Leonard A. Cole: The Anthrax Letters: A Medical Detective Story

When Pat Hallengren arrived at work on August 10, 2002, she noticed that the middle mailbox was missing. It was the one she had always used. For as long as she could remember, it had stood between two other receptacles outside her window in the American Express Travel office in Princeton, New Jersey.

During the late hours of the previous night, postal authorities had removed the box. Before long, word spread about the reason, and local curiosity turned to horror. The mailbox was found to have contained anthrax spores. When Pat heard this, her first thoughts were about her mailman, Mario. "I really wasn't concerned for myself. I mean, I just put mail in the box, but Mario had to take it out." Her worry was understandable.

Anthrax bacteria are as murderous as South American flesh-eating ants. An army of ants, traveling in the millions, can decimate an immobilized individual by devouring his flesh layer by layer. Death is gradual and agonizing. Anthrax bacilli do to the body from within what the ants do from without. They attack everywhere, shutting down and destroying the body’s functions from top to bottom. The organisms continue to multiply and swarm until there is nothing left for them to feed on. In two or three days, a few thousand bacilli may become trillions. At the time of death, as much as 30 percent of a person’s blood weight may be live bacilli. A microscopic cross section of a blood vessel looks as though it is teeming with worms.

The anthrax bioterrorism attacks the previous fall, in 2001, had been conducted by mail. On October 4, three weeks after the terror of September 11, a Florida man was diagnosed with inhalation anthrax. His death the next day became the first known fatality ever caused by bioterrorism in the United States. During the following weeks, more people were diagnosed with inhalation anthrax as well as with the less dangerous cutaneous, or skin, form of the disease.

Almost all the cases were traced to spores of Bacillus anthracis that had been placed in letters. Perhaps a half-dozen letters containing a quantity of powder equivalent in volume to a handful of aspirin tablets had paralyzed much of America. During the fall 2001 scare, congressional sessions were suspended and the Supreme Court was evacuated. Infected mail disrupted television studios and newspaper offices. People everywhere were afraid to open mail.

Four of the anthrax letters were later found and all were postmarked "Trenton, NJ." That was the imprint made at the large postal sorting and distribution center on Route 130 in Hamilton Township, ten miles from Princeton. Ten months after the attacks, when Pat Hallengren’s favorite mailbox had been removed, mailboxes that served the Hamilton facility were belatedly being tested for anthrax. In the first week of August, investigators swabbed 561 drop-boxes and delivered the cotton tips to state laboratories. Only that one mailbox, on Nassau Street near the corner of Bank Street in Princeton, tested positive for anthrax. Could that box, not 30 feet from Pat Hallengren’s desk, have been where the poison letters were deposited?

The mailer of the anthrax letters had not yet been found. But six weeks before the discovery of anthrax spores in the Princeton mailbox, the FBI had identified a microbiologist named Steven Hatfill as a "person of interest."

Days after the middle mailbox was removed, federal agents fanned out through the neighborhood. They showed a picture of a steely, thick-necked man to merchants and patrons up and down Nassau Street. It was Hatfill. "Do you remember seeing this person?" they asked. "I don't recognize him," Pat Hallengren answered, "but I see so many people on this corner." Four doors up from the corner, Shalom Levin, the bearded owner of the Red Onion delicatessen, was ambivalent. "I might have seen him walking around here," he told an FBI official. But perhaps Hatfill's face seemed familiar, he acknowledged, because he had seen it on T.V. In 2003, long after the discovery of anthrax in the Princeton mailbox, the FBI was still searching for the mailer and still considered Hatfill a person of interest.

Between October 4 and November 21, 2001, twenty-two people had been diagnosed with anthrax. Eleven had contracted the cutaneous form and all survived. But among the 11 who became ill from inhaling spores, five died. In subsequent months, with no new cases, national anxiety eased. But the discovery of the contaminated mailbox almost a year later in Princeton drew a torrent of television and newspaper coverage from around the world. Fear had been rekindled.

Concern about anthrax is as old as the Bible. Primarily a disease of animals, it is thought to have been the fifth of the ten biblical plagues visited by God upon the ancient Egyptians for refusing freedom to the Jews. As recounted in Exodus, horses, donkeys, camels, cattle, and sheep were struck “with a very severe pestilence.” After their carcasses were burned, the virulence of the anthrax germs persisted, for the soot caused “boils on man and beast throughout the land of Egypt.”

In recent years, anthrax spores have been deemed among the most likely of biological weapons because they are hardy, long-lived, and, if inhaled, utterly destructive. A victim is unlikely to know he is under attack. As with other biological agents, anthrax germs are odorless and tasteless, and lethal quantities can be so tiny as to go unseen.

Every three seconds or so, a human being inhales and exhales about a pint of air. Each cycle draws in oxygen to fuel the body and releases carbon dioxide, the gaseous waste product. The inhaled air commonly carries with it floating incidentals such as dust, bacteria, and other microscopic particles. If a particle is larger than 5 microns, it is likely to be blocked from reaching deep into the lungs by the respiratory tract’s mucus and filtration hairs. If smaller than one micron, a particle is too small to be retained, and is blown out during exhalation. An anthrax spore may be one micron wide and two or three microns long, just the right size to reach deep into the respiratory pathway.

A spore is so tiny that a cluster of thousands, which would be enough to kill someone, is scarcely visible to the naked eye. A thousand spores side-by-side would barely reach across the thin edge of a dime. Once inhaled, the spores are drawn into the bronchial tree where they travel through numerous branches deep in the lung. Near the tips of the branches are microscopic sacs called alveoli. It is in these sacs that inhaled oxygen is exchanged with carbon dioxide.

Stationed among the alveoli are armies of defender cells called macrophages. These cells sense foreign micro-invaders and engulf them. A pulmonary macrophage normally destroys its inhaled captive and taxis it to the lymph nodes in the mediastinum, the area between the lungs. But in the case of anthrax, spores may transform into active, germinating organisms before the macrophage can affect them. The bacteria then can reproduce and release toxin that destroys the macrophage. Thus, in a perverse turnabout, the anthrax bacteria, like soldiers in the Trojan Horse, can burst out of their encirclement, into the lymph and blood systems.

An infected person at first is unaware that a gruesome cascade is underway. Although the onslaught is relentless, symptoms do not appear immediately. Fluids that have begun to accumulate in the mediastinum gradually pry the lungs apart. Breathing becomes increasingly difficult, and after a few days, a person feels as if his head is being held underwater, permitted to bob up for a quick gulp of air, and then pushed under again.

The agony works its way throughout the body. Nausea gives way to violent, bloody vomiting. Joints are so inflamed that flexing an arm or leg becomes an act of torment. Bloody fluids squeeze between the brain and skull, and the victim’s face may balloon out beyond recognition. The tightening vice around the brain causes excruciating pain and delirium.

Survival depends on being provided appropriate antibiotics before the bacteria have released so much toxin that the body cannot recover. If inhalation anthrax is not treated in time, almost all victims suffer a tortured death. One organ after another is decimated--the lungs, the kidneys, the heart--until life is sucked away.

It is because of such ghastly effects that anthrax and other biological agents have been prohibited as weapons by international agreement. The treaty that bans their development or possession by nations, the 1972 Biological Weapons Convention, uniquely describes their use as “repugnant to the conscience of mankind.” Yet, despite this widely accepted moral precept, a germ weapon is seen by some, not as a shameful blight, but as a preferred instrument of terror.

Dr. Larry Bush Recalls the First Anthrax Diagnosis, on Robert Stevens, in 2001:

"The patient came to the emergency room [at JFK Medical Center in Atlantis, Florida] around 2:15 in the morning on Oct. 2, 2001. He lived real close to the hospital and he and his wife had just come back from a trip to North Carolina. . . .

"When he was up there and not feeling well, he didn’t want to go see a doctor. She said they had driven by Duke University at one point and she had urged him to go in the ER but he didn’t want to go. In fact he drove the car back home back to south Florida from North Carolina that Monday. I’d say that’s around a 12-hour ride. . . .

"They went to sleep, about 8 o’clock. Then she found him awake at around 2 in the morning and he was sort of putting his clothes on in the bathroom. He had vomited and he was confused and febrile. He had a thermometer out but he was confused. He had gotten dressed. So she put him in the car and she drove him over to the emergency room here at JFK, which is about 5 minutes from where they live. So he got to the ER 2:15 a.m. and the initial feeling here was quote 'sepsis,' whatever that means, and they ordered blood work and a chest X ray. Shortly thereafter he became less responsive and had a seizure. He was then intubated more to protect his airway than for any respiratory problem. . . .

"So after the seizure and after he was intubated and had been sedated for the intubation, they did the spinal tap under fluoroscopy in the radiology department. I’d say this was done about 6:30 or 7 in the morning—about 4 hours after he was brought here.

"When I got to the hospital I already knew the spinal fluid was in the lab. I went over and looked at it under the microscope. . . . I saw what was obviously a bacillus in the spinal fluid. When you think of all the bacilli that can cause somebody to be that ill, there are probably 3 or 4 of them. Anthrax is one of them. There is one called Bacillus cereus, which you can see with trauma or with immunocompromised patients. There is Bacillus subtilis, which, again, we occasionally see in the blood stream. I’ve never seen it in spinal fluid. And then there’s Bacillus anthracis. When I looked at the Gram stain I knew it was a bacillus. I thought of the handful that can cause serious disease. Remember, I’m an infectious disease doctor and I’m a microbiology person before that—that was my undergraduate training. . . .

"So then I went to see him and after examining him and talking with his wife, I called back to our microlab and talked to our head tech and I told her 'We have this bacillus. My feeling is we need to prove or disprove it’s anthrax.'

"You can do certain tests that you can get information back within the first 6 to 12 hours, that won’t necessarily confirm anthrax but would differentiate anthrax from, let’s say, the other organisms I’m talking about. Some of those are motility tests, to see if the organism is motile versus not. Some of them are hemolysis tests to see whether it’s hemolytic, you know breaks up blood cells on the agar plate. Some of them have to do with penicillin sensitivity, etc. We were able to do some of those tests early on and they all fit what anthrax would fit, whereas if any of those tests gave another answer, you know motility or Beta hemolytic, or whatever, then that would take them away from anthrax. . . .

"By about 3 in the afternoon we had several tests back.—the motility test, the hemolysis—and everything still fit anthrax. So I said 'You know what? This looks like it could well be anthrax.'

"We’re a Level A lab—all micro-laboratories in hospitals are Level A. A Level B lab is more of a research lab or a state lab or a CDC lab and they could do further specific testing. At this point the organism is starting to grow in the patient’s blood culture too. . . .

"So we called our state reference lab which is in Jacksonville and spoke with head micro-tech there. I spoke to him, as well as our lab tech, and I told him that we were overnighting him an organism that I believe to be anthrax, that our preliminary tests look like it could be anthrax, and what could he do in his Level B lab that was rapid.