By GINA KOLATA
Published: October 5, 2001

A 63-year-old Florida man has contracted pulmonary anthrax and has been hospitalized with the infection, health officials said yesterday.

But, the officials said, there is no evidence that the man's disease was caused by a terrorist attack and there is no public health risk.

''It is an isolated case, and it is not contagious,'' Tommy G. Thompson, the secretary of health and human services, said at a White House briefing yesterday afternoon. ''There is no terrorism.''

Anthrax, a bacterial infection, is rare in people but common in farm animals like sheep, cattle and goats. The infectious bacterial spores can persist in soil for years.

The Florida man was described as an outdoorsman who lives in Lantana. He was hospitalized on Tuesday, the Palm Beach Health Department reported. He had returned from a visit to North Carolina, but the only place he was known to have visited was Duke University, about a week ago, said Debbie Crane, a spokeswoman for the North Carolina Department of Health and Human Services, which is helping investigate the infection.

Ms. Crane added that it could take about a week for symptoms of pulmonary, or inhalation, anthrax to appear. But, she said, health officials are still tracing the man's route and he could have become infected in North Carolina or Florida.

Hospitals and health departments from North Carolina to Florida were asked whether any patients had similar symptoms, and none were reported, the Centers for Disease Control and Prevention said.

''Anthrax happens,'' Ms. Crane said. ''It's happened forever, and it's happened before Sept. 11.''

The pulmonary form is unusual in humans, and although it is the form that would be used by terrorists, this case, health officials said, in no way implies terrorism.

According to an article published in August by the centers, only 18 human cases of pulmonary anthrax were reported in the United States in the 20th century, the latest in 1976.

Last year an epidemic of anthrax occurred in animals in North Dakota, where 32 farms were quarantined, the centers said. One hundred-fifty-seven animals died, and a man who handled cows that died of anthrax became infected but recovered after he was treated with antibiotics.

The man had cutaneous anthrax, meaning that the infection began in his skin, the most common way the bacteria infect humans. Before his case, the disease centers said, the last human case in the United States was in 1992. Two suspected cases were reported in Texas this year.

Even less common is intestinal anthrax, contracted by eating the meat of an infected animal.

Without treatment, 90 percent of pulmonary anthrax cases are fatal, and even with treatment, the disease is very hard to control after symptoms develop.

In Russia in 1979, anthrax spores were released accidentally from a military germ research laboratory. Seventy-nine cases of pulmonary anthrax were reported, and 68 of the victims died.

Anthrax, however, does not spread from person to person, and there is no reason to attribute a single case to terrorism, health officials said.

Dr. Jeffrey P. Koplan, the director of the disease centers, told The Associated Press, ''We will develop a very intense investigation of this case,'' but he emphasized, ''There's no need for people to fear they are at risk.''

Correction: November 1, 2001, Thursday An article on Oct. 5 about a news briefing on the first of the series of pulmonary anthrax cases quoted incompletely from two comments by Tommy G. Thompson, the secretary of health and human services. Parts of the incomplete quotations were repeated in an article on Sunday about the nation's minimal experience with anthrax.

According to a transcript from his office, Mr. Thompson said, ''Based on what we know at this point, it appears it is an isolated case,'' and later said, ''But I want to point out once again that this is an isolated case, and it's not contagious'' (not ''It is an isolated case, and it is not contagious''). Before being interrupted by a question, he also said, ''There's no evidence of terrorism -- at this ---- '' (not ''There is no terrorism'').

By NICHOLAS WADE
Published: October 9, 2001

With the discovery that a second person in Florida has breathed anthrax spores, experts on the disease are finding it hard to come up with a plausible natural explanation. Though they think such an explanation may still emerge, they are leaning toward the possibility that the spores were deliberately spread.

Anthrax occurs from time to time in animals but is rare in humans, at least in the United States. People who handle hides or carcasses of infected animals occasionally catch the disease through the skin, in a form known as cutaneous anthrax.

Inhalation anthrax, contracted by breathing spores of the bacterium, is even rarer. Only 18 cases have been reported in the United States in the last century, and all are believed to have originated from special environments where airborne anthrax spores are common -- bone meal plants or wool sorting factories, for instance, or laboratories studying the organism.

Neither Robert Stevens, who died of inhalation anthrax last week, nor Ernesto Blanco, a co-worker who has now been found to have anthrax spores in his nasal passage, is yet known to have visited any such place. Nor is the American Media building in Boca Raton, Fla., where both of them worked, known to have ever been home to such activities.

Spores of the anthrax bacterium can last for years in the soil and are often breathed in by grazing animals, which can then contract the disease. But another odd feature of the Florida cases is that anthrax is not at present endemic in the United States east of the Mississippi.

One case of inhalation anthrax in a Florida office building would be surprising enough; two are even harder to explain. ''It's a mind-stretching coincidence that doesn't fit the pattern of any known natural outbreak,'' said Dr. Matthew S. Meselson, an expert on biological warfare at Harvard University.

Dr. David Walker, an anthrax expert at the University of Texas Medical Branch at Galveston, said he had ''a hard time making this into a natural exposure,'' though he added that ''no one should jump to any conclusions'' until a lot more evidence was gathered.

Dr. Martin Hugh-Jones, an anthrax expert at Louisiana State University, said that in those cases where inhalation anthrax existed, it occurred in places like wool and hair mills and among renderers or people handling hides. ''That's why this is so odd,'' he said. ''It's a Joe Blow working in an office.''

Several experts have speculated about possible natural routes of transmission in the Florida cases: perhaps a dead infected animal was trapped in the American Media building's air ducts, or Mr. Stevens might have brought an infected leather item into the building and then sniffed and shaken it.

But inhalation anthrax is not known to have spread in those ways in the past.

Nor do experts believe that inhalation anthrax might have occurred sporadically in Florida but gone undetected by being dismissed as pneumonia. ''Somebody might not figure out right away that it was anthrax, but I doubt they would call it pneumonia,'' said Dr. Glenn Songer, a veterinary anthrax expert at the University of Arizona. ''When you take into account the pathology and other signs, there is just nothing else like it.''

Florida health officials said one sample from the American Media building, taken from Mr. Stevens's keyboard, had tested positive for anthrax. Dr. Walker said the keyboard sample could not have come from Mr. Stevens, because infected people do not breathe out spores. They carry the bacterium in their blood, but the bacterium does not form spores, its infectious form, until after the patient's death.

Because spores are not exhaled, anthrax is not spread from person to person. So experts believe that Mr. Stevens and Mr. Blanco must have been infected independently from the same source.

Several experts on anthrax who have considered the possibility of deliberate spread believe that it would be difficult though not impossible for an amateur to concoct a lethal preparation of anthrax, and that spreading it efficiently would be more difficult still. 

Provided a source of anthrax can be found, the bacillus can be brewed up in kitchen conditions and made to form spores. The spores are highly dangerous if breathed in, but simple precautions will protect the brewer.

On the other hand, the Aum Shinrikyo sect in Japan, with many resources available to it, tried hard to make an infectious anthrax preparation and failed.

William C. Patrick 3rd, a maker of germ weapons for the United States before President Richard M. Nixon renounced them in 1969, said the Florida incident appeared to be crude bioterrorism. ''It looks like a poor grade of product.'' he said, ''and poor disseminating efficiency.''

Agreement came from Richard Spertzel, former chief of United Nations biological inspection teams in Iraq.

''The one thing that's reasonably certain,'' Dr. Spertzel said, ''is that the Florida case is intentional.''

THIS ARTICLE WAS REPORTED AND WRITTEN BY GINA KOLATA, WILLIAM J. BROAD AND LAWRENCE K. ALTMAN.
Published: October 12, 2001

Inhalation anthrax, the form of the disease that killed Robert Stevens, a photography editor in South Florida is so rare that very few doctors have ever seen it. But anthrax is a common disease of livestock and other animals in much of the world and the bacterial spores that produce it are commonplace in the soil of many countries.

In this country, anthrax is rare even among animals, said Dr. Martin E. Hugh-Jones, an anthrax expert at Louisiana State University. He said fewer than 100 farm animals contract the disease in the United States in a typical year.

Cases among people are even rarer, and the inhalation form is rarer still.

Anthrax is caused by a bacterium, Bacillus anthracis, and is transmitted by spores that can enter the body in three ways: it can be inhaled, ingested or can enter the skin through a scratch or cut.

Worldwide, most people who contract anthrax get the cutaneous form, in which spores enter the skin, usually through a cut or a scratch. Most of the time, these cases occur in people who handle animal hides or wool that contained anthrax spores. In the United States, 224 human cases of cutaneous anthrax were reported from 1944 to 1994.

In southwest Texas this summer, a ranch worker became infected after he cut himself skinning a buffalo that had died of the disease. The man recovered after taking antibiotics.

When anthrax spores infect the skin, the infection starts out like a small itchy insect bite. The lesion develops into a pus-filled blister, which crusts into a black scab. Symptoms include fever, malaise and headache. Untreated, about a quarter of those affected die because the anthrax bacteria enter the bloodstream, causing an overwhelming infection and releasing toxins. Treatment with antibiotics reduces the death rate to about 1 percent.

People who eat undercooked meat from animals that were infected with anthrax can contract gastrointestinal anthrax, in which spores germinate into bacteria in the intestines, causing nausea, vomiting, fever and abdominal pain. Untreated, about 25 to 60 percent of people with ingestional anthrax die. Worldwide, relatively few anthrax cases have been gastrointestinal.

Inhalation anthrax, the form that affected the man who died in Florida, is extremely rare and by far the most deadly form of the disease. Only 18 cases were reported in the United States in the 20th century.

How Anthrax Works

Much of what is known about how the disease progresses was learned from a single outbreak, in the Soviet Union in 1979, in which 79 people are known to have been infected at once from an accidental release of anthrax spores being grown in a germ warfare laboratory on a military base in Sverdlovsk. Sixty-eight of them died and 42 had autopsies.

The disease starts when a person inhales spores into the lung. Once there, the spores travel to lymph nodes in the mediastinum, in the middle of the chest, a journey that can take just a few hours. There, in the lymph nodes, in a process the Sverdlovsk outbreak shows can take anywhere from days to weeks, the spores in the lymph nodes turn into anthrax bacteria, which begin producing deadly toxins that attack body tissues. Because the timing of this germination process can vary, it is hard to know until about 60 days have passed if a person who inhales the spores has the disease.

But once the spores germinate, it does not take long for symptoms to appear, said Dr. Jerome Hazen Smith, a retired pathologist at the University of Texas Medical Branch at Galveston who examined autopsy tissues from the Russian anthrax victims. They are caused by the toxins, which kill cells and cause fluids to accumulate in tissues.

The first symptoms are nonspecific -- like fever, cough, headache, vomiting and chills. But within hours to a few days, the disease enters a second phase. Patients have trouble breathing because their lungs are compressed by fluid in the mediastinum. They sweat profusely and go into shock because their blood vessels leak and their blood pressure drops. About half the patients have blood-filled fluid in the tissue covering their brains, which compresses the brain, causing coma and delirium. Once the second phase begins, death can occur within hours.

The disease is so distinctive, said Dr. David Walker, a pathologist at the University of Texas at Galveston who helped examine autopsy material from the Russian victims, that a Russian pathologist, Dr. Faina A. Abromova, recognized immediately what had killed them. Beneath a victim's skull, she saw a hallmark of inhalation anthrax: the lining of the brain, filled with blood.

'She said: 'Oh. It's the cardinal's cap. I remember that from when I was a student. That's anthrax,' '' Dr. Walker recalled.

Dr. Walker said that, for him, the blood-filled fluid in the mediastinum, the tissue in the middle of the chest, was what tipped him off.

Treating Exposed People

Because there are so few cases of human anthrax, and because it would be unethical to deliberately expose people to the bacteria in tests, little is known about treating people exposed to it. But experiments with animals have provided some clues.

A wide variety of antibiotics, like penicillin and doxycycline as well as ciprofloxacin and other antibiotics in its class -- the fluoroquinolones -- can kill anthrax bacteria, but only if they are given before symptoms appear. By the time a person is ill, the bacteria have already released large quantities of their deadly toxins into the body. Experts have recommended treating asymptomatic people who may have been exposed to anthrax for 60 days.

Ciprofloxacin is the only drug identified by the Food and Drug Administration as a treatment.

Federal officials say they can fly supplies of antibiotics and other drugs within 12 hours anywhere in the county for an outbreak of anthrax or other bioterrorism emergency. The government has arrangements with drug makers to have fresh supplies available on an emergency basis.

The government's emergency program includes the National Pharmaceutical Stockpile, which was mobilized for the first time in response to the terror attacks on Sept. 11.

The nation's current supply of anthrax vaccine was licensed in 1970 by the Food and Drug Administration to prevent the form of anthrax that afflicts the skin. It had proven effective in clinical trials on factory workers who handled large amounts of goat hair. In 1985, the Army solicited proposals for pharmaceutical manufacturers for an improved vaccine. None of the major drug makers bid on the contract. No war threatened, the disease was rare, and there was little profit in making vaccines that were not used widely.

This vaccine is now given to military personnel, but its effectiveness against inhaled anthrax has been questioned. Its manufacturer, Bioport, of Lansing, Mich., is not now making the vaccine because its factory does not meet Food and Drug Administration requirements.

Avant Immunotherapeutics, a biotechnology company in Needham, Mass., announced on Wednesday that it had licensed some of its vaccine technology to a government contractor that is working on vaccines against biowarfare agents.

But the company said it could not comment on what technology was licensed or what pathogens the vaccines would be directed against. On its Web site, Avant says it has done preclinical work on a vaccine for anthrax. But the company would not return calls today seeking comment.

The genome of the anthrax bacterium is being sequenced at The Institute for Genomic Research, a nonprofit organization in Rockville, Md. The job should be done in a few months, said Timothy D. Read, who is in charge of the project there.

Anthrax in History

Anthrax has been known since biblical times. The fifth plague described in the Book of Genesis as killing the Egyptians' cattle resembles anthrax and the disease is described in the early writings of Hindus, Greeks and Romans. An epidemic hit Europe in the 17th century.

Anthrax bacteria are named for the Greek word for coal, anthrakis, because they cause coal-black lesions when they infect the skin. The bacteria's life history -- and the etiology of the disease they cause -- were discovered in the mid-19th century by Robert Koch, a German bacteriologist who was a developer of the germ theory of disease. He was intrigued by the infection, which was occurring among farm animals in the Wollstein district, where he lived, and set out to prove that the anthrax bacteria were causing the disease.

Koch discovered that he could inject mice with anthrax bacteria taken from the spleens of infected animals and the bacteria would grow in the blood of the mice, giving them anthrax. But, he asked, could he produce the disease if he used bacteria that had not been growing in another animal?

So Koch grew anthrax bacteria in the aqueous humor -- the transparent fluid -- from an ox's eye. That led him to discover that the bacteria, which are relatively fragile, transform themselves into tough and resilient spores when they run out of food, or experience heat or chemical shock. The spores can survive for years in the soil and it is through spores that the disease is spread. 

That is why anthrax does not spread from person to person -- the bacteria do not produce spores while they are actively growing in an infected person.

For much of the 20th century, the world's top militaries investigated anthrax as a weapon, and some even used it. Germany, for instance, engaged in anthrax warfare in World War I against Allied horses, which were crucial to the war effort.

In 1998, scientists in Norway and Britain announced that a lump of sugar from that era contained living anthrax spores, apparently placed there 80 years earlier by a German spy intent on disrupting the Allied horse- and reindeer-drawn supply lines across northern Norway.

Washington first made anthrax munitions in World War II, fearful that Tokyo and Berlin were making germ weapons. After the war, the Army built a windowless prototype factory at Camp Detrick, Md., for making anthrax.

In time, workers there learned how to increase the potency of anthrax so that a single gallon held up to eight billion lethal doses -- enough, in theory, to kill everyone on earth. Two Detrick workers exposed accidentally to the spores died.

During the cold war, Moscow built a secret anthrax enterprise whose annual production capability of 4,500 metric tons of anthrax dwarfed Washington's one-ton annual effort. The United States gave up its germ arsenal in 1969. But the Soviet Union, after signing a global treaty in 1972 that banned biological weapons, worked even harder to develop them.

Terrorists have tried and failed to make anthrax weapons. Aum Shinrikyo, a Japanese cult that in 1995 attacked Tokyo subways with nerve gas, had earlier launched unsuccessful germ attacks meant to kill millions of people. Its chosen banes included anthrax.

Dr. Richard Spertzel, a former head of biological inspections in Iraq for the United Nations, said Baghdad tested crop-dusting gear to spread anthrax before the Persian Gulf war but had trouble getting it to work.

The hurdles to making anthrax weapons include getting the right strain of the bacteria. Experts say there are scores of strains of Bacillus anthracis, only some known to be exceptionally deadly.

Then a would-be biowarrior would have to brew swarms of the microbes and then change the growing conditions so that the fragile rod-shaped bacteria form spores.

Then clumps of spores must be refined to precise specifications if they are to find their way into the human lung. Weapons experts say the particles must be one to five microns wide; 20 of them would line up across the stalk of a human hair.

Dr. Hugh-Jones, the anthrax expert at Louisiana State University, said terrorists could not simply open a jar of anthrax spores on a subway or sprinkle some spores around and infect thousands of people. A person must inhale 8,000 to 10,000 spores to be infected, Dr. Hugh-Jones said. And, he added, ''getting an efficient aerosol is a lot of work -- you can't just pump it up in an aerosol can.''

Anthrax spores, Dr. Hugh-Jones explained, tend to clump together in pieces so big that they would be taken up by the body's defenses in the bronchi. To make the spores into a deadly power, ''you've got to have a very, very fine particle size,'' Dr. Hugh-Jones said. To make that powder, he said, ''you have to use detergents,'' to break up the clumps. ''It's a professional weapon -- it's not for the amateur,'' he said.

For instance, commercial crop-dusters usually dispense liquids, and their nozzles produce droplets far too large for sailing deep into human lungs. A terrorist would have to do major modifications to adapt the sprayer's nozzles to produce a finer mist of particles.

Nozzle design problems were among the factors that hurt Iraq's anthrax efforts, Dr. Spertzel said.

Experts say dry anthrax is even more difficult to make than wet anthrax, but more effective because it can sail farther on the wind.

Because all anthrax spores are vulnerable to bright sunlight, they would ideally be dispersed at night, when the logistics of nighttime aerial strikes can be complex, experts say. Even then, an attack can fail if the weather is bad or if the spores are caught up in the rising air currents often produced by the relative warmth of urban areas. 

''People don't understand how difficult it is to pull off a biological attack,'' said David R. Franz, a former official in the Army's germ-defense program and now an officer at the Southern Research Institute, at the University of Alabama.

The Florida Case

Is the Florida case a military-type anthrax weapon? Scientists familiar with the federal investigation said no exact match had been made between samples of the Florida bacteria and other known strains, or subspecies, of anthrax. But they added that preliminary tests pointed away from its being one of the well-known stains used over the decades to make anthrax weapons, and away from prevalent strains found in germ banks, which distribute microbes to hospitals, businesses and universities for diagnostic purposes as well as research on new medical treatments.

So far, weapons experts say, the Florida case appears to be crude bioterrorism. Dr. Spertzel, the former head of biological inspections in Iraq for the United Nations, and William C. Patrick III, a maker of germ weapons for the United States before President Richard M. Nixon renounced them in 1969, say the Florida anthrax particles apparently came in three sizes, which they said would suggest that if a terrorist planted them he was a beginner.

Very small particles, the experts hold, would have gone deeply into the first victim's lungs. Larger particles would have lodged in the second victim's nose. And still larger particles would have fallen on the keyboard.

''The one thing that's reasonably certain,'' Dr. Spertzel said, ''is that the Florida case is intentional.''

By LAWRENCE K. ALTMAN
Published: October 19, 2001

The response to the new anthrax case at CBS News was decidedly lower-key than the response to the very similar case at NBC last week, health officials said yesterday, because epidemiologists are applying the lessons they have learned since they began their investigation.

The CBS News building, on West 57th Street in Manhattan, was not evacuated. Workers -- including the woman who tested positive for anthrax spores -- remained at their jobs. And health officials did not recommend antibiotic treatment for large numbers of workers. All this was in sharp contrast to the response at NBC when a case of cutaneous anthrax was diagnosed in an assistant to Tom Brokaw on Oct. 9, said Dr. Stephen M. Ostroff, an epidemiologist from the Centers for Disease Control and Prevention.

''We have so much more information based on our experience and what the epidemiologic patterns tell us,'' Dr. Ostroff said in an interview.

The woman at CBS developed cutaneous anthrax, the most treatable form of the disease, on her cheek on Oct. 1. The source of the infection is not known; although she handled mail, she did not recall having opened a letter and being exposed to powder.

It is not clear when she was exposed to anthrax spores, but the normal incubation period for cutaneous anthrax is one to seven days. Anthrax is not contagious, so the risk of her co-workers' developing it is almost negligible, said Dr. Ostroff, who is in New York City supervising the agency's investigation of cases associated with NBC, ABC and CBS.

Epidemiologists have found that the circumstances at all three networks appear similar.

Only one person has developed cutaneous anthrax at each network, Dr. Ostroff said. Also, anthrax spores have not been identified in any of the nasal swabs taken among more than 300 co-workers of Erin O'Connor, the NBC employee who developed cutaneous anthrax, Dr. Ostroff said.

Health officials now say that when a significant period of time has elapsed between exposure and detection of illness, most co-workers do not require antibiotic therapy for prevention of infection. Avoiding unnecessary treatment eliminates the risk of adverse side effects and development of resistant microbes.

Although the CBS epidemiologic investigation is in a very early stage, Dr. Ostroff said, ''certainly the circumstances that we are aware of to date suggest that things are not particularly different there than they are at the other two networks.''

''You would have to assume that what was dispersed into the environment was not dispersed at levels that were sufficient to produce human illness unless you were in the very proximate area where this letter was opened,'' he continued. ''If the vast majority of employees at NBC probably were not exposed at levels that could be associated with a risk for illness, then it is better that these individuals not take chemoprophylaxis if they do not need it.''

The situation at the networks in Manhattan differs from that in Washington, where all six House and Senate office buildings were closed yesterday for screening tests because 31 workers on Capitol Hill were exposed to anthrax spores from a contaminated letter sent to the office of Tom Daschle, the Senate majority leader. Dr. Ostroff said the response in Washington was so vigorous because the letter was opened so recently, on Monday; New York City health officials would probably respond the same way if the epidemiologic investigation were to begin about the same time as the workers were exposed at the networks.

A few spores have been found at NBC. The network is conducting an extensive cleanup to remove them even though they do not pose a significant risk to workers. ''It's just better not to have them there,'' Dr. Ostroff said.

Dr. Ostroff said health workers had found nothing to suggest a continuing health risk at ABC.

At least three investigations are going on simultaneously in the anthrax cases: clinical, epidemiologic and criminal. The extent of the testing that epidemiologists will do among workers and the environment will vary with the site and the needs for such information in each investigation, Dr. Ostroff said.

By ABIGAIL ZUGER, M.D.
Published: October 23, 2001

Even as New Yorkers flinched at every new mention of anthrax last week and fought rising panic, the regular Monday meeting of the city's infectious disease specialists unfolded more or less as usual.

True, there were two cases of anthrax in the city, possibly more. But there was also a case of cholera here last spring. An unusual, near-fatal case of the dire food poisoning known as listeriosis surfaced over the summer. A young German man picked up a peculiar, disfiguring case of H.I.V. A businessman came down with a bizarre fungal infection on the golf course. A Mexican deliveryman almost died from inhaling a rare soil organism common in Central America.

Against the panorama of microbes that routinely wander through this city and threaten its residents, the hypothetical threat of anthrax seemed to fade a little.

For 30 years, the Monday afternoon infectious disease meeting has drawn specialists from around the metropolitan area. Every week, doctors take turns describing the most interesting, perplexing or alarming infections they have seen.

Back in 1979 and 1980, when AIDS, still unnamed, was sending a trickle of sick patients into New York hospitals with puzzling symptoms, it was the overview at this weekly meeting that gave city doctors a vision of a new and frightening pattern of illness well before the rest of the country caught on.

Last Monday, the anthrax scare created exactly the opposite situation: the name of a disease was resonating through the city, but the regulars at the meeting had no actual cases to discuss. The single case of cutaneous anthrax to have been identified here at that point had been treated for two weeks and the patient was doing well. Any other cases were still hypothetical.

''We thought the collective wisdom of this group could be extremely useful to the city at this point,'' said Dr. Stephen Baum, head of medicine at Beth Israel Medical Center, president of the Infectious Disease Society of New York and a member of the mayor's task force on bioterrorism. Dr. Baum took the podium at the start of the meeting for a brief brainstorming session about anthrax.

Not one of the 150 doctors in the auditorium was seriously worried that a tide of infection was about to drown the city. Anthrax, which is not transmitted from person to person and is treatable with antibiotics, is not a scary organism in these particular circles. It is not nearly as frightening and potentially dangerous as, for instance, the drug-resistant tuberculosis germ that swept through the city in the early 1990's, killing hundreds.

It was the rising tide of unnecessary anthrax panic that bothered the doctors, and also the obsession with the antibiotic Cipro, when drugs related to Cipro should also treat and prevent anthrax, and penicillin and tetracycline should be safer and cheaper alternatives for most patients.

The anthrax discussion took half an hour. Then Dr. Baum steered the meeting back to the usual weekly routine of hearing about other infections that somehow never made it onto the front page:

After a 61-year-old man ate raw oysters at a city restaurant last spring, he developed severe abdominal cramps and diarrhea. He had cholera. Sewage from foreign tankers can easily contaminate shellfish beds with alien organisms. The man was treated and recovered.

A 26-year-old Mexican had a cough for two years as he delivered packages. He grew steadily weaker and sicker. When he came to Bellevue gasping for air, doctors found his windpipe almost blocked by small growths caused by Klebsiella rhinoscleromatis, a rare germ living in the soil of Central America. He was treated and is recovering.

A 53-year-old woman with advanced ovarian cancer had one intestinal blockage after another. She proved to have an infection with Listeria, the bacteria that often contaminate cheese and processed meats. She was treated and felt better.

A 65-year-old New Jersey man developed a large sore in his genital area that refused to heal despite dozens of tests and seven medications. It turned out that he had sporotrichosis, a fungal infection from plants; he probably picked it up when he urinated against a bush at his favorite golf course. 

A 36-year-old woke up to find his face frozen. He could not raise his eyebrows, smile or eat. Tests showed that he was newly infected with H.I.V., and on treatment, his facial muscles began to work again.

By the end of the afternoon, anthrax had faded into the background, just one more hostile particle to try to outsmart amid hundreds of others.

By LAWRENCE K. ALTMAN
Published: October 23, 2001

People with inhalation anthrax may survive if their cases are diagnosed promptly and they receive aggressive treatment in the early stages of the infection, experts in infectious disease say, basing their opinions partly on the course of the illness in two of the cases diagnosed this month.

Dr. Frank Bia, an infectious-disease specialist and microbiologist at Yale University, said inhalation anthrax might be like other bacterial infections that respond to treatment if antibiotics are started in time.

Although Robert Stevens, 63, died of inhalation anthrax, a co-worker in Florida, Ernesto Blanco, 73, is gradually recovering.

Two postal workers in Washington also have inhalation anthrax.

One, Leroy Richmond, is in serious but stable condition at a hospital in Falls Church, Va. Doctors are cautiously optimistic that Mr. Richmond, who developed symptoms at midweek, will recover. He worked at the post office that handles all mail delivered in the capital, but the source of his infection is not known.

The second postal worker, whose identity was not disclosed, is also in a hospital.

Two other postal workers in Washington died yesterday, health officials said, and anthrax was suspected as the cause. The chief medical examiner for the District of Columbia identified one of them last night as Thomas L. Morris Jr. A friend and neighbor identified the other as Joseph Curseen, 47, of Clinton, Md. It is not known how long the workers had been ill before seeking medical help.

Mr. Stevens, who died on Oct. 5, had the first recognized case of inhalation anthrax from the deliberate dispersal of spores. He was a photo editor at American Media Inc. in Boca Raton, Fla.

Mr. Blanco, his co-worker, is recovering at Cedars Medical Center in Miami after leaving an intensive care unit, where his breathing had been assisted by a mechanical respirator. His stepdaughter, Maria Orth, told The Associated Press that he was ''doing great.''

Anthrax was not suspected when Mr. Blanco, who suffered from chronic lung disease, was admitted to Cedars for pneumonia on Oct. 1. The underlying lung disease might have made him more susceptible to inhalation anthrax. Because he worked at American Media, a swab of his nose was taken, and it showed anthrax spores. He did not show classic symptoms of inhalation anthrax, which suggests that doctors may need to modify their description of the condition, and his case was re-classified as ''atypical inhalation anthrax.'' The change was based on laboratory tests that showed evidence of Bacillus anthracis in bloody fluid in the sac covering his lungs.

The Centers for Disease Control and Prevention has omitted some information about Mr. Blanco's case of a type usually included in its weekly reports. Nevertheless, Mr. Blanco's improvement and Mr. Richmond's potential recovery raise intriguing questions about survival from inhalation anthrax, which textbooks and scientific articles describe as nearly always fatal.

Anthrax spores can cause different types of infection, depending on where they enter the body. If they invade via a break in the skin, the result is cutaneous anthrax, which often resolves without treatment and is easily cured by antibiotics. But if the spores are breathed into the lungs, inhalation anthrax can occur. Doctors believe that the inhalation form is often fatal because by the time the symptoms of infection appear, a bacterial toxin is already doing its deadly work, and it may be too late for antibiotics to help.

Survival from inhalation anthrax depends on recent improvements in the support of patients with serious respiratory disease, the development of more antibiotics and other types of drugs; and wider use of intensive care units, mechanical respirators and, when needed, dialysis machines to support failing kidneys.

The earlier estimates of high mortality for inhalation anthrax rely mainly on three limited databases.

First, of the 18 cases of inhalation anthrax that had been reported in the United States since 1900 until this month, 16 were fatal. 

Second, an epidemiologic study in 1957 found that four of five workers died after contracting inhalation anthrax at a goat-hair processing plant in Manchester, N.H., over 10 weeks. The workers were all too familiar with anthrax; in the previous 16 years, 136 had developed cutaneous anthrax, the most curable form. Although air sampling showed that workers often breathed Bacillus anthracis spores at the plant, none developed inhalation anthrax until 1957.

The third database derives from research conducted in 1993 of an outbreak that occurred in Sverdlovsk, Russia, in 1979 when a windblown plume of Bacillus anthracis released from a germ warfare facility led to at least 96 cases of skin and inhalation anthrax.

Much of the Sverdlovsk evidence comes from an investigation conducted by American and Russian doctors 14 years after the accidental release of spores there. Dr. Kent A. Sepkowitz, the chief of infectious diseases at Memorial Sloan-Kettering Cancer Center in Manhattan, credited the investigators for their ingenuity in reconstructing the course of the epidemic from what remained of records that Soviet officials had deliberately destroyed.

But when Dr. Sepkowitz recently reviewed the data from that investigation, he said he found what he believed was a methodological flaw that inflated the death rate. Because no one knows precisely how many people in Sverdlovsk developed symptoms, the investigators had to calculate the death rate by including only dead people and those sick enough to be hospitalized. They had no way of knowing how many others might have been infected but recovered without seeking medical help.

''So we may be citing the wrong number and fanning a flame,'' Dr. Sepkowitz said.

He also said that ''unless anthrax operates by a set of rules unique among bacteria, one would expect to encounter a spectrum of disease,'' from the mild to the severe.

Dr. Stephen Baum, chief of medicine at Beth Israel Hospital in Manhattan, speculated that the recovery rates from inhalation anthrax might even be as high as they are for many other types of pneumonia and respiratory ailments. Pneumococcal pneumonia, for example, is curable. But even if treated in time, it is a serious problem; the lowest death rate is about 15 percent.

Dr. Larry M. Bush, who treated Mr. Stevens, the man who died of inhalation anthrax in Florida, said his patient might never have developed inhalation anthrax had he followed his wife's advice to seek medical attention when he first developed symptoms about Sept. 26, instead of waiting until Oct. 2.

If Mr. Stevens had sought help earlier, a doctor would have realized he had a respiratory infection but would probably not have considered anthrax. Nevertheless, an antiobiotic prescribed for a respiratory infection would probably have successfully treated his inhalation anthrax, Dr. Bush said in an interview.

But if his case had gone undetected, Dr. Bush said, it would have taken longer for other cases to come to attention.

By N. R. KLEINFIELD
Published: October 28, 2001

A third postal facility in central New Jersey was closed yesterday after a small amount of anthrax was discovered on a mail bin.

New Jersey health officials said the bin at the Princeton Main Post Office in neighboring West Windsor tested positive for what they said was a tiny, ''single colony'' of anthrax. Some 60 to 70 people work at the center.

It was the first anthrax found in a New Jersey building since anthrax was discovered at the regional facility in Hamilton Township. The center processed the three anthrax-laced letters that were sent to New York and Washington, and the Princeton office forwards and receives mail from Hamilton.

The acting New Jersey health commissioner, George T. DiFerdinando Jr., said it was conceivable that the results of the Princeton anthrax tests could be attributed to a laboratory mistake or that the bin had traveled from Hamilton. Additional testing was begun.

Dr. DiFerdinando said that the Centers for Disease Control and Prevention in Atlanta did not recommend that the Princeton workers be treated with antibiotics, given the slight degree of possible contamination. However, he said that antibiotics will be made available to any employee who wants them.

Still, the latest development prompted U.S. Representative Christopher H. Smith, Republican of New Jersey, to call for anthrax testing at all 46 postal offices in central New Jersey that receive mail from the Hamilton center. A spokesman for the state Department of Health and Senior Services said that officials were in the process of developing a plan to assess the risks at post offices receiving mail from Hamilton.

Besides Princeton and the Hamilton distribution center, the West Trenton Post Office in Ewing Township has also been closed after a carrier assigned to a route in West Trenton came down with cutaneous anthrax, the skin version. On Friday, health officials admitted that they had erred in previously announcing that tests of 20 samples from West Trenton came back negative, suggesting that the facility was free of anthrax. In fact, Dr. DiFerdinando said those 20 negative samples were from the Hamilton facility, which has had other samples test positive for anthrax.

Yesterday, though, the commissioner said that 20 West Trenton samples taken by the F.B.I. and another 22 taken by the health department have been negative in testing to date, though they are being examined further.

The health department also announced that it was opening a clinic to dispense antibiotics to anyone who worked in or visited the non-public areas of the Hamilton mail center since Sept. 18, when the earliest anthrax letter was postmarked. The clinic, at the Crean Hall Auditorium at the School of Nursing at St. Francis Medical Center in Trenton, will open at 8 a.m. today.

Many postal employees from the distribution center have already begun taking antibiotics, but the health department officials said they wanted to facilitate care by opening a central clinic. They said they did not know how many workers might fit the criteria, but estimated that it could be as high as 2,500.

Health officials have identified five postal workers in the state who are suffering from anthrax-like symptoms, four who worked at Hamilton and one in West Trenton. Two have tested positive for the skin version, and a third is suspected of having the ailment. Two other postal workers may have pulmonary anthrax, the far more lethal form.

In New York, Mayor Rudolph W. Giuliani said there were no new developments on the anthrax front. ''Things are pretty much in the same situation they were in,'' he said. ''No new cases that we know of, at least not at this point.''

However, Neal L. Cohen, the city health commissioner, said that the medical examiner was taking a further look at the death of a postal supervisor, Laura Jones, who died on Oct. 10 and who worked at the Morgan Station distribution center, where anthrax was discovered last week. Her death, which was reported in The Daily News yesterday, had been attributed to hypertensive cardiovascular disease. 

Ellen S. Borakove, a spokeswoman for the city medical examiner, said the office decided to reopen the case after they learned on Friday that Ms. Jones was a postal employee at the Morgan center. Ms. Borakove said Ms. Jones was in her mid-50's and had a history of hypertension. She died at her home in Brooklyn. She was buried and no decision has been made about whether her remains will be exhumed.

Laboratory tests last week found anthrax contamination on four high-speed sorting machines at Morgan Station, the largest mail distribution center in New York City. It is believed that letters sent from Trenton were sorted at Morgan before being sent to NBC and The New York Post.

The center has not been closed, despite protests by the postal union, but a section of the center where the machines are has been cordoned off.

''If the health authorities believe there is a risk,'' Mayor Guiliani said, ''then I am sure they'll close it down.'' 

By GINA KOLATA
Published: October 31, 2001

Inhalation anthrax used to be seen as virtually a death sentence. Now, doctors are not so sure. With 10 confirmed cases in recent weeks, the death toll stands at three, with a fourth patient very seriously ill.

Cutaneous anthrax was so rare and unexpected that no doctor would have considered it until a person developed a characteristic black scab in the middle of a pustule on his skin. No more. In some postal workers, the disease was diagnosed and treated so soon that they never developed the characteristic scab.

As the nation has its first, terrifying experience with anthrax and biological terrorism, medical dogma is being rewritten overnight.

Organizations like the federal Centers for Disease Control and Prevention, the New York City Department of Health and the Infectious Disease Society of America send out regular e-mail alerts and notices to doctors with new advice on how to spot anthrax and the latest revisions in recommendations for treating it. Some, like Dr. Martin Blaser, an infectious-disease expert at New York University School of Medicine, get updates virtually every day.

The greatest danger is from inhalation anthrax, a disease so rare that until the recent cases, almost no doctor practicing in the United States had ever seen it.

Before Robert Stevens, a photo editor in South Florida, died of it earlier this month, there had been only 18 cases reported in the United States in the past century. Most of what was known came from a single incident, in 1979, when at least 79 people were infected and 68 died from an accidental release of anthrax spores from a germ warfare site in the Soviet Union.

Mr. Stevens's anthrax was so unexpected that the disease was not identified until he was near death. The next surprise was that postal workers could contract anthrax from spores in mail. The disease was also not diagnosed when two postal workers became ill -- and later died of inhalation anthrax.

''That's true of almost any epidemic in history -- you miss the first couple of cases,'' said Dr. Craig R. Smith, a member of the Infectious Disease Society of America's bioterroism working group and an infectious disease expert at the Phoebe Putney Memorial Hospital in Albany, Ga. ''If you don't think about it, you can't diagnose it.''

The early symptoms of inhalation anthrax are much like those of flu and other respiratory diseases that strike an estimated 30 million to 100 million people each winter, Dr. Blaser said. But these respiratory diseases are caused by viruses and do not respond to antibiotics.

Inhalation anthrax is caused when spores of the anthrax bacteria, Bacillus anthracis, are breathed into the lungs and swept into lymph nodes in the middle of the chest, the mediastinum.

Once there, they germinate into bacteria that release toxins that attack tissue, causing the symptoms of the disease. Fluid accumulates in the chest, compressing the lungs and making breathing difficult. Blood vessels break down. And about half the patients accumulate bloody fluid in the tissue lining the brain, the meninges.

Anthrax bacteria are killed by antibiotics, but until now most doctors believed that once symptoms appeared, it was too late to begin treatment. Cases in the current outbreaks have changed this view. People whose symptoms were recognized quickly are recovering.

Treatment recommendations are changing too. At first, people exposed to anthrax were treated with the antibiotic Cipro. Later, public health authorities emphasized that other antibiotics, like doxycyclin, were also effective against anthrax, even against the strains involved in the current outbreaks. Last week, the disease control centers gave doctors a list of antibiotics including drugs like clindamycin and rifampin that, unlike Cipro and doxycyclin, can cross into the brain from the blood -- possibly helping to prevent anthrax from causing meningitis -- and recommended using them, too.

Clindamycin and rifampin also impede protein synthesis. Since the anthrax toxins are proteins, these antibiotics might diminish toxin production. 

Doctors are also suggesting other treatment ideas. One is to give patients the blood-pressure drug captopril, which in laboratory studies seems to block toxin synthesis, Dr. Blaser said. He and others are thinking of testing this idea in the event of a large outbreak.

Cutaneous anthrax is usually a much milder disease, easily treated, that occurs when anthrax spores get into the skin, germinate, and produce toxins that affect the immediate area where the bacteria are growing. Doctors would once have dismissed the first signs of cutaneous anthrax -- a small pimple that looks like an insect bite -- and not thought of anthrax until they saw the characteristic black scab, Dr. Smith said. (Indeed, at least one of the first cases in the current outbreak was suspected to be a spider bite.) No more.

On Tuesday, Dr. Smith got a call seeking advice from a doctor who works at a large plant nearby owned by Merck & Company. A person came in with a rash on the forearm, and the doctor immediately thought, Could this be anthrax?

Merck, a large drug company, might be a target of terrorists. It turned out to be just contact dermatitis, a garden-variety rash, Dr. Smith said. But he was struck by the doctor's reaction.

''That change in thinking is all that it takes for doctors,'' Dr. Smith said. 

Health officials investigating the death of a hospital worker in Manhattan said yesterday that the strain of anthrax bacteria that killed her was indistinguishable from that mailed to Tom Daschle, the Senate majority leader, and media companies in Florida and New York.

''As far as the organism itself, we did have a number of cultures from the patient and it is what we call indistinguishable from all of the others,'' said Stephen Ostroff, an epidemiologist from the Centers for Disease Control and Prevention who is helping oversee the New York investigation.

But while federal officials in the past have said that the indistinguishable quality of the bacteria might indicate that it comes from the same source, they have also conceded that this bit of scientific knowledge neither illuminates much about who has been spreading the anthrax nor discounts the possibility that there may be more than one person or groups involved.

In making the announcement at a news conference at City Hall, officials also said that they had uncovered little helpful evidence for solving the question of how the hospital employee, Kathy T. Nguyen of the Bronx, had become infected. Ms. Nguyen, 61, who worked in a stockroom, died early Wednesday at Lenox Hill Hospital in Manhattan.

Tests of Ms. Nguyen's clothes, which health officials said on Wednesday appeared to be contaminated with anthrax, now appear to show that her jeans and sneakers did not contain any of the bacteria. Environmental swabs of the hospital where she worked, Manhattan Eye, Ear and Throat Hospital on the Upper East Side, have also yielded nothing, and the same was true of similar swabs taken in her Bronx apartment building. Of 28 nasal swabs taken from people who worked in close proximity to Ms. Nguyen at the hospital, none have come back positive for anthrax. And another hospital employee who had a suspicious lesion was not infected, tests indicated.

''To this moment, we do not have any evidence of anthrax,'' said Dr. Neal L. Cohen, the city's health commissioner, who said results of additional, more wide-ranging tests of the hospital and home were pending.

Across the country yesterday there was an array of anthrax findings and scares.

In Florida, law enforcement officials said they had intercepted a suspicious letter containing white powder addressed to Gov. Jeb Bush, although initial tests indicated it contained no biological agents. And a New York Post employee who works in the paper's accounting department opened an envelope that appeared to contain a white powdery substance. Law enforcement authorities and C.D.C. officials went to The Post's building, and the contents of the envelope were being tested and the employee who opened the envelope was taking antibiotics. One Post employee recently tested positive for cutaneous anthrax, and two other workers are suspected to have the illness.

But anthrax spores were, in fact, found in four of the five mailrooms of the Food and Drug Administration's headquarters in Rockville, Md. And a day after evidence of anthrax was found in a postal building in Indianapolis, anthrax spores were found at a stamp distribution center in Kansas City, Mo. Some 120 workers at the stamp office were offered antibiotics. However, in both Indianapolis and Kansas City, officials said they believed that the minor contaminations could be linked to anthrax-exposed mail centers in New Jersey and Washington.

In New Jersey, officials have requested immediate federal help to test every post office for anthrax after six people have been infected, all but one postal workers. Acting Gov. Donald T. DiFrancesco asked the new federal Office of Homeland Security yesterday to send to the state forensic experts, lab personnel, medical investigators and other staff.

And in New York, the Postal Service announced that tests showed anthrax on two more mail-sorting machines at the Morgan Station center, at 29th Street and Ninth Avenue in Manhattan, raising the total to six contaminated machines. Postal authorities also said those tests identified spores on a dust-extracting machine not connected to the heating or ventilation system, and that they had been shut down and would be cleaned.

On Monday, the New York Metro Area Postal Union filed a federal lawsuit seeking to close the Morgan facility until a more complete cleanup was done. Judge John Keenan of Federal District Court in Manhattan has scheduled a hearing for next Tuesday. To date, though, no postal worker in Manhattan has contracted the disease, and postal officials said that samples taken at a number of locations in four other Manhattan postal stations had all come back negative.

Investigators working to unravel the mystery of the Bronx woman's infection and death have interviewed what Mayor Rudolph W. Giuliani called ''an enormous number'' of co-workers, friends and neighbors of the woman, a Vietnamese immigrant.

But progress appeared hard to come by. One C.D.C. official said yesterday that a review of the postal routes that could have led to Ms. Nguyen's employer or home has yielded no evidence that mail was the source of the bacteria.

''We are reviewing the routes that mail might have traveled to reach her,'' said Dr. Julie Gerberding of the federal agency, speaking in Washington. ''So far we have found no clues to suggest that the mail or the mail handling was the cause of her exposure.''

As it stands, 1,500 hospital workers, patients and visitors to the small, outpatient hospital where Ms. Nguyen worked are now on antibiotics. In the Bronx, some of Ms. Nguyen's neighbors expressed anger and bewilderment about health officials not taking the same steps in her 29-unit apartment building as they did at the hospital, where employees and many patients and visitors were given antibiotics and, as a precaution, the center was shuttered.

''We need that test,'' said Ed Rivera, one of Ms. Nguyen's neighbors, who filled out a Medicaid application on Wednesday so he could get immediate medical coverage. ''Nobody knows where she got this from. It's only right that we get the same protection as everyone else.''

Dr. Cohen, the city health commissioner, defended the differing approaches. He said that because most anthrax cases in the United States appeared to be related to the mail, and Ms. Nguyen worked in a hospital room that once was close to the building's mailroom, it made sense to take different precautions.

''We did do environmental sampling at the apartment and the mail slot, and at this point we don't see any anthrax or anthrax exposure there,'' Dr. Cohen said.

He added: ''The reality of the way in which anthrax has been delivered in the United States, the relationship to mail delivery, is such that you have to have a greater concern about that mailroom. Until we can rule that out, as a hospital facility where people go in for treatment, surgical procedures, it would be irresponsible to allow people to enter such a facility without absolutely being sure that there is no possible exposure. It is a very different from an apartment situation.''

Ms. Nguyen, who lived in the Bronx for 20 years, had no family members left to bury her. As such, her union, 1199/S.E.I.U., which represents health care workers, said that it would pay for her funeral and arrange a memorial service.

Federal investigators were still awaiting the results of a handwriting analysis comparing the writing of a Hamilton Township, N.J., man to the three anthrax-laden letters postmarked in Trenton.

On Monday, F.B.I. agents questioned two men who lived at the Greenwood Village apartments in Hamilton, about three miles from the postal facility where the letters were postmarked. Investigators questioned the men, then took them into custody after they gave answers that one law enforcement official described as evasive. The next day, the authorities returned and searched their apartment, removing several bags of items. Authorities said the men had not been charged, but that they were being held for questioning by officials from the Immigration and Naturalization Service.

By JANE FRITSCH
Published: November 10, 2001

A federal judge yesterday refused a request by the New York Metro Area Postal Union to shut down the Morgan Processing and Distribution Center. In late October, anthrax was found in four high-speed mail-sorting machines at the station, at 29th Street and Ninth Avenue.

The judge, John F. Keenan of the United States District Court in Manhattan, denied the union's request for a preliminary injunction, saying union lawyers had not shown there was a likelihood of ''irreparable harm.''

Postal authorities insist the facility has been adequately cleared of anthrax spores, and is safe for workers.

Judge Keenan ordered the Postal Service to test the nearby James A. Farley Building for anthrax spores, however. Tests have already been conducted at five postal stations in New York, including Morgan, which is connected to the Farley station by a tunnel.

William M. Smith, president of the union, which sought the injunction, criticized Judge Keenan's decision not to close the Morgan Station. ''Morgan is still absolutely dangerous,'' Mr. Smith said. ''He should have closed it.''

In New Jersey, the authorities announced that tiny amounts of anthrax had been found in four small post offices that had served as feeder offices for the Hamilton Township center that processed at least three anthrax-laced letters in September and early October. None of the four offices was ordered closed, and officials believe the contamination resulted from cross-contaminated mail that had traveled between the offices and the Hamilton center.

And in New York, a spokeswoman for The New Yorker magazine said health officials were investigating whether an editorial assistant who handles mail had been infected with anthrax in late September. The employee had developed a skin lesion, but tests done at the time did not confirm anthrax infection. The city Health Department said further tests completed last night also came back negative. But as a precaution, the department said environmental sampling would be done at the magazine's offices to determine whether anthrax spores are present.

The judge's ruling concerning the Morgan center came after days of hearings on the building's safety. Dr. Stephen Ostroff, an epidemiologist from the federal Centers for Disease Control and Prevention, testified that the risk of contracting anthrax from the contamination at the center is ''basically negligible . . . close to zero.'' He said the peak risk period at Morgan was mid- to late September, shortly after contaminated mail passed through the facility.

Postal authorities have said they believe that Morgan was contaminated by anthrax-tainted letters sent from New Jersey and processed at Morgan before being delivered to NBC and The New York Post in September.

In New Jersey, Dr. Eddy A. Bresnitz, the state epidemiologist, said that in sampling at the 49 offices served by the distribution center in Hamilton Township, one sample from each of four separate offices were positive. That brings to seven the number of postal facilities where anthrax spores have been detected since three letters containing spores were mailed from the Trenton area.

Dr. Bresnitz said the positive samples were taken from the Rocky Hill, Princeton Palmer Square, Jackson and Trenton Station E post offices. He said that postal workers were at ''very low risk'' from the trace amounts detected and that none had become ill.

Vito Cetta, the post office's district manager for central New Jersey, said the four offices, with 80 to 90 workers each, would be cleaned tonight.

Upon learning about the findings, the nation's largest postal union, the American Postal Workers Union, demanded that the four postal stations be closed until they were thoroughly cleaned.

Jim Burke, eastern regional coordinator of the union, said, ''Our position is that if there is any contamination, we want the place evacuated until it's cleaned.''

Mr. Burke said his union was debating whether to go to federal court to close the stations.

City officials yesterday announced that they were going to be conducting, in coordination with the C.D.C., testing of New York City subways over the weekend. Sampling will be focused in an area where Kathy T. Nguyen, the Bronx hospital worker who died of anthrax last week, was thought to have taken the subway during her commute from her home in the South Bronx to her stockroom job at the Manhattan Eye, Ear and Throat Hospital on the Upper East Side.

A team of about 10 C.D.C. and health department officials will be looking in particular at air vents and air filters in the part of the subway system Ms. Nguyen used. There was a possibility they will be examining other stations as well. But they said they had no reason to believe subways had been contaminated.

''It's just out of the excess of caution,'' said Mayor Rudolph W. Giuliani at a news conference yesterday.

Correction: November 13, 2001, Tuesday Because of an editing error, an article on Saturday about anthrax testing and cleanup at post offices in the New York region misstated the number of employees at the four offices in New Jersey where anthrax was found. It is 80 to 90 in total, not apiece. 

By NICHOLAS WADE
Published: November 10, 2001

A cardiologist in New Jersey said yesterday that he thought he might have contracted skin anthrax in the first week of September.

Should the case of the cardiologist, Dr. Gerald M. Weisfogel, turn out to have been anthrax, it would be of considerable interest to investigators. It precedes the first batch of anthrax letters that was sent out on or around Sept. 18 and would indicate a new and earlier source of exposure.

The federal Centers for Disease Control and Prevention agreed Thursday to test Dr. Weisfogel's blood for antibodies to anthrax toxin but said it did not expect results in the next few days.

In an interview, Dr. Weisfogel, who has since recovered, said he believed at first that he had a spider bite and treated himself with antibiotics. He picked off the black scab that formed on his skin, and the wound eventually healed. Only recently did a biologist friend suggest that his case might have been anthrax and persuade him to get his blood tested.

Cases of cutaneous anthrax in New York were initially diagnosed as spider bites. Reading the clinical description of one of the cases, Dr. Weisfogel decided that his was ''an exact mirror.''

There were other factors that made him decide it would be worth testing the possibility. One of his offices is in Kendall Park, next to Franklin Park, the town cited in the return address on the anthrax-laden envelope sent to the Senate majority leader, Tom Daschle, on Oct. 9.

Dr. Susan Goldstein, a C.D.C. employee who is now working at the New Jersey Department of Health on the anthrax attacks, said a sample of Dr. Weisfogel's blood was on its way to the agency's headquarters in Atlanta to be tested.

''The description he gave could have been a lesion compatible with anthrax,'' she said.

Dr. Weisfogel said he had continued to feel ill after the skin lesion resolved itself and he checked into John F. Kennedy Hospital in Edison on Oct. 20. Doctors there gave him a diagnosis of spinal meningitis and treated him with doxycycline, an antibiotic that is also recommended for anthrax.

Dr. Weisfogel said he was persuaded to get his blood tested for antibodies to anthrax, a sign of past exposure to the bacterium, by a distant relative, Dr. Henry Niman, a molecular biologist who now works at NetCog, an online financial newsletter, and has taken a keen interest in the anthrax scare. At first the C.D.C. office in New Jersey declined to test his blood, Dr. Weisfogel said, on the grounds that his case had occurred before the first known mailing of anthrax and that he had no connection with the postal system. The office also told him, he said, that a positive result would be meaningless because the current blood test, though highly sensitive to anthrax, also gave many false positives. After further discussions the office agreed on Thursday to undertake the test.

Dr. Goldstein did not comment on his assertions other than to say that Dr. Weisfogel's call was treated the same as other calls her office received.

Anthrax experts said it was too early to tell much from Dr. Weisfogel's account of his case. Dr. Morton N. Swartz, an expert on anthrax at the Massachusetts General Hospital, said that he ''wouldn't jump to the conclusion it's anthrax'' on the basis of Dr. Weisfogel's description alone because there could be many other explanations.

Dr. Philip Brachman of Emory University, who has studied anthrax for many years, said that the patient usually notices a blister first and, after it bursts, a depressed black scab known as an eschar. Dr. Weisfogel said the first thing he had noticed was a blackened area that later developed into a depressed scab.

''If I had to say yes or no,'' Dr. Brachman said about the possibility of anthrax, ''I'd say no.''

Linda Vizi, a spokeswoman for the Federal Bureau of Investigation in New Jersey, said word of the doctor's possible infection had not reached law enforcement authorities.

''But if it is confirmed,'' she said, ''we'll give it the full-court press.''

For weeks, federal investigators have been tracking mail routes, interviewing pharmacists and surveying universities and other institutions in their search for leads on who might be behind the anthrax attacks. 

By LAWRENCE K. ALTMAN, M.D.
Published: November 13, 2001

About 3 a.m. on Oct. 12, Dr. Jeffrey P. Koplan, director of the Centers for Disease Control and Prevention, awoke to a call from one of his top epidemiologists, Dr. James M. Hughes, who said, ''We've got something reported from the lab, and we need to look at it.''

A few minutes later, Dr. Koplan, Dr. Hughes and a pathologist, Dr. Sherif R. Zaki, were peering through a microscope at a specimen of skin from an employee of NBC in Manhattan, who was suspected of having cutaneous anthrax.

It was just what the centers had been on alert for since an anthrax case had been detected in Florida a week earlier. The events that unfolded in these early hours would lead the C.D.C. to embark on the largest epidemiologic investigation in it history, covering more than 50 years.

As the medical detectives met, they had only the bit of skin to test. The question of whether the NBC employee, Erin O'Connor, had anthrax -- and thus, whether terrorists might have spread anthrax spores in New York City -- now depended on an immunological and chemical test that Dr. Zaki had developed a few years before.

''We knew we were going to be subject to incredible scrutiny,'' Dr. Koplan recalled, especially since they had no powder, no suspicious letter or other evidence. Nor had they tested a culture, the preferred, but slower, method of determining anthrax.

''But,'' he said, ''we have enough confidence in Dr. Zaki to say, 'If he says it, we'll go with it.' ''

About 3:30 a.m., after Dr. Zaki had finished explaining his findings, ''we walked away convinced,'' Dr. Koplan said. Ms. O'Connor probably had anthrax. The C.D.C. doctors informed the New York City Health Department's top epidemiologist, Dr. Marcelle Layton.

A few hours later, Dr. Koplan was on the phone with Mayor Rudolph W. Giuliani. ''Are you sure it's anthrax?'' the mayor asked.

''Well, we have a high degree of probability,'' Dr. Koplan replied.

''No, no, no, don't give me that stuff,'' was the mayor's rejoinder. ''Is it anthrax or is it not?''

''Yes,'' Dr. Koplan said.

''Fine, that's all I needed to hear,'' Mr. Giuliani said.

In the following days, Dr. Koplan pulled together the largest epidemiological force the disease centers had ever marshaled. As the investigators learned about cases at other news media companies and among postal workers, they worked to check out suspected and confirmed cases in New York City, New Jersey and the District of Columbia. The work went on around the clock; some investigators napped briefly on cots set up in offices; others went home only for quick showers. One epidemiologist postponed her wedding to join the investigation.

The effort was huge, but for many doctors, especially in the early stages, it was not enough.

''We needed concrete recommendations about how to handle situations,'' said Dr. Daniel Ein, a physician in Washington and the former president of the city's medical society. Instead, he said the early stages of the investigation were plagued by confusion and conflicting information.

When he called the disease centers' hot line, he said, he ''talked to some fellow who might have had a high school education and he was fumbling around,'' unable to answer Dr. Ein's questions.

It was days before things were running more smoothly.

Since its creation 50 years ago, the centers' Epidemic Intelligence Service has built a worldwide reputation for solving puzzling cases and outbreaks. Because these medical detectives have learned that early detection is vital to effective control and prevention, they often concentrate on finding cases in the earliest stages, even if it means focusing on just a few cases.

Although an unusually large team of 15 epidemiologists and laboratory scientists was sent out when the initial anthrax case was reported in Florida on Oct. 4, the investigation started in the traditional mode, with the assumption that the disease had natural causes, Dr. Hughes said.

The approach changed abruptly with the early morning call to the New York City Health Department. In part because no one knew how widespread the attack would be, the centers dispatched dozens more scientists to New York, assigned more than 500 of its 4,000 employees in Atlanta to the anthrax outbreak and made plans to enlarge the group if needed. Epidemiologists who had been working on influenza, diabetes and tobacco control suddenly found themselves investigating anthrax. 

''It was clear that we were going to have to operate differently'' to deal with the immediate and potential threat, Dr. Hughes said.

Within hours of the New York call, Dr. Koplan's team had converted a large room into an operations center and installed telephones and computers.

Partitions separated the staff into different teams, called pods. One pod was set up to communicate with investigators in the field. A second dealt with health officials in the states with confirmed cases. A third communicated with health departments in other states where officials were investigating suspected cases and hoaxes. Conference calls with state health officials were held frequently. More staff members were sent into the field as needed.

At the same time, a fourth pod tried to help laboratories that had been overloaded with requests for testing, helping them obtain supplies and reporting back to them about specimens they had sent to the C.D.C. laboratories.

The agency summoned additional experts on plague and tularemia from its laboratories in Fort Collins, Colo., out of concern that terrorists might launch attacks with these and other infectious agents, Dr. Hughes said.

And additional pods were set up to help with suspected cases in postal workers and in other countries, to deal with public relations and to determine the best ways to detect and treat anthrax.

Meanwhile, the centers were changing in other ways. With the anthrax attack, the C.D.C. imposed the tightest security measures in its history, surrounding buildings with the concrete barriers that have become familiar at government centers around the country.

Meetings go on constantly, punctuated by cellphones' ringing as field workers call in to consult with colleagues. About 40 leaders from the pods and top officials of the disease centers met twice a day, at 9 a.m. and 4 p.m., to report the latest findings. In addition, there are telephone briefings to officials of the National Security Council and the C.D.C.'s parent agency, the Department of Health and Human Services. Last Thursday, President Bush became the first president to visit the disease centers while in office.

Communication links between Dr. Koplan and Health and Human Services Secretary Tommy G. Thompson are open, and Dr. Koplan said he had been able to reach his boss at any hour.

But in the initial stages of the inquiry, communication among team members was difficult because some epidemiologists in the field were not privy to information gathered by colleagues, said Dr. Marc S. Traeger, an epidemiologist from the disease centers, who was assigned to the Florida health department. Sometimes, he said, the medical investigators learned key information through news reports.

Dr. Traeger said the health investigators were hampered because they were also involved in a criminal investigation that required keeping confidential the type of medical information that is ordinarily released to the public.

''There were directives from higher government levels that determined what we could or could not release, or even sometimes what could be discussed in a phone conference,'' Dr. Traeger said.

When law enforcement officials secured the Florida building where the first anthrax case was detected, the American Media headquarters, epidemiologists and environmental workers were prohibited from entering to collect samples. Instead, the task fell to agents of the Federal Bureau of Investigation. But because they had not been trained to obtain such samples, the agents were directed by scientists outside the building, and the agents ''were very concerned for their own health,'' Dr. Traeger said.

Dr. Traeger urged that health workers and law enforcement officials receive training in each other's disciplines so they could conduct investigations without interfering with the other's roles.

Epidemiologic clues may help track down the criminals. But, Dr. Koplan said, epidemiologists ''are not going to be the people who solve this'' criminal case.

Dr. Koplan said the disease centers would remain on high alert for anthrax. The lull in reported cases ''has little meaning when a criminal act has been performed and someone is out there potentially with the will and the tools to do this again,'' Dr. Koplan said. 

The inability of health and law enforcement officials to find the source of anthrax and identify the terrorists who spread it has ''everyone freaked out,'' said an epidemiologist who is involved in the investigation and who spoke on condition of anonymity.

Agency officials acknowledged such tensions, but attributed them to the sense of urgency in the investigation. ''Any time you can't get to the bottom line, there's an understandable sense of frustration, but that does not deter us from aggressive action,'' Dr. Hughes said.

An overriding factor in driving the investigation is pride, the officials said.

''There is a feeling that this is what the place is supposed to be about, that this is the time when we have got to perform and do it well,'' Dr. Koplan said. ''This is the agency at its best.'' 

THE THEORIES
Case in a Small Town Compounds a Puzzle for Epidemiologists
By LAWRENCE K. ALTMAN

Epidemiologists investigating the anthrax death yesterday of Otillie W. Lundgren, 94, from Oxford, Conn., are confronting a mystery as baffling as the case of a Bronx woman, Kathy T. Nguyen, who died on Oct. 31 leaving no clue to the source of her infection.

The puzzle is how Mrs. Lundgren, a woman in her 90's who lived alone, walked with a cane and had limited contact with the world outside her home could have come down with inhalation anthrax. Anthrax has been rare in Connecticut; since 1950, the state has reported just one case, and that was the skin form involving a male mill worker in Glenville in 1968.

Even though Mrs. Lundgren seemed an unlikely anthrax patient, her doctors at Griffin Hospital in Derby, Conn., started acting on recommendations from the Centers for Disease Control and Prevention for multiple drug treatment as soon as they had a hint that she had the infection on Saturday, a day after she was admitted to the hospital.

The doctors told her she might have anthrax and asked about her activities. She told them she had noted nothing unusual about her mail, did not garden, and could shed no light on the possible source, said Dr. Kenneth Dobuler, chief of medicine at Griffin Hospital. The hospital did not notify the state's Public Health Department about her case until Monday, so epidemiologists were unable to interview her before she died.

Now, as epidemiologists talk to her family and friends to learn about her activities and who she encountered over the six weeks before she became ill, they will try to fit what facts they glean into the accepted wisdom about the bacterial infection.

In contending with the first known deliberate spreading of anthrax spores in history, the authorities have found that the accepted wisdom of medical texts has been challenged on several fronts.

As they examine the puzzling cases of Mrs. Lundgren and Ms. Nguyen, federal health officials wonder:

What is the smallest number of spores that can cause anthrax?

Does it take fewer spores to infect an older person than a younger one?

How often have anthrax cases, particularly in older people, gone undetected because they were diagnosed as pneumonia?

How often can anthrax spores be found in areas where cases have not been reported for many years?

Mrs. Lundgren's strain of anthrax matches that of the other 18 confirmed cases, said Tom Skinner, a C.D.C. spokesman. It will be later this week before scientists learn whether spores were present in her home, which investigators tested Tuesday. The medical detectives are also looking for evidence of contamination in her mail.

Anthrax spores can survive for decades and they are commonly found on ranches where it has killed cattle. But scientists have not conducted surveys to determine how often anthrax spores can be found in the ground, homes or office buildings in Connecticut or elsewhere in the country.

It may take a smaller number of spores to produce inhalation anthrax in a 90-year-old person than in a much younger person if their immune system had been weakened by age or if the debris collected in years of breathing had damaged the cells that whisk particles away from the lungs, said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases.

An average of 8,000 to 10,000 spores are needed to cause death from inhalation anthrax in animals.

But no one knows the minimal number it takes to cause infection in a human, said Dr. James M. Hughes, who oversees C.D.C.'s investigation into the anthrax outbreak as head of its infectious diseases center.

Dr. Jeffrey P. Koplan, director of the disease centers, said yesterday that it was unlikely that Mrs. Lundgren was infected naturally, but that epidemiologists would have to keep an open mind and explore all possibilities. Among the considerations is the possibility that her infection came from contamination of some medication she took.

Inhalation anthrax has been rare in this country, with only 18 cases reported since 1950. Dr. Koplan said it was unlikely that many cases of inhalation anthrax were missed in the past, but he added "it's conceivable that our heightened surveillance" in recent weeks has detected cases that might previously have gone undetected.

Connecticut is one of the states involved in a network that C.D.C. created about six years ago to investigate unexplained deaths, and that program has not turned up any cases of anthrax, Dr. Hughes said.

Doctors in Derby were astonished when Mrs. Lundgren -- whom they had admitted to the hospital out of concern that she had become slightly dehydrated by what appeared to be a mild respiratory infection -- became the country's fifth death from anthrax since early October.

When a relative drove Mrs. Lundgren to the hospital late Friday morning, she supplied her own medical history. She had a mild cough, was a little short of breath, and had a temperature of about 102.3 degrees Fahrenheit, Dr. Dobuler said. A number of tests, including a white blood count (that can rise with a bacterial infection) and a chest X-ray, were normal.

Because they suspected she had a viral infection, doctors did not prescribe antibiotics until Saturday when all four cultures of her blood grew microbes that resembled Bacillus anthracis. Hospital microbiologists performed more tests on Sunday and determined that it was the anthrax bacillus, not one known as B. cereus that can be a contaminant from the skin and with which B. anthracis can be confused.

Mrs. Lundgren's condition remained stable Saturday and Sunday, and she talked readily as her condition remained stable. But during that time the doctors did not ask her about exposure to animals and other epidemiologic factors related to anthrax.

On Monday, as Mrs. Lundgren's condition deteriorated rapidly, her chest X-ray became abnormal, but it did not show the characteristic widening of the mediastinum, the space between the lungs that is typically expanded by swollen lymph nodes when they are infected with anthrax, Dr. Dobuler said. The hospital notified the health department, which performed additional tests to identify the microbe as B. anthracis.

Final confirmation came early Wednesday morning from a polymerase chain reaction test performed on samples sent to C.D.C. in Atlanta. The test can theoretically detect a single microbe in a sample.

C.D.C. has sent a team of 17 epidemiologists, environmental health specialists and other scientists to Connecticut to investigate Mrs. Lundgren's case.

"Do we have any insight where her anthrax came from?" Dr. Fauci said. "No."

He continued: "But the possible light at the end of the tunnel is that unlike Kathy Nguyen, about whose movements we know very little, Mrs. Lundgren was housebound and when she did go out, she always went with one or two friends. So under those circumstances it might be much easier for law enforcement authorities and epidemiologists to really track every place she has been over recent weeks. If there is a clue there, hopefully they will find it."

By LAWRENCE K. ALTMAN, M.D.
Published: December 4, 2001

Is anthrax really as rare in this country as experts believe? Given the resemblance of its early stages to other ailments -- skin anthrax can look like a spider bite or acne, and the inhaled form like a viral respiratory infection -- many people have wondered whether other cases may have occurred in the past, unrelated to terrorism, and been misdiagnosed.

Until the intentional spread of anthrax in recent months, only 18 cases of inhalation anthrax had been reported since 1950, and 227 of the skin form from 1955 to the beginning of the intentional spread this fall. Additional anthrax cases may have gone undetected over the years, but the number would be small, infectious disease experts said in interviews.

''No matter how I think about this, I doubt that we would miss more than the rare, rare, rare case,'' said Dr. David Gilbert, the president of the Infectious Diseases Society of America.

''I am sure we can come up with some extenuating circumstances where patients have slipped through the system, but it is very unlikely that we've missed lots of cases'' because the illness is so striking, said Dr. Gilbert, who practices at Providence Portland Medical Center in Oregon.

No one knows the precise number. Since the death of Ottilie Lundgren, 94, on Nov. 21, federal and state epidemiologists have scoured medical records in hospitals and offices in Connecticut for clues to missed cases and turned up none.

Still, widespread publicity about the recent outbreak unquestionably led doctors to diagnose anthrax in some cases that they otherwise would not have detected because they have had so little direct experience with the infection.

One such case is that of a 7-month-old boy in Manhattan, who is thought to have contracted the infection when his mother, an ABC news producer, took him to work on Sept. 28. The child nearly died from skin anthrax in October.

The boy's physician, Dr. William Borkowsky, a pediatric infectious disease specialist at New York University, said he made a point of studying anthrax when bioterrorism became a threat in recent years. Even so, Dr. Borkowsky said he would have diagnosed the infant's lesion as a spider bite if he had not known that anthrax was present in New York City.

The reason is that when Dr. Borkowsky first examined the infant's skin lesion on Oct. 2, tests showed no evidence of anthrax. The infant also suffered kidney damage, bleeding and a type of anemia that rapidly destroyed red blood cells and required four blood transfusions.

''The syndrome this child had had never been described in anthrax'' but had been linked to spider bites, Dr. Borkowsky said. ''The skin lesions were compatible with anthrax, but the rest of the picture was incompatible because we reviewed all published cases of anthrax dating to the 1950's and never found the particular blood problem, microangiopathic hemolytic anemia, linked to anthrax in an adult or a child.''

But as soon as Dr. Borkowsky learned about the first cutaneous anthrax case in New York City on Oct. 12, he said he called an official of the New York City Health Department and also sent an e-mail message describing the case. But he received no reply.

Frustrated, Dr. Borkowsky then called another branch of the Health Department, the Poison Control Center, which was handling calls for suspected anthrax. But he had trouble finding an official who knew about anthrax.

Eventually, Dr. Borkowsky spoke to Dr. Farzad Mostashari, an epidemiologist assigned by the Centers for Disease Control and Prevention to the New York City Health Department, who examined the child that night. Dr. Mostashari said the infant's lesion looked exactly like the one that he had seen four hours earlier in Erin O'Connor, 38, the first recognized anthrax victim in New York City.

Dr. Borkowsky had frozen some of the child's blood with the intent of testing it later for evidence of a spider bite. Instead, the doctors used the blood to confirm anthrax.

It took a month for the child's kidneys to regain normal function, Dr. Borkowsky said, and now he is fine. 

In reflecting on the case, Dr. Borkowsky said that if he had not learned about the presence of anthrax in New York City, he would have diagnosed a spider bite because the baby's symptoms were ''so atypical of what I was expecting for anthrax.''

Milder cases of skin anthrax may have gone undetected because they can be cured by antibiotics, even if the drugs are prescribed for some other reason. Also, skin anthrax can heal on its own and even resemble bad acne.

In comparison, inhalation anthrax progresses much more swiftly and strikingly than skin anthrax. Yet there are disquieting signs that some cases may have been missed because of recent changes in medical practice and education that have made doctors less vigorous in pursuing a diagnosis at the bedside or in a microbiology laboratory. These changes began even before managed care affected the economics of medical practice and teaching, and have accelerated since.

''It is possible that a fluke case or two of inhalation anthrax over the years, not every year, could have gone undetected,'' said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases. ''But we have not missed six or seven cases a year.''

''When these people get overwhelming sepsis associated with inhalational anthrax, it is tough to miss, even when you are not thinking about it,'' Dr. Fauci said.

Referring to a laboratory test known as the Gram stain that can help detect Bacillus anthracis, Dr. Fauci said: ''It is not easy to miss these horrible looking Gram positive rods that look like boxcars. They are very striking'' and can be found in blood cultures even when patients seem healthy.

Dr. Fauci cited the case of a man who walked into a hospital with just mild intestinal symptoms and no fever; blood cultures yielded enormous numbers of anthrax bacilli.

But doctors must order such tests before the microbes can be detected, and whether they do depends on how hard they and the microbiology laboratory are willing to look. The initial culture may not distinguish B. anthracis from bacteriological cousins that are common skin contaminants, and laboratories often discard such cultures without precisely identifying the bacillus.

Because immune function tends to wane with age, older people seem to be more susceptible than younger people to infection from the same microbes. Yet doctors tend not to investigate pneumonias in the very old as thoroughly as they do in younger people. So some cases of inhalation anthrax may be missed in old people.

''If it weren't for the recent number of cases, and I had a 90-year-old lady who came in with fulminant pneumonia, and she had a Gram positive rod in her sputum, I would assume it was a bacillus contaminant species and would not have pursued it,'' and neither would many other doctors, said Dr. Marvin Turck, the editor of The Journal of Infectious Diseases.

''We have a lot of similar cases,'' said Dr. Turck, who is a professor of medicine at the University of Washington. He also said: ''It would be an inappropriate way of using resources if every laboratory tried to identify every bacillus species on every sputum. But having said that, I still don't know how prevalent anthrax is in the community, though I know it is not a large number.''

The traditional, standard practice was to obtain sputum and other secretions from patients with suspected pneumonia and other respiratory infections so cultures could be started before antibiotics were given.

But doctors now often do not obtain cultures from patients with suspected pneumonia or other conditions before prescribing antibiotics. In selecting the antibiotics, doctors often use a shotgun approach and use drugs that will treat a broad array of microbes, including the classical ones, like pneumococci, and atypical ones, like B. anthracis, Dr. Turck said.

Dr. Joseph S. Pagano, emeritus director of the Lineberger Comprehensive Cancer Center at the University of North Carolina, said recent changes in practice might lead to undetected anthrax cases. Dr. Pagano said that earlier in his career, when he was an infectious disease expert, he would have been reprimanded ''if I ever dared to put somebody on antibiotics without first obtaining a culture and making a diagnosis because that approach makes you less likely to miss something real important.'' 

Dr. Pagano also said he ''deplored the idea of giving a patient antibiotics for a fever without even having an idea about the possibilities that might be causing it.''

''But that type of sharp diagnostic thinking hardly goes on anymore,'' in part because doctors tend to be impatient about going through the process, Dr. Pagano said.

Dr. Turck, of the University of Washington, said that even when doctors in teaching hospitals obtained appropriate cultures, the particular cause of many pneumonias was not identified. Most pneumonias are assumed to be the result of pneumococcal bacteria, Dr. Turck said, ''but about half the time you do not prove any specific microbe as the cause.''

One reason is that even in the best hospitals the sputum that is collected for testing often is mostly saliva from the mouth and not secretions from the lungs, making it difficult to be sure the offending microbe is present in the sample, Dr. Turck said.

Correctly detecting the cause of an infection often requires diligence, shoe leather epidemiology and some luck.

For example, an outbreak of skin diphtheria affected more than 1,100 people in the skid row population of Seattle from 1972 to 1982. The first cases were detected ''only by chance because the skin lesions did not respond to the antibiotics initially given,'' said Dr. Turck, who was an author of a scientific paper reporting the outbreak.

For other infections, outbreaks were caused by previously unknown microbes. Two examples are Legionnaire's disease in Philadelphia in 1976 and hantavirus pulmonary infection in New Mexico in 1993. Subsequent research showed that both microbes had caused illness that was attributed to other conditions in the past.

Inhalation anthrax causes bleeding and swollen lymph nodes in an area behind and between the lungs known as the mediastinum. The damage is so distinctive that pathologists would quickly detect them in an autopsy. But with a striking decline in the number of autopsies performed, such damage could easily escape detection.

Dr. Gilbert, the infectious diseases society president, said that although ''it is worrisome that we don't do as many autopsies as we used to do in people that die with unidentified illnesses, the reason we don't do autopsies is that our pre-mortem diagnostic capabilities are so, so much better.''

Nevertheless, studies have shown that such diagnostic tests often fail to detect serious conditions during life.

Reflecting on the changes in practice, Dr. Pagano said, ''Maybe one of the good things that could come out of this is that infectious disease physicians will sharpen their thinking, realize the need to go back to basics and devote more time to avoid missing a rare case.''

By ERIC LIPTON AND KIRK JOHNSON
Published: December 26, 2001

There was no commotion, no outcry. Except for the blond woman in the black dress sitting by herself in a back pew, no one knew that anything unusual had happened.

Johanna C. Huden, a 31-year-old editorial assistant at The New York Post, had first noticed the strange blister on her right middle finger the day before, Sept. 21. She had not thought too much about it; surely it was just a bug bite or a cat scratch.

Now, though, as she sat in the Long Island church, half-distractedly watching the wedding ceremony, the finger began to itch. She reached down and rubbed it gently against the coarse linen of her dress. Suddenly, a watery white liquid bubbled out across the cloth.

''Ee-yew,'' Ms. Huden recalls saying to herself. ''That is just really bizarre.''

The conventional understanding of America's first-ever anthrax attack says Ms. Huden was a bit player -- a victim of skin, or cutaneous, anthrax who fully recovered and got on with her life. As anthrax spores spread through the mail, and events blurred across six states and the District of Columbia, hers became no more than a name in the middle of a long list of victims.

Yet the conventional understanding is wrong. In the light of hindsight, scientists can now see that the outbreak actually began that September afternoon.

Ms. Huden was the anthrax index patient -- the pivot point upon which every outbreak investigation is based, the crucial clue that every medical investigator hopes can be found, and fast. But on that muggy day at Mary Immaculate Church, she suffered her mysterious wound very much alone.

No one knew.

Those words have become the theme of the medical investigation of the anthrax attacks, a refrain of epidemiological regret.

Certainly, the medical investigators have done much to contain the outbreak and save lives. Yet the inside story of that inquiry -- pieced together from interviews with many of the lead investigators and other health-care officials -- is also a tale of missed cues, misread evidence and erroneous assumptions that led scientists and decision makers to misjudge the threat to postal workers and, through the mail system, to the American public.

For weeks, primary-care doctors individually struggled to diagnose a disease they had never seen and never imagined they would see. In that uncertainty, medical investigators could never quite discern the sequence of infection that began with Johanna Huden. And only through the bitter experience of 5 deaths and 18 other confirmed or suspected cases did they learn how much they did not know about how anthrax spores traveled and infected their victims.

Of course, the medical inquiry is just one of several intertwined strands of the government's still unresolved investigation of the attacks. In recent weeks, in fact, the other aspects have taken center stage, as microbiologists try to pinpoint the nature and source of the mailed anthrax and criminal investigators search for a suspect.

But underpinning those efforts, at every point, are the epidemiologists, the medical detectives on the ground, tracing how the infection spread and whether the underlying pattern of cases can offer up some revelatory clue from the haze.

They can see now that Johanna Huden arrived first in that place of fear and fog. For weeks after the wedding, despite repeated visits to doctors and emergency rooms, her infection worsened and the cause of her illness was missed. And no one knew.

Florida
A First Case To Investigate

Every disease outbreak tells a detective story. The epidemiologist's job is to piece together the narrative threads -- to work back to the beginning and so hasten the end.

Assume nothing; let the evidence speak for itself. That gumshoe credo was very much on Dr. Bradley A. Perkins's mind as the chartered jet roared toward South Florida on the afternoon of Oct. 4, carrying his 12-member team from the Centers for Disease Control and Prevention in Atlanta.

Dr. Perkins, a boyish-looking 42, chief of the centers' special pathogens branch, sat at a small conference table, chatting with the adrenaline-pumped scientists and passing around the latest papers on anthrax. But mostly he tried to concentrate on telling himself not to think about terrorists.

Everyone at the centers, of course, had been worrying about just that since Sept. 11 -- planning for attacks of everything from sarin gas to smallpox to anthrax, perhaps the most widely developed bioweapon in history. But at that moment, all anyone knew was that a tabloid newspaper editor named Robert Stevens was dying of inhalation anthrax in a Palm Beach County hospital. 

Perhaps Mr. Stevens had been infected deliberately -- the first periscope glimpse into a mass bioterror attack. Perhaps. It was also possible that the bacteria had been picked up naturally, from a sick cow, even one long dead; anthrax spores could lie dormant in the ground for decades.

For now, this was just a medical case, though Dr. Perkins knew well that on his word a huge criminal investigation would be unleashed. The fear of being wrong was intense. ''You don't pull the bioterrorism trigger lightly,'' he would say later.

Let the evidence speak for itself. That's how epidemiology had always worked. It was a rhythm of science, intuition and observation -- an art essentially unchanged since the 1850's, when a doctor named John Snow stunned the medical world with the insight that every family with cholera in his London neighborhood drew water from the same pestilential well.

Dr. Snow took off the well's pump handle and became a legend. His cholera-cluster maps became the motif of a new science, premised on the belief that disease, in the dawning age of the germ theory, could be chased from the shadows of superstition and hunted to the ground.

Now, flying to Palm Beach, Dr. Perkins and his team planned the hunt for the handle of this latest pump. They would meet with county health officials, then fan out, testing as they went -- Mr. Stevens's home, office, whatever made sense -- with swabs that would pick up any errant anthrax spores.

By the time they landed, Dr. Perkins felt satisfied that he had pushed as hard as he should the admonition to leave no stone, quite literally, unturned.

But then, leaving the airport, he saw something that tested his assumptions all over again. Flight Safety International, the pilot school where some of the Sept. 11 hijackers were thought to have trained, had a flight simulator right at the airport. Could it be coincidence that here, of all places, and now, of all times, anthrax would just happen?

As he drove his rental car past the building, he had more or less the same thought that had flickered across Johanna Huden's mind two weeks before.

''This is weird,'' he said to himself.

The Northeast
Though Unreported, Patients Accumulate

Actually, up North, seven people were already mysteriously ill.

Teresa Heller, a letter carrier assigned to West Trenton, N.J., had checked into a hospital with an infection on her arm.

Richard Morgano, a maintenance worker at the mail distribution center in nearby Hamilton Township, had a similar lesion on his arm.

In Manhattan, the infant son of an ABC news producer was in a hospital, gravely ill with a high fever and an ulcerated arm.

Erin M. O'Connor and Casey Chamberlain, assistants to the NBC News anchorman Tom Brokaw, had skin lesions -- Ms. O'Connor on her collarbone, Ms. Chamberlain on her leg.

Claire Fletcher, a CBS News aide, had two small infected pimples on her face.

And Johanna Huden had been to two emergency rooms and seen more than half a dozen doctors. Ultimately, on Oct. 1, a surgeon at New York University Medical Center had cut the dead skin out of her finger. Ms. Huden left the hospital with a large bandage on her hand but no better idea of what had made her sick.

None of those cases -- misdiagnosed and misunderstood -- were reported into the medical surveillance system on which epidemiology depends.

Without realizing it, Dr. Perkins and his team were starting in the middle. The Stevens case, they believed, was the index case. And that misperception was the first of many to guide the investigation -- in Florida and then up North -- in the coming days.

The next morning, Oct. 5, the scientists fanned out, checking things ;ole the vacuum-cleaner bags in Mr. Stevens's house and the ventilation system on the roof of the American Media International building, where he worked.

They went to a store where he bought spices in bulk; the store kept live animals, they had been told, and had to be checked as a possible source of natural contagion. They visited his favorite fishing hole and traced his Sunday bicycle route. A separate team went to North Carolina, where Mr. Stevens had first felt ill while visiting his daughter. 

All trails led nowhere. The dead-cow vector, even as a remote hypothesis, faded. Mr. Stevens died that day, unable to help them.

Various pieces of evidence, though, eventually pointed toward the company's mailroom. Tests of a mailroom worker, Ernesto Blanco, hospitalized with a still-undiagnosed illness, turned up an anthrax spore in his nasal passage. Spores were also found on Mr. Stevens's computer keyboard.

But when the investigators first arrived in the mailroom late on the afternoon of Oct. 5, they realized to their horror that, in their exuberance or thoroughness, they had used up all but one of their cotton swabs.

One small swab to test the whole room -- it seemed like the wildest shot in the dark.

So the scientists stood amid the postage meters and scales and argued the point: Though they could get more swabs, this was it for the day, and at a time when every hour felt laden with portents and pressures, the decision seemed enormous. Finally, they decided to use the last swab on a bin holding letters and packages for the photo department, where Mr. Stevens had worked.

The results came back the next day with a direct bull's-eye. The mail bin was heavily contaminated, and the conclusion, Dr. Perkins said, was unmistakable: Mr. Stevens had been the victim of a criminal act.

The finding sent a shock wave through the nation and changed everything about the case. This was not simply a medical investigation anymore. The F.B.I., which, like the disease control centers, had been preparing for bioterror attacks since Sept. 11, took over.

For the epidemiologists, the discovery was as if a fog had lifted just long enough to see that they were headed out into uncharted, and uncomfortable, territory. They were not just hunting an organism with genes and biological logic that could be tracked the traditional way. This was a weapon, deliberately wielded, with an exponentially increasing number of possible sources. That mixture -- the biological and the psychological, the genetic and the perversely pathological -- fundamentally altered the task at hand.

''Usually we're talking about trying to define normal biologic transmission,'' Dr. Perkins said. ''This is a terrorist transmission route.''

Investigators followed that route from the mailroom to the delivery truck, to the Boca Raton post office and through the county's mail system, finding spores all along the way.

What they did not find were any sick postal workers. They had no reason to connect Mr. Stevens to Teresa Heller and Richard Morgano and the others up in New York, because they did not yet know they existed.

The postal system, they now knew, had been used as an instrument of attack, an important finding. But it went only so far. Since no postal workers seemed even remotely affected, the postal connection was treated as one clue among many, not the sure, single pathway suffused with risk.

On Oct. 9, President Bush told an edgy nation that the Florida case appeared to be ''an isolated incident.''

But Dr. Perkins, the epidemiologist, recalls feeling ''extremely uncomfortable.''

''We know someone is out there with the ability to cause disease, but we don't know how much mail is out there or whether the mode of delivery is going to change,'' he recounted. ''We're operating on data that are inadequate for the situation.''

New Jersey
Delayed Recognitions Of Cases Missed

''You heard about Hamilton?''

That was the question Dr. Michael Dash's wife yelled out as he arrived home Saturday afternoon, Oct. 13, on what was to have been a quiet weekend with the family.

She had been checking the headlines on the Internet that afternoon when she happened upon a news bulletin: an anthrax-laced letter had been found in New York that had been postmarked at the Hamilton Township mail-sorting center near Trenton.

''Oh no,'' Dr. Dash thought after reading the story. ''That is what that man had.''

That man was Richard Morgano, 39, a barrel-chested maintenance worker at the Hamilton postal center, who had come into Dr. Dash's New Jersey office on Oct. 1 with a strange infection.

Mr. Morgano had scratched his arm on Sept. 20 while reaching into a Hamilton mail-sorting machine. A blistered wound had formed, oozing a yellowish liquid around back spots of dead skin. His arm was twice its normal size, his lymph nodes swollen and his hand unbendable. 

At that first meeting, Dr. Dash put Mr. Morgano on a strong dose of antibiotics and, after checking a reference book, asked Mr. Morgano a line of questions fearing he was facing a condition he had never before seen.

''You doing any hunting recently? You've been working with pelts? Been around goats or any farms?'' Dr. Dash asked, checking possible natural causes of anthrax.

But Dr. Dash had never imagined that a postal worker in central New Jersey would be the victim of a terrorist attack. So when Mr. Morgano answered ''no'' to each of the questions about natural sources of anthrax, Dr. Dash had ruled it out.

Dr. Dash was far from the only physician who had a sudden and disturbing realization that weekend. The discovery in New York of the anthrax-contaminated letter, which had infected an NBC News employee, evoked a series of calls to local and federal authorities in New York and New Jersey.

In fact, on the same day Mr. Morgano was at Dr. Dash's office, Ms. Huden and the ABC producer's baby were just eight floors apart at the New York University Medical Center.

''I kick myself when I think about it now,'' Dr. Douglas Yoshia, the attending physician on duty when Ms. Huden showed up at the emergency room.

Like Dr. Dash, upon hearing about the NBC case and the Hamilton letter, Dr. Yoshia immediately realized Ms. Huden had had anthrax. But he had one more complication to overcome: He could not remember her name. It took a few days of searching through hospital records to track it down and by the time he reached Ms. Huden, her case was already being investigated.

It was only once these cases bubbled to the surface that the true pattern of the outbreak started to become apparent. And, perhaps most important, health officials now had hard evidence that postal workers were, at a minumum, at risk of cutaneous anthrax.

Even so, the full significance of this discovery was not initially recognized. It took five days to confirm that Mr. Morgano and Ms. Heller, the West Trenton letter carrier, had anthrax.

By Oct. 18, when these cases were confirmed, seven other postal workers -- three in New Jersey and four in Washington -- had begun to feel sick, most with the more serious version of inhalation anthrax. The second wave was under way, this time from poisoned letters postmarked at Hamilton on Oct. 9 on their way to Capitol Hill.

In this wave, a few of the cases would be identified quickly, and the postal employees would recover. But again, some doctors who encountered these sick postal workers would not make the anthrax connection. And this time, the implications would be fatal.

District of Columbia
The Medical Becomes Political

It was still dark and silent that Saturday morning, Oct. 20, when Dr. Michael S. A. Richardson picked up the telephone in the hallway of his Washington townhouse to call the office. During the night, he had received a message on his new cellphone -- issued to go with his new job as an acting senior deputy director at the District of Columbia Department of Health -- but no one had taught him how to retrieve messages.

Now, as he realized what he had missed during the night, he stretched the phone cord into the living room, perched on the arm of a chair and scribbled notes as fast as he could.

A worker at the Brentwood Road postal center in Washington, Leroy Richmond, had been tentatively diagnosed with inhalation anthrax. The implication was staggering.

''We are in the middle of this,'' Dr. Richardson recalled thinking. ''And it's a huge deal.''

Washington is where the anthrax story became political, social, even racial, theater. And it is where the assumptions of the investigation -- woven from decades of conventional scientific wisdom and weeks of evidence and missed cues -- all unraveled.

When he picked up the phone that morning, Dr. Richardson did not know about the second wave. What he -- and the rest of the nation -- did know was that just five days earlier, on Oct. 15, an anthrax-laced letter had been opened in the Capitol office of Tom Daschle, the Senate majority leader. And though reports conflicted, suspicions ran deep -- and had been played in banner headlines -- that the material in this letter was dangerously different. Many of the government's bioweapons experts were saying that the anthrax spores seemed much smaller, perhaps capable of staying airborne longer, and thus far more likely to penetrate deep into the lungs. 

Even so, Dr. Richardson knew of no postal worker who had developed the life-threatening inhaled form of the disease, despite the trail of spores across the postal system. And the disease control agency had said that only people in the immediate vicinity when a poisoned letter was opened were at risk.

Dr. Richardson also knew that an initial test at Brentwood Road, where the Daschle letter had been processed, had turned up no evidence of contamination. And there was the curious case of the worker at the P Street station, who had tested positive for inhalation-anthrax exposure immediately after the Daschle letter, but then, after retesting, was put back on the negative list. Both those results seemed to reinforce the conventional wisdom.

Now it was all dreadfully wrong. Postal workers were in direct and dire danger. Sealed envelopes could leak. The inhalation case at Brentwood had presented, literally overnight, a new signature of threat.

What was clear, too, was that the full implication of tinier, airborne spores had not been thought through; early hints, like the P Street worker, had become missed opportunities rather than signal flares suggesting that more testing might be needed. In Atlanta, it would be another week and a half before the C.D.C. opened what turned out to be a very prescient e-mail -- a warning from Canadian researchers, sent Oct. 4, that tests had shown that anthrax spores could leak through envelopes.

Dr. Richardson has no illusions that an earlier grasp of the dangers of the Daschle anthrax could have kept Mr. Richmond or the three other infected Brentwood workers from getting sick; they had already been exposed. But it might have meant faster diagnosis and faster treatment. With physicians on the alert, the words ''I work for the postal service'' would have opened doors and minds in doctors' offices everywhere.

''Everybody and their mother would have known that a postal worker is potentially at risk,'' Dr. Richardson said. ''And so that famous tape of this man Morris, saying that he went to his doctor and the doctor told him don't worry, would probably not have happened.'' Thomas Morris Jr., a Brentwood worker, died on Oct. 21; Mr. Richmond recovered.

The flawed assumptions had other consequences. Because postal workers had not been considered at risk, only people at the Capitol were tested and given the anthrax antibiotic Cipro after the Daschle letter was opened. Now, Dr. Richardson saw, a huge intervention -- running late and behind the curve -- would have to begin.

And in Washington, where conflicts of race and class simmer even in the best of times, a late start would have its own costs and consequences.

The city's health commissioner, Dr. Ivan C. A. Walks, faced it first-hand when the congregation at an African-American church peppered him with questions about why postal workers, many of them black, were being treated differently than people at the Capitol. While some postal workers ultimately were tested with nasal swabs, the process was stopped, epidemiologists said, because the technique was unreliable.

'' 'The folks on the Hill got swabbed, now you're not swabbing us,' '' said Dr. Walks, who is black, recalling the uncomfortable questioning in the church. '' 'White people got swabs, black people didn't get swabs.' ''

People also questioned the switch from Cipro to doxycycline -- a far less expensive, but equally effective, antibiotic.

''The white folks got Cipro -- we're getting doxy,'' Dr. Walks said, replaying the exchange. ''They got the expensive drug -- you're trying to save money with us.''

It was not just a matter of anger. The shifting understanding of anthrax also created doubt about just how much the epidemiologists should be trusted or believed.

Dr. Richardson saw the doubt that Sunday night, as health officials distributed antibiotics to postal workers downtown. Around 10 p.m., Dr. Richardson was approached by a distraught man who said the disease agency was wrong to believe that only a directly poisoned letter was a threat. The man said he worked at Brentwood and knew how mail got tossed around in the sorting machines. 

You don't know, it's not one place, things get mixed up,'' he said. ''There has to be cross-contamination.'' In other words, even mail that came in contact with poisoned letters might not be safe.

''I had no idea what he was talking about,'' Dr. Richardson said. He told the man to share his information with the C.D.C.

Atlanta
Debating Public Policy At the C.D.C.

The national cerebrum of the anthrax crisis was a small conference room at Centers for Disease Control headquarters plastered with bioterror versions of Dr. Snow's cholera maps. There were detailed floor plans of newsrooms and Senate offices, and now, the shop floor at Brentwood Road, all color-coded to indicate the different paths the spores had traveled.

Most of the room was taken up by a rectangular table with a speakerphone that linked the center's scientists with the other players in the investigation -- the F.B.I., the postal service, the homeland-security bureaucracy and local law-enforcement officials across the nation. The scientists found themselves exercising some unfamilar mental muscles. Dr. Perkins says he thought that a Cliff Notes compendium of fictional bioterror plots would have come in handy.

It was in that conference room, on Monday, Oct. 22, that centers officials began debating what they say were among the most difficult questions the agency had ever addressed: Was the postal system itself contaminated? Should it be shut down? Such a decision, the officials knew, would rip through the economy, not to mention the delicate psyche, of a nation under siege.

''Is there a health hazard here of such a magnitude that it would warrant that type of action?'' asked Dr. Julie L. Gerberding, the centers' acting deputy director of infectious disease, who two decades before had seen the AIDS epidemic emerge in San Francisco.

The magnitude of the anthrax hazard certainly seemed to be growing. Two Brentwood workers had died; two others were in intensive care. In New Jersey, a postal worker appeared to have the state's first case of inhalation anthrax. Four days earlier, state health officials closed the Postal Service's regional distribution center near Trenton.

But there was also a conundrum underlying the debate. In an atmosphere of rising crisis, Dr. Gerberding and others felt huge pressure to act decisively, even as events in Washington had made it clear to them that decisiveness was hardly warranted.

What's more, they were in an unaccustomed, and uncomfortable, position of power. While the agency could only recommend shutting the system down, officials knew their advice would carry great weight. The debate became a test of leadership, science and nerve, all bound together by constant stress and sleepless nights.

Dr. Walks, the Washington health commissioner, who participated in some of the discussions by speakerphone, said it had become hard to discern the line between the need to be confident and the need to be right.

More than once, he said, as he stood alongside public officials at news conferences in Washington in mid-October, he inwardly groaned because old answers about anthrax were still being given and he realized that even information a week or two old could no longer be trusted. Some officials were still saying, for example, that a certain number of spores -- 8,000 to 10,000 was the commonly quoted figure -- were needed to contract inhalation anthrax. Given what was now known about the dangers for postal workers, perhaps that old assumption was no longer true either.

''I think it's time for us to stop needing to say we know and let people know what we don't know,'' he recalled thinking at the time. ''Because if we don't do that they won't believe us when we come to say we know stuff, and that's critical.''

The verdict was to keep the system open -- not because it was deemed clean and uninfected, C.D.C. officials said, but because there simply was not enough evidence of widespread contamination. The finding did little to ease anxieties, though. Closing the system would have affected millions of people; not closing it might, too.

New York
A New Victim. A New Wave?

Dr. Stephen M. Ostroff's darkest hour came sometime before the dawn of Oct. 30. New York, he'd come to believe through a long, sleepless night, was under attack, and as the chief epidemiologist at the C.D.C.'s National Center for Infectious Diseases and the agency's point man for the city, the list of things he didn't know seemed endless.

''It was my worst moment,'' he said.

He had just learned from the city's Department of Health that a 61-year-old stockroom clerk at a Manhattan hospital, Kathy T. Nguyen, was on a respirator and declining quickly from inhalation anthrax. 

Part of Dr. Ostroff's anxiety stemmed from the fact that Ms. Nguyen -- the city's first inhalation case -- fit no previous pattern. The first wave of anthrax-contaminated letters in mid-September had been aimed at news organizations; the second in early October had been sent to political leaders. Was she the sentinel patient of a third wave, focused on the health care system?

But he was also haunted that morning by the long shadow of Washington, and the presumptions that he and other epidemiologists had been so wrong about. Dr. Ostroff had been one of those playing down the threat to postal workers from sealed letters. ''None of us, to our eternal dismay, would have ever imagined that an unopened letter could do what they did,'' he said. Would Ms. Nguyen's illness reveal yet another missed link in the chain of reasoning and evidence?

Dr. Ostroff was hardly a novice. In 15 years at the disease control agency, he was one of the agency's most trusted detectives, helping to respond to the outbreak of hantavirus among American Indians in the Southwest, West Nile virus in New York, Ebola in Reston, Va.

Now, on the morning of Oct. 30, preparing to help the city respond to this new threat, Dr. Ostroff anxiously arrived at City Hall so early that the night-duty police officer had to let him in. He was escorted to the mayor's anteroom, where he fell asleep on a couch. The mayor woke him up when he arrived for the 8 a.m. meeting about the Nguyen case.

''We are about to see a lot of sick people in New York,'' Dr. Ostroff kept thinking.

New York -- hardest hit by the Sept. 11 attacks -- still seemed deeply vulnerable, both to attack and to panic. The city's health department, only a few blocks from the still smoldering ashes of the World Trade Center, had been intently preparing for a bioterror attack that might send tens of thousands of acutely ill people to city hospitals all at once.

But as the inquiry intensified, the mysteries only deepened. Investigators could not find even a single spore of anthrax near Ms. Nguyen's home in the Bronx, or at the Manhattan Eye, Ear and Throat Hospital, where she worked. No else got sick, which eased anxieties at the health department but also added to the sense of incomprehensibility.

Ms. Nguyen, who died Oct. 31, was not the harbinger of a feared new mass attack -- but neither, it seemed, would the evidence about her infection provide the break in the investigation that Dr. Ostroff and others had hoped for. One F.B.I. theory had been that Ms. Nguyen might have crossed paths with the bioterrorist. Now, all they knew for sure was that she had somehow been infected with anthrax in a place health officials could not find and in a way that had left no trace.

Connecticut
Revising the Textbook, One More Time

Dr. Joxel Garcia, Connecticut's health commissioner, had been working almost nonstop for six days to unravel the death of Ottilie Lundgren, the 94-year-old widow from Oxford, Conn., who on Nov. 21 became the nation's fifth fatality -- and his state's first -- attributed to inhalation anthrax.

Investigators had been sent to her favorite neighborhood dinner spot, her hairdresser, her bank, her church, her library and, of course, her local post office and her home. Nothing so far had turned up.

But on the evening of Nov. 27, Dr. Garcia's staff had made a discovery that at first seemed like wild coincidence: An 85-year-old man who had lived in the town of Seymour, about a mile and a half from Mrs. Lundgren, had also recently died. And he had lived right next door to a family that Postal Service officials said had received a letter postmarked in Hamilton, N.J., at nearly the same instant that the toxic letter to Senator Daschle had been processed.

Perhaps, this new evidence suggested, a letter that merely crossed paths with an anthrax-laced envelope could pick up enough spores to kill. If so, maybe that was how Mrs. Lundgren caught the disease, and her elderly neighbor, Oscar B. Haines -- and Ms. Nguyen in New York as well.

The implications were disturbing. Hundreds of thousands of letters -- perhaps millions -- had passed through the postal system since the anthrax mailings, and might now be contaminated with small amounts of anthrax that, if the theory held, might be lethal under certain conditions.

Dr. Garcia immediately called Gov. John Rowland, then the F.B.I., then the state's chief medical examiner. The first question on everyone's mind was as ghoulish as it was simple: Where was Mr. Haines's body now?

An F.B.I. agent and three state epidemiologists were dispatched to wake up the Farkas family, which had received the Hamilton letter, and swab their mailbox for spores. H. Wayne Carver II, the chief state medical examiner, tracked down the funeral home director who had Mr. Haines' body and ordered it sent over immediately to the state laboratory for examination. 

Two months after the first anthrax victims like Ms. Huden had suffered in anonymity, the nation's sprawling investigation had come to this: a desperate search in the night for the body of a man who might or might not have had the disease, and who in any case could no longer be helped, but who might still bear silent witness for the prosecution.

The autopsy, begun at 2:47 a.m., revealed that Mr. Haines did not have anthrax. His heart had simply failed. Dr. Carver called Dr. Garcia at about 4 a.m. with the news.

But when the investigators arrived at the Farkas's house on Great Hill Road in Seymour, they found to their astonishment that the letter postmarked in Hamilton on Oct. 9 had, for other reasons, been saved.

By Nov. 30, the investigators had the results -- the letter was positive for spores, and the news quickly spread out across the United States, once again changing the state of science about anthrax.

Cross-contamination was definitely possible. An innocuous letter, passing through the labyrinth of the postal system at the wrong moment, could become dangerous, as the Brentwood postal worker had insisted to Dr. Richardson weeks ago. Though it had not killed Mr. Haines, cross-contamination still might explain Mrs. Lundgren's death.

Epidemiologists were still confused. How could anthrax that had merely settled on a safe envelope suddenly get back into the air so it could be inhaled, causing the more serious form of the disease? That spores could become airborne again in the whirring tumult of a mail-sorting machine now seemed perfectly reasonable, but on a kitchen table? The answer had been found when they went through Mrs. Lundgren's trash -- clue-hunting of the sort Dr. Snow himself would smile on.

Mrs. Lundgren, it turns out, was quite particular about her mail. Again and again, she tore her letters precisely in half before throwing them in the trash, an act that could easily send any dust or anthrax spores flying back into the air.

The epidemiologists still did not know if in fact a cross-contaminated anthrax letter had arrived in Mrs. Lundgren's mailbox, and for all that they had learned, they didn't know whether, in the end, tearing such a letter in half had actually made a difference. But by then the idiosyncrasies of a little old lady seemed to be all they had to go on.

''In science, we keep the door open for everything,'' Dr. Garcia said then, two months and counting into the nation's anthrax inquiry.