ward to feed the research participants.
John Ezzell confronted me in the Medical Division hallway with a highly irregular request. “I’ve got the FBI here in the kitchen,” he said. “They want to test some letters in the oven.” “Are you kidding me?” I was floored. “Very soon the American public will demand to know what to do with their mail,” John said. “The FBI is trying to figure out what to tell them.”
John had filled letters with spores of an environmental organism, Bacillus globigii, to be tested as a surrogate for the anthrax bacteria, Bacillus anthracis. He needed my permission to conduct a scientific experiment: to bake the letters at different temperatures and times in our commercial oven to find an appropriate setting that would kill anthrax spores without setting the letters on fire. The results of the experiment could be used to inform the American public how to decontaminate their mail safely. They had already determined that a microwave would ignite the envelope’s glue. We have a saying in the military that “no good deed goes unpunished.” Though I envisioned my military career ending—if something went wrong, I might get burned—I agreed because it was worth a shot if we could generate something useful for the country. I hoped that focusing on the greater benefit would be viewed favorably in hindsight.
Throughout this frightening anthrax scare, I was just as paranoid as the next person. My wife banished me to our garage to open our mail while I wore a mask. One night I awoke with horrible left-forehead sinus pain, worse than anything I had ever felt. The next morning I blew my nose, and pure blood came out. Anthrax causes local bleeding and swelling.
Did I get some anthrax spores up my nose? I wondered.
I’ll never know. I resisted the urge to swab my own nose, but I felt some reassurance that if I had been exposed, I should have some protection from my prior anthrax vaccinations. But even knowing that did not completely put me at ease. Fortunately, the pain subsided over the next couple of days.
Sometimes, in the heat of the moment, while we are dealing with the routine daily work challenges, it is hard to recognize the significance of the events occurring in real time. When I received that first phone call at church from John Ezzell on October 7, 2001, and the Brokaw phone call two days later, none of us could have predicted we stood on the front lines of a national crisis that would challenge multiple levels of the government and the medical community. In retrospect Erin O’Connor’s cutaneous anthrax case turned out to be one of the earliest identified during the 2001 anthrax attacks—a sentinel for the tragedy and the twenty-two total cases of anthrax that would occur, split evenly between cutaneous and inhalational cases. Five inhalational victims would die. We now know that the perpetrator mailed at least five contaminated letters on two occasions.8 The initial wave included letters sent to the American Media building in Florida, NBC News, and the New York Post. The two sent on the day of our phone call with Tom Brokaw went to Senators Tom Daschle and Patrick Leahy.
The medical system is resilient, though. Eventually, as the news about the letters hit the airwaves, some anthrax cases were recognized, and some patients received lifesaving treatment in time to make a difference. Unfortunately, this familiar delay in recognition repeats itself with every new disease. We used to think of inhalational anthrax as a death sentence. We now know that if we recognize and treat it early, patients will survive. Six of the eleven inhalational cases survived.
The tragedy of the anthrax letters nationally and their long-standing impact on USAMRIID had just begun. We would remain in the national spotlight, for better or worse, for many years.
Years later Tom Brokaw testified before the Commission on the Prevention of WMD (Weapons of Mass Destruction) Proliferation and Terrorism that when he called experts at the army’s biodefense lab, they told him that Erin O’Connor’s lesion was a spider bite. I was disappointed to hear this, and it points to a fundamental misunderstanding of the limits of a phone conversation. All we could do on the phone with such a “curbside” consult was to render a quick opinion. We gave Brokaw a “differential diagnosis,” a couple of possibilities based on the information he and O’Connor had given us: spider bite, anthrax, allergic reaction, and so on. Perhaps we weren’t clear about that at the time, but we did take his concerns seriously, which is why we agreed to evaluate the biopsy specimen. Ideally, we should have been able to see the patient in person immediately after the call, where a full history, examination, and laboratory tests could have been done, but she was in New York and we were in Washington DC. Hindsight is always 20/20, especially in such a rapidly evolving situation.
Only six months into my tenure as the Medical Division chief, I was certainly getting the initiation in biodefense that I had asked for, but I didn’t realize it would be so hard. Some days I would reflect on the simplicity of my earlier career, when all I had to do was take care of my patients. But I wouldn’t trade the opportunity to be at the forefront of preventing further tragedy during nationally significant events. Queen Anthrax outmaneuvered us on this one at first, but that’s why she is the “queen.” Some quick action by a lot of people reduced the potential national impact, but Queen Anthrax would present challenges for us over and over in the years to come.
Just when I thought things would settle down from the anthrax attacks, I should have predicted that things were about to get worse.