The Anthrax Letters: The Attacks That Shocked America (30 page)

When Connell saw Jessica Mann that morning, they discussed Mann’s work plan. “Today, mainly I’ll be infecting blood samples with anthrax,” Mann said, “and checking time points every 4 hours. I guess I’ll be in and out of the monkey suit for the next 12 hours.” Weeks earlier they had seen the first sample of anthrax-blackened blood. The image remained vivid in Connell’s mind as she told Mann to be careful and not to stick herself. Connell reviewed her own schedule. Speaking as much to herself as to Mann, she said she needed to get over to ICPH for class, back to the medical school to give a noon lecture, then to a meeting with some biodefense researchers. A smile from Mann and Connell concluded, “so let’s ‘talk’ by e-mail tonight.”

Twenty minutes later Connell was standing next to a table in the middle of a small conference room on the second floor of the ICPH. Her 10 o’clock class was about to begin and she was checking that her Power Point projection was in focus. Six graduate students were squeezed around the table. Another 10 were sitting against the wall. They needed no reminding, but Connell began anyway by saying that they would be talking about
Bacillus anthracis
. “What I’d like to do is start with the capsule and the toxin. Here’s a picture of the bacteria under the microscope.”

She clicked on the first slide. Clumps of reddish-purple rectangles were everywhere. The rods looked like pieces of All-Bran cereal connected end-to end. “People call them ‘boxcars’ because they form long chains,” Connell said. She clicked on a second slide. The chains were further magnified into curves and twists that were strangely aesthetic. Connell murmured, “They’re really lovely,” aware of the irony of such a description for something so deadly.

She discussed other bacillus species, including
Bacillus cereus
, a relatively harmless bacterium that anthrax resembles. But the anthrax bacterium possesses a unique cell wall made of a particular sugar. “All virulent
Bacillus anthracis
form this polysaccharide capsule,” she continued. Connell explained the basis of the toxin. “What’s cool about the anthrax toxin is that it has three factors.” Another slide labeled the factors. One was called “protective antigen,” which in effect is the capsule itself. A second was “edema factor,” which, as the name suggests, is a protein that induces fluid to accumulate in the area of infection. Third is “lethal factor,” another protein.

Distinctive genes are responsible for the synthesis of each factor. But the genetic expression of all three is necessary for the toxic effect. “You need all three toxins to cause lethality of a macrophage,” Connell said, referring to the body’s cell that ordinarily engulfs and destroys a foreign invader.

She inserted a comment about anthrax as a bioweapon. “So it is the toxin that kills. We don’t care about the bacteria, just the toxin.” She noted that biological agents on the skin are unlikely to cause problems unless they land on a scratch or other opening. Yet during some recent anthrax threats, people were made to undergo vigorous scrubbing. “That is the wrong thing to do because you can abrade and open the skin,” Connell said.

Dr. Connell spoke quickly, enthusiastically. She paused intermittently to allow her listeners a moment to absorb her point. The result was speech delivered in packets bracketed by cushions of silence. Her voice, though soft, sounded eager, as if coming from someone on the edge of a chair. Connell’s style seemed just what her students appreciate. As a tribute, she has repeatedly won the “Golden Apple,” an award designated by the school’s graduate students for excellent teaching.

A student in sandals who was sitting across the table raised his hand. He said he had read that anthrax growth is enhanced by contact with carbon dioxide. “Does that mean that the effect of inhaled anthrax is made worse because of carbon dioxide in the lungs?” he asked. Connell mulls over the question, one that she had not thought about before. “I guess there might be pockets of carbon dioxide where that could happen,” she said, acknowledging uncertainty. She said she’d research the question and have an answer for him next week.

During the last minutes of the class, Connell asked if everyone had read the paper she had assigned. Heads nodded in the affirmative. “So let’s talk about it,” Connell said. Titled “A Bacteriolytic Agent that Detects and Kills
Bacillus anthracis
,” it had appeared two months earlier in
Nature
and described a study led by Vincent Fischetti of Rockefeller University in New York City. “Who can tell me what a phage is?” Connell asked. Hands shot up, and Connell pointed to a young woman in a brown sweater. Her answer, delivered with a slight Spanish accent, was brief and on the mark: “It’s a virus that infects bacteria.” “Exactly,” Connell said. “The ‘bacteriolytic agent’ referred to in the title is an enzyme of a particular virus called gamma phage virus.”

Mention of gamma phage harks back to the laboratory test that Phil Lee had performed the previous year to confirm the presence of anthrax in Bob Stevens. Now, Fischetti had isolated the active ingredient of that virus. The article described how the ingredient kills the anthrax bacillus by “lysing” it. “Lysis,” Connell explained, “means that the bacterial cells are blowing apart and everything is leaking out.” Fischetti and his coauthors concluded that the isolated ingredient could also be “exploited as a rapid method for the identification of
B. anthracis
.” The sentence resonated for Connell. Although she did not say so in class, the central effort of her own experiments with biowarfare agents is to develop a method of rapid identification.

At 11:40 Connell ended the class, apologizing that she could not linger for questions. She gathered her notes and computer into her briefcase. It was raining, so she would be driving the half mile back to the medical school for her noon lecture there. She donned a dark gray raincoat and plunked an old brown fedora on her head. “It was my grandfather’s. I took it after he died in 1978, and I wear it in the rain,” she told me. Her sartorial selection seemed at once a gesture of sentimentality and a carryover of 1960s nonconformity. As she scurried across the street to the parking lot, Connell’s seamless movements appeared more like the glide of a hydroplane than a sequence of footsteps.

In the ground-floor kiosk at the medical school, Connell purchased a dollar bottle of spring water, and rushed up a dozen steps to lecture hall 610. She would speak from a pit, looking upward toward seven ascending rows of seats. Coarse cream-colored bricks lined the walls. The lecture was open to the medical faculty, and a dozen men and women in white coats were already seated. Another 20 trickled in as Connell prepared her Power Point. “Today I’m going to talk about two things—some of my activities with TB in the lab and then a bit on the Center for BioDefense.” Again, Connell spoke in enthusiastic spurts. Her curly brown hair, an inch short of her shoulder, bobbed when she turned to the screen and back to her audience. “So here is a graph showing the time that it takes for the metabolism of arginine within the mycobacterium cell.”

After 45 minutes, Connell took a few questions and then briefly described the Center for BioDefense. “It was established in 1999, as many of you know, and we are continuing to get great support.” She summarized a few of the center’s projects, including her own, and took the last question at 1:10 p.m. From there she moved quickly, one flight down the escalator, and a right turn. A few hundred feet and Connell entered the cafeteria. Ten minutes late, she joined nine people in a back room off the cafeteria for a luncheon meeting. They were research scientists, all associated with the Center for BioDefense. The scientists represented a range of specialties—David Alland, thin with a young face, is involved in tuberculosis diagnostics. Elizabeth Raveche, tall and blond, studies laboratory medicine with animal models.

Connell apologized for being late. David Perlin, who heads the Public Health Research Institute, which is associated with UMDNJ, answered, “That’s okay, Nancy. We wouldn’t start without you.” He smiled, joined by a few others, knowing that Connell was supposed to chair the discussion. “Let’s order the food first,” a voice said. A waitress announced that the grilled chicken and vegetables were especially good. “I’ll have that,” Connell said, “and a Diet Coke.” Each person placed his order.

“So what projects do we want to put forward?” Connell asked. The National Institutes of Health is providing $10 million for research institutions in the New York-New Jersey area, she said. UMDNJ and the Center for BioDefense would like to get a bite of at least a half million. Someone suggested, “We’d want to start by infecting small animals with select bioagents, work up to larger animals, then to natural hosts.” To which Raveche responded, “Well, I think we ought to consider transporting human cells into mice. Diagnostic and vaccine testing then could be done in one model.”

As the discussion continued, Perlin suddenly got everyone’s interest. “We ought to be trying to build a BSL-4 laboratory.” He said the first few million could be available from current funds, but for additional funding “we need political support.” It was clear that he had been thinking about the matter. He elaborated:

A few people mentioned contacts they had who might be helpful and the need to get one of the university’s vice presidents behind the effort. Perlin created a large vision:

As the discussion continued, people at the table expressed enthusiasm about Perlin’s ideas. No one questioned whether the university should be seeking a BSL-4 lab but just how it could be done. Still, scientists elsewhere had begun to voice concerns about the growing number of laboratories equipped to do work with warfare agents. Richard Ebright, a Rutgers biochemist, worried about level-3 as well as level-4 laboratories. “It is difficult to conceive of scenarios,” he said, “under which increasing the number of persons with access to, and training with, agents such as
Bacillus anthracis
,
Yersinia pestis
, and
Francisella tularensis
would enhance—rather than degrade—national security.”

Nancy Connell had been quiet during the discussion about seeking a BSL-4 lab. Months earlier she had signed a letter with Ebright to
Nature
magazine that favored limiting the number of institutions with access to bioweapons agents. “I’m aware of Ebright’s concerns,” she told me after. “We still have to figure out the right balance.” Connell filled the rest of the day with a visit to her postdoc and two graduate students who were conducting tuberculosis experiments. They were at the laboratory at the ICPH, where they had access to the new BSL-3 facility just completed there. She thought about Perlin and Ebright, both decent people but with such different perspectives. She contemplated how far she had come in her own thinking.

She burst into laughter. “Who’d ever have thought that my best friends would be lieutenant colonels?”

Nancy Connell, like many others in science and in law enforcement, intelligence, and public health, is in a contest against bioterrorism. They are racing to protect Americans from the kind of anthrax horror the country experienced in 2001. The result of Connell’s research, like that of hundreds of other current bioterrorism-related science projects, may not be known for some time. But the fact of her engagement reflects the altered mind-set shared across the country. Connell still feels the tug of her social activist roots. But she is no less drawn to the challenges peculiar to these times.

The challenge presented by the anthrax letters was novel in many ways, though not all. The letters were not the first anthrax threats by mail. Prior to the actual anthrax incidents, there had been hundreds of hoaxes. Commonly, a letter would contain powder and a message that the reader had been exposed to anthrax. While all those threats proved to be false alarms, for some recipients the experience had been terrifying.