HIS 15TH-FLOOR OFFICE ON Wilshire Boulevard offers a panoramic view of Los Angeles. Fresh tulips, lilies and irises are placed daily in vases beside his desk. There's a silver bowl of such immaculate, ripened strawberries that it seems criminal to actually eat one.

Everything in the office symbolizes Hollywood-style power and luxury -- the blood-red and ebony walls and matching carpet, the leather chairs, the Oscar on the desk. Then, of course, there are the personally inscribed photographs on the wall, of movie stars like Harrison Ford, Michael Douglas and Tommy Lee Jones, taken by the producer himself.

"I'm still star-struck," said Arnold Kopelson, the 60-year-old producer of "Outbreak," the new, and instantly popular, thriller about a killer virus. He smiled. "Coming from Brooklyn, where my parents used to deposit me in a movie theater every Saturday at 12 noon, I grew up with movies. When I'm with a well-known star, I get highly charged. I think this is why I make movies."

After years of hustling on the edges of the movie business, Mr. Kopelson leaped to prominence when he won the 1986 Oscar for producing Oliver Stone's "Platoon." Last year he received new acclaim when he made "The Fugitive," a blockbuster action film starring Mr. Ford. Now, in "Outbreak," Mr. Kopelson has another success.

Despite somewhat unfriendly reviews, the movie, starring Dustin Hoffman, Rene Russo and Morgan Freeman, climbed immediately to No. 1 at the box office when it opened last weekend. The fortuitous timing of the opening -- when there are few other studio movies around for anyone over the age of 16 -- helped make a hit of "Outbreak," a fictional drama about Motaba, a lethal monkey virus from Africa that threatens the United States.

If the plot sounds familiar, that is because Richard Preston's nonfiction book "The Hot Zone," about Ebola, a lethal monkey virus from Africa that threatened the nation, has been a best seller for five months. Mr. Kopelson first read about the virus in an article by Mr. Preston in The New Yorker in October 1992. The article became the basis for the book. "I was reading this New Yorker piece," Mr. Kopelson said, "and I thought, 'Wow! This is something.' I wanted to buy it."

Bidding for the movie rights began almost instantly. Mr. Preston said he received at least 30 calls from producers and others in the industry. Through his literary agent in New York, the writer hired Robert Bookman, an agent at Creative Artists Agency.

The bidding war reached its finale the weekend of Jan. 15, 1993. The most serious bidders telephoned Mr. Preston at his home in Princeton, N.J. The first call came shortly before 9 P.M. from Bruce Berman, head of production at Warner Brothers, who termed the article "sensational." Mr. Kopelson, working with Warner Brothers, followed with his own call.

At this point the recollections of Mr. Preston and Mr. Kopelson diverge. Mr. Preston said Mr. Kopelson had talked about how expensive the film would be and implicitly threatened to make a film about a virus anyway. Mr. Kopelson said he had made no threats but simply stated his intentions.

Finally, Mr. Preston said, he received a call from Lynda Obst, representing 20th Century Fox, who identified herself as a one-time journalist. She (and Fox) offered a $100,000 option, against $450,000 to be paid if the movie was actually made. Mr. Preston took Ms. Obst's offer over similar offers from Mr. Kopelson and others.

"The money was essentially the same," Mr. Preston said. "I went with Lynda because of her journalistic background."

"Crisis in the Hot Zone," Ms. Obst's $55 million film, was to star Robert Redford and Jodie Foster and be directed by Ridley Scott. But that project was stalled, mostly because of squabbling over the script.

Meanwhile, Mr. Kopelson would not give up. "For years I had wanted to do a film about a virus out of control," Mr. Kopelson said. "I had seen 'Andromeda Strain' and 'Panic in the Streets.' But there hadn't been one in a long time."

And so, irony of ironies, Mr. Kopelson, the man who had been attracted to a science-laden, factual article in The New Yorker, says he told Mr. Preston that Warners Brothers regarded the real-life story as too scientific and not grist for a dramatic film. In an interview, Mr. Preston denied having had this conversation with the producer and referred to Mr. Kopelson's negotiating style throughout as "hardball."

"Maybe he wasn't used to the truth and straightforwardness," Mr. Kopelson said. "That's not hardball. It's being honest."

SO MR. KOPELSON proceeded with "Outbreak," his $60 million virus movie. Unable to buy the rights to Mr. Preston's article, he and Warner Brothers hired Laurence Dworet, a doctor, and Robert Roy Pool to write an original script that covered similar material. He hoped for Harrison Ford in the lead, but when Mr. Ford turned down "Outbreak," he turned to Mr. Hoffman. Then he pushed his film into production, with Wolfgang Petersen as director, even when it looked as if the Redford project would proceed.

Just before "Crisis in the Hot Zone" was to begin filming last August, Ms. Foster quit the project; eventually, Mr. Redford did, too. That left Mr. Kopelson's movie the only virus film in town.

Mr. Hoffman was cast as an Army doctor trying to stop the virus before it spreads. Ms. Russo played his ex-wife, a doctor at the Centers for Disease Control and Prevention. Morgan Freeman was cast as Mr. Hoffman's supervisor, and Donald Sutherland was given the role of the Strangelovian general intent on using the Motaba virus for biological warfare.

But triumph was fleeting. Mr. Hoffman is notorious for seeking script revisions. At one point, he called Peter Jahrling, a senior research scientist at the United States Army's Medical Research Institute of Infectious Diseases. Mr. Jahrling, the researcher who first identified the Ebola-Reston virus, gave scientific advice to the film makers early during production of "Outbreak."

As Mr. Jahrling recalled, "Dustin Hoffman said, 'This script isn't making any sense to me. Could you explain it?' And I said to him, 'Don't ask me. Ask the fool who wrote it.' " Five more writers, earning at least $100,000 a week, flowed onto the set as the film was in production. They turned Mr. Sutherland's character more sinister and gave him an appropriate comeuppance.

They also wrote in action sequences, which led to the matter of the aerial dogfights between Army helicopters. "The Deparment of Defense absolutely and categorically had nothing to do with the making of this movie after reading the script that was going to present the whole biological warfare situation in a negative light," Mr. Jahrling said. "Kopelson wanted to use Army airplanes. They couldn't get Department of Defense assistance."

"Outbreak" depicts a lone worker who, in less than 24 hours, can identify and synthesize enough antibodies to treat an entire town full of people. "If you can make antibodies that worked," Mr. Preston said, "you might be able to clone up a lot of them to save a town. But it would take six months to a year.

"Not only is the movie a scientific mess," he added, "it's not even scary. They've taken a frightening subject and turned it into a charming potboiler."

Turning scientific rigamarole into a potboiler is part of a producer's job, along with negotiating with cranky Department of Defense officials and finicky superstars. Mr. Kopelson speaks carefully about the strains of making "Outbreak." "I am very pragmatic," he said. "The movie is the most important thing. It cannot come down to personalities. It has to do with what is best for the movie. I am representing the studio. My function is to protect the interests of the studio."

There was a time when Mr. Kopelson's only contact with studios was as a lawyer who specialized in motion picture financing. In the 1960's and 70's, he traveled to the third world, where he met independent distributors hungry for American movies. In the early 70's, working on his own, he bought the foreign rights, sight unseen, to a forgettable Columbia film called "The Last Rebel," which starred Joe Namath and Woody Strode.

"I was so happy to get a film, I didn't even look at it," he recalled. "When I saw the movie I said, 'This is terrible.' But then the checks starting coming in, and all of a sudden I was making more money on this deal than I ever made in a single year practicing law."

With his longtime legal assistant and future wife, Anne Feinberg (his first wife, Joy, with whom he has three grown children, died in 1975 of cancer), Mr. Kopelson established Inter-Ocean Film Sales in 1972. This company represented a combination of good and bad films abroad, including the works of John Cassavetes. (Anne Kopelson, a savvy and forthright co-chairwoman of her husband's company, now oversees his business affairs.)

By the late 1970's, Mr. Kopelson had forged a deal with General Cinema Corporation to produce films. "I didn't know what a good script was," he said. "I didn't know how to put together a cast and crew." But he found a small gold mine in "Porky," a film he helped create, which was targeted to the adolescent market. "Porky" grossed $105 million domestically in 1982.

A GAMBLER, MR. KOPELSON, along with his wife, took a major risk in the early 1980's and moved into banking and gold-mining ventures, which ultimately failed. They lost millions. Shaken and facing financial problems, the couple sat down and decided to focus entirely on gaining a foothold in the movie business. They read the script for Mr. Stone's "Platoon," the scorching Vietnam War drama that had been turned down by most studios, and took it to Hemdale, a small British studio. Money was raised through bank loans and foreign sales.

"With 'Platoon' I realized the enormous impact that a movie can make," he said. "It was then that I took producing very seriously."

Mr. Kopelson followed the success of "Platoon" with the 1989 Holocaust drama "Triumph of the Spirit," starring Willem Dafoe. The film performed weakly at the box office. But then in rapid order he made "Out for Justice," with Steven Seagal, "Falling Down," with Michael Douglas, and "The Fugitive," the film that placed him in the top tier of producers. Last year he was named producer of the year by the nation's theater owners. He has a lucrative deal at Warner Brothers, an office staff of 15 and a roster of forthcoming films with stars like Brad Pitt and Arnold Schwarzenegger.

Not only does Mr. Kopelson's lush office bespeak his success; so does his home in Beverly Hills, an enclave replete with a state-of-the-art screening room in which the producer, an insomniac, often watches movies alone in the middle of the night. On Sundays, the man who thinks of himself as an old-time movie mogul holds catered screenings there. "Sometimes I can't quite believe that I'm doing this," he said. "It's a dream."

Most of the stars he has cast speak of him warmly. "What makes Arnold such a good producer is his hard work, dedication, focus and more hard work," said Mr. Ford. "He showed me the script of 'The Fugitive,' and it was only 50 percent there. But he got me involved and stayed involved. He never overwhelmed the so-called artists like myself and the director and the writers. He understood our ambitions. And he never held us back. Arnold's a mensch and more."

Morgan Freeman, who will be seen both in "Outbreak" and in a new Kopelson thriller, "Seven," with Brad Pitt, added with a laugh: "Arnold is really like a big, warm mother. He has a real nurturing sense with actors. He just gives you this real sense of security."

Concern that smallpox virus may be used as a biological weapon of mass destruction has prompted calls for production of additional vaccine and new research into variola virus diagnostics and clinical interventions. Only 15.4 million doses of smallpox vaccine, produced approximately 20 years ago, exist in the United States (1). While virtually all lots remain potent, additional vaccine would clearly be needed in a national emergency involving smallpox virus. Global eradication of natural smallpox disease was declared in 1980; with eradication, most research activities involving the virus ended. Although the complete genomic sequence of selected isolates of variola virus is known (2), the diagnosis and treatment of smallpox infection have not changed in the past two decades. Recognizing the need for advancement in these areas before variola virus stocks are destroyed, the World Health Organization (WHO) passed a resolution (WHA 52.10) in 1999 extending the date of destruction of all remaining variola virus stocks until the end of 2002. The midpoint of this period is an appropriate time to review progress made in vaccine production and variola virus research and to outline the next steps.

Vaccine Production

On September 20, 2000, the Centers for Disease Control and Prevention (CDC) entered into an agreement with OraVax (Cambridge, MA) to produce a new smallpox vaccine. Like the vaccine used to eradicate smallpox, the new vaccine will contain live vaccinia virus; however, it will be produced in cell cultures by modern vaccine production techniques. OraVax will coordinate full clinical testing of the vaccine and submit a licensing application to the U.S. Food and Drug Administration (FDA) for the prevention of smallpox in adults and children.Forty million doses of the new vaccine will be produced initially, with anticipated delivery of the first full-scale production lots in 2004. The agreement calls for sustained annual production through 2020 to replace outdated vaccine and allows for increased production should an emergency arise. The vaccine will be administered with bifurcated needles (also produced by OraVax), which create a localized vaccine “pock” and confer protective immunity. The vaccine will be held in reserve as part of the national stockpile and be released only in the event of a confirmed case of smallpox or when vaccination against vaccinia virus is warranted. The agreement allows OraVax to produce additional vaccine for other markets, including international buyers.

Variola Virus Research

A research plan, implemented at CDC by scientists from both the Department of Defense and CDC and including extensive collaborations with scientists from the National Institutes of Health and other organizations, is being undertaken with WHO concurrence. All work with live variola virus is done under biosafety level 4 containment conditions at CDC. Smallpox virus is officially retained at only two facilities in the world: at CDC in the United States and the State Research Center of Virology and Biotechnology in Novosibirsk, Russia. Research teams from both institutions are coordinating activities to avoid duplication and gain the maximum amount of information possible before final destruction of the virus.

Strain Evaluation

Of 461 isolates in the smallpox virus collection at CDC, 49 were selected for further characterization. These isolates, which included both variola major and variola minor, were selected to represent the greatest diversity in date of collection and geographic region. Of the 49 isolates tested for viability, 45 were successfully recovered, and seed stocks were prepared for subsequent studies. This group of 45 represented isolates from as early as 1939 and as late as the 1970s; all major geographic regions were represented. Study of these isolates is based on three research themes: application of modern serologic and genomic methods in the diagnosis of variola virus disease; determination of candidate antiviral drug activity against this virus; and investigation of the pathogenesis of smallpox infection, especially through the development of a nonhuman primate model to replicate human smallpox infection. The research team carefully outlined all experimental work to be undertaken with variola virus, incorporating suggestions from a peer group of highly qualified external experts from academia and industry; the first set of experiments was conducted from January to July 2000 in the CDC maximum containment laboratory.

Serologic Assays

Because enzyme immunoassay technology was still in its infancy when smallpox was eradicated, during the first series of experiments, polyclonal and monoclonal antibodies had to be produced for developing enzymelinked immunosorbent assays to measure variola virus-specific immunoglobulin (Ig) M, IgG, and antigen. These reagents are now being evaluated by prototype assays with inactivated viral antigens. This work will continue for the foreseeable future.

Nucleic Acid-Based Diagnostics

Viral DNA was extracted from all 45 successfully recovered isolates, was purified and inactivated, and is now being examined by restriction fragment-length polymorphism developed by an extended polymerase chain reaction assay that amplifies viral genome into 20 overlapping products of approximately 10 kilobases each. These products cover virtually the entire length of the viral genome and include sequences in essential genes and genes likely needed for pathogenesis. Preliminary results indicate that the data thus generated offer a good low-resolution overview of genetic diversity of variola viruses and are being used to differentiate strains, infer phylogeny, and identify as many as 10 additional variola isolates for complete genome sequencing. Two isolates, Somalia 77 and Congo 70, were specifically suggested by WHO for sequencing, and this work has begun. A dedicated sequence and bioinformatics facility being developed at CDC will be used to undertake this effort and to begin constructing a genomic signature database, not only for smallpox but also, over time, for other pathogens with bioterrorism potential.

Antiviral Drugs

Two hundred seventy-four antiviral drug compounds were screened for activity and therapeutic indices against variola, monkeypox, cowpox, camelpox, and vaccinia viruses by two cell culture assays. Many of these compounds were provided for testing under collaborative arrangements facilitated by an orthopox antiviral research initiative of the National Institute of Allergy and Infectious Diseases. Previous studies identified a nucleoside phosphonate DNA polymerase inhibitor, cidofovir (Vistide), as being active against poxviruses, including variola. In the current trial, cidofovir and its prodrug (cyclic HPMPC) were evaluated against 31 strains of variola, which were selected to cover a wide geographic area and time span. No substantial differences in inhibition among strains were observed, which suggests that cidofovir-resistant strains are unlikely. The in vitro inhibition was further characterized in multiple cell lines to meet FDA requirements. However, another class of antiviral drugs, the S-adenosylhomocysteine hydrolase inhibitors, showed considerable variation in the 50% inhibitory dose between variola isolates; this effect should be investigated further.

Two approaches to the development of an oral prodrug of cidofovir yielded compounds with improved antiviral activity. In addition, the current series of experiments identified 27 other compounds, including completely new classes of drugs, that appear to be active against variola and other orthopoxviruses. In fact, 10 compounds had therapeutic indices greater than 200, while cidofovir had indices greater than 10; 3 compounds had therapeutic indices greater than 1,500. When work resumes in early 2001 with live variola virus, we will continue to evaluate these and additional compounds for activity, including analogs designed for oral administration. The most promising compounds emerging from this in vitro testing will be evaluated in animal models, e.g., cowpox and vaccinia in mice and eventually monkeypox virus challenge in nonhuman primates. All promising compounds will be tested against a battery of surrogate orthopox viruses to guide evaluation of new antiviral compounds after variola virus is no longer available.

Animal Models

A major goal of the current research is to define an animal model that faithfully replicates human smallpox. Such a model would be extremely valuable in evaluating candidate antiviral drugs and novel diagnostic assays and in defining the pathogenesis of smallpox. Consequently, two groups of four cynomolgus macaques were exposed to two variola virus strains at a high dose (>108 PFU) by the aerosol route. Clear evidence of infection was found; the animals had transient fevers, perturbations in cytokine titers in serum, and mild exanthemous lesions. A few of the monkeys showed signs of bronchopneumonia, but none died or had disease similar to the classic smallpox seen in humans. Another series of experiments will be undertaken with different variola isolates to confirm these preliminary observations and generate additional clinical material to validate the diagnostic assays under development.

The results of the research now under way, coupled with the promise of renewed production of smallpox vaccine, will better prepare the United States—and indeed the entire world— for the possibility that smallpox virus might be used as a terrorist weapon of mass destruction.

James W. LeDuc* and Peter B. Jahrling†

*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; †United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA

References

1. LeDuc JW, Becher J. Current status of smallpox vaccine. Emerg Infect Dis 1999;5:593-4.

2. Shchelkunov SN, Massung RF, Esposito JJ. Comparison of the genome DNA sequences of Bangladesh-1975 and India-1967 variola viruses.

Virus Res 1995;36:107-18.

In late September, in the days before a series of anthrax-tainted letters made bioterrorism a reality in the United States, President Bush decided that the federal government should acquire enough vaccine to protect every American against an even more menacing biological threat: smallpox.

Although smallpox was eradicated as a disease in the 1970's, American intelligence had suspected for years that Iraq and North Korea, and possibly other rogue nations, had maintained clandestine stocks of the deadly smallpox virus.

But officials say it was the attacks on the World Trade Center and the Pentagon, and not any new information, that prompted the president's decision to greatly expand the nation's smallpox vaccine stockpile.

The decision, which was not publicly announced, gained urgency when letters containing potentially lethal anthrax powder began arriving at news organizations and on Capitol Hill. The anthrax scares produced widespread fears that the nation would run short of the antibiotic Cipro. So senior administration officials quietly sped up their timetable for acquiring the smallpox vaccine.

Last Wednesday, [Tommy George Thompson (born 1941)], the secretary of the Department of Health and Human Services, announced the plan, which calls for stockpiling the vaccine so that it can be used in the event of an outbreak of smallpox, a highly contagious disease for which there is no treatment, and that kills one-third of all people infected with it.

''I think the American people will feel much more comfortable knowing they have their name on a vaccine shot in our inventory,'' Mr. Thompson said in an interview. ''It's the security of knowing you have enough for every American.''

The decision to buy 300 million doses will vastly accelerate an existing vaccine program that, in the view of many scientists and federal officials, was hampered by bureaucratic inefficiency and was moving much too slowly. It also illustrates just how concerned officials have become about the nation's preparedness for a bioterrorism attack.

Despite [Tommy George Thompson (born 1941)]'s public pronouncements on Sept. 30 that the government ''can handle any contingency right now,'' interviews with nearly a dozen administration officials, scientists and bioterrorism experts make clear that in the aftermath of the Sept. 11 attacks, both the health secretary and the White House privately were acutely aware of the nation's vulnerabilities.

Even so, it was not until Oct. 4 -- just hours before Mr. Thompson announced to the nation that a Florida man had become sick with pulmonary anthrax -- that he secured Mr. Bush's commitment to pay for his entire $1.6 billion bioterrorism preparedness package.

''It was the double whammy of the World Trade Center and the anthrax attack that made everybody realize that these are real problems that need to be dealt with,'' said [Dr. Peter B. Jahrling (born 1946)], an Army scientist who is one of the nation's leading smallpox researchers. ''In all my years of government service, I have never seen anything move this fast.''

Mankind's triumph over smallpox is considered public health's greatest accomplishment. After the World Health Organization officially declared in 1980 that the disease had been eradicated, countries were supposed to destroy their stocks of the smallpox virus and transfer any samples of it two repositories, one in Russia and the other in the United States, at the Centers for Disease Control and Prevention in Atlanta.

By the early 1990's, the United States had about 15 million doses of aging smallpox vaccine that had been made by Wyeth Laboratories. It was too little to protect civilians and military forces, but few civilian scientists believed that the disease would ever re-emerge.

The military, however, thought otherwise. In 1989, Vladimir Pasechnik, a top Soviet biologist, defected to Britain. In briefings later shared with American military intelligence analysts, he described the Soviet Union's empire of thousands of scientists and dozens of secret cities and facilities devoted to turning germs and viruses, including smallpox, into weapons. And he said Moscow was trying to modify smallpox into an even more efficient killer.

These accusations, bolstered by the 1992 defection to the United States of Ken Alibek, the No. 2 scientist in the secret Soviet program, led American scientists at the Army's biological defense laboratory at Fort Detrick, Md., to press for the development of a more modern vaccine.

In 1997, the Pentagon awarded a contract to [DynPort Vaccine Company, LLC], an American-British company, to do just that.

The next year, a special panel of experts urged President Bill Clinton to start a vaccine program for civilians. Because vaccination was stopped in 1972, and immunization against smallpox lasts only 15 to 20 years, Americans are especially vulnerable, experts say.

At the Department of Health and Human Services, [Dr. Margaret Ann "Peggy" Hamburg (born 1955)] oversaw the smallpox effort. Administration officials worried that they would not get support for the plan in Congress. ''A lot of people thought this was a crazy idea, to make new vaccine when the disease didn't exist,'' Dr. Hamburg said.

At the White House, Richard A. Clarke, President Clinton's counterterrorism coordinator, wanted the Pentagon and the health agency to join forces. But the Pentagon refused to share the seed strain for its program with the civilian program.

In an interview last summer, a spokesman for the office charged with making the vaccine, the Joint Vaccine Acquisition Program, said there were legal impediments to cooperating with a civilian contractor. Among other factors, he said, product liability was a concern.

''These were two diametrically opposite bureaucracies that had no history of dealing with one another,'' said Mr. Clarke, who now leads Mr. Bush's office to protect the nation against Internet threats.

The result was two separate smallpox vaccination programs. The military contract with [DynPort Vaccine Company, LLC] called for 300,000 doses at a cost of $22 million, or initially about $70 a dose, to be delivered around 2005 or 2006. The civilian contract, which was awarded to OraVax, a Massachusetts-based company that has since been acquired by Acambis, a British concern, called for 40 million doses to be delivered by 2005, at a cost of $343 million, at about the same time as the military vaccine.

One senior administration official called the situation ''an utter mess.''

Even before the Sept. 11 terrorist attacks, the Bush administration was determined to straighten the problem out. In June, a team of bioterrorism experts, led by the Johns Hopkins University Center for Civilian Biodefense Studies, conducted an exercise code-named Dark Winter that simulated an outbreak of smallpox in the United States. As the imaginary epidemic spread, growing grimmer and grimmer, the government quickly ran out of vaccine.

''After Dark Winter, there was a whole spate of briefings, so that a whole lot of people suddenly began to realize just how serious an epidemic of this sort could be,'' said Dr. Donald A. Henderson, who directs the center at Johns Hopkins and led the global effort to eradicate smallpox.

On Sept. 16, [Tommy George Thompson (born 1941)] brought Dr. Henderson into his inner circle of advisers. The men met for the first time that day.

''This was a man deeply troubled and very worried,'' Dr. Henderson recalled. Mr. Thompson acknowledged as much. ''Where will they hit us if they're going to hit us again?'' he remembered thinking.

By this time, Mr. Thompson was already pressing the White House to improve the nation's bioterrorism defenses. He found allies there among several officials who were steeped in biodefense.

[Irving Lewis "Scooter" Libby (born 1950)], a top Pentagon lawyer in the first Bush administration who is now Vice President Dick Cheney's chief of staff and national security adviser, arranged for his boss to see a video of the Dark Winter exercise on Sept. 20. Lisa Gordon-Hagerty, who directs a National Security Council program to defend against weapons of mass destruction, was also supportive.

Officials said the vice president was so alarmed by the exercise that he raised the smallpox vaccine issue at a National Security Council meeting later that day. ''The vice president was pushing it, and the president was going along with it,'' a senior administration official said.

Within [Tommy George Thompson (born 1941)]'s circle of advisers, however, there was serious debate about whether 300 million doses were actually needed. Dr. Henderson's group at Johns Hopkins had estimated that only 100 million to 135 million doses would be needed to curtail an outbreak, and people familiar with the discussion say Dr. Henderson argued that money might be better spent on improving the public health infrastructure.

Others argued that the government needed a dose for every American, if only to avert panic. Among them was Michael T. Osterholm, a public health expert who is also advising Mr. Thompson. He declined to talk about the deliberations, but said, ''There is a certain psychological benefit to knowing that, in this country, there is a dose of vaccine for everybody if we need it.''

The secretary agreed and, sometime after Sept. 20, secured verbal approval from the president for the program. On Oct. 3, Mr. Thompson announced that his agency had arranged for Acambis to speed up its work and deliver the doses by the end of next summer.

The next day, anthrax hit America.

As the news was breaking in Florida that a man there was sick with pulmonary anthrax, a disease not seen in this country for a quarter-century, [Tommy George Thompson (born 1941)] was at the White House, briefing the president and vice president on his bioterrorism plans.

Officials say that briefing was a pivotal moment. The president committed the $1.6 billion for the broad antibioterrorism package. When it was over, Mr. Thompson briefed the press about the anthrax infection. Over the next several days, it became clear that the case was a deliberate attempt at anthrax poisoning.

''When the anthrax hit, it was like, whoof!'' Dr. Henderson said. ''Sort of like a blow in the stomach.'' The next Monday, Oct. 8, Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, received an order from Mr. Thompson's chief deputy, Claude Allen. His mission, Dr. Fauci said, was ''to determine the scientific and technical feasibility of rapidly expanding the production of smallpox vaccine.''

That Friday, a collection of the nation's top scientists and public health officials gathered in Dr. Fauci's office on the campus of the National Institutes of Health in Bethesda, Md. They included representatives from the Food and Drug Administration, the disease control centers and Dr. Fauci's institute, as well as [Dr. Peter B. Jahrling (born 1946)], the Army scientist.

''It was a high state of adrenaline,'' Dr. Fauci recalled. He remembered telling the assembled scientists: ''We have been given a task. We are going to get it done, and we are going to get it done on time. Failure is not an option.'' One concern, he and others said, was that the administration was taking a risk by relying on just one company, Acambis, to make the smallpox vaccine. So by this time, officials from Mr. Thompson's office were already meeting with other vaccine manufacturers, including Merck and Baxter International, which has a 20 percent stake in Acambis, to determine whether they would help in the effort.

''I think you want to diversify the risk,'' [Dr. Peter B. Jahrling (born 1946)] said. ''In a world where planes hit trade centers and the whole thing comes crashing down, I think you probably want to make this stuff in more than one place.'' And while Dr. Fauci's institute was already running tests to see if the existing stockpile of 15 million doses could be safely diluted to create 75 million, everyone at the meeting agreed that was not good enough. By the time it was over, they had agreed to get a draft proposal for buying 300 million doses to [Tommy George Thompson (born 1941)] by Oct. 17.

''We were on a very fast track,'' Dr. Fauci said.

So fast, in fact, that Mr. Thompson did not even wait for the draft to announce his plans. He did not need to, he said. The decision had already been made.

In 1980, D. A. Henderson did what no one else in history has ever done. He wiped a disease, smallpox, off the face of the earth. Now, smallpox is back -- not as a naturally occurring killer but as a potential bioterrorist weapon. And D. A. Henderson is back, too.

At 73, the man who led the global effort to make the world safe from one of its deadliest scourges has re-emerged as the director of a new government program to make the nation safe from bioterrorism. His challenge is to prepare the United States for a germ attack at a time when the country is already deep into a war against terrorism.

''D. A. has, in essence, been the man for all seasons in science,'' said Dr. Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. ''I think he is obviously in his final season, but it may be the most important season he ever had.''

It is a season that is quickly becoming fraught with complications for Dr. Henderson, who has spent the past decade waging a determined, passionate -- and, critics say, misguided -- campaign to destroy the last remaining vials of the smallpox virus, in part to prevent it from being misused. This week, the Bush administration decided to retain the virus so scientists can use it to develop a range of new vaccines and treatments for the disease.

The decision means that the smallpox germ will very likely outlive Dr. Henderson, who is now in the uncomfortable position of having to defend the White House stance.

''There is a lot of concern about what D. A. in his new, highly exalted position, is going to say,'' said Dr. Peter Jahrling, a virologist at the Army's bioterrorism preparedness laboratory in Fort Detrick, Md., who has been Dr. Henderson's chief opponent in the destruction controversy. ''Is he actually going to change his tune?''

In an interview on Friday, just as the administration was announcing its decision, Dr. Henderson answered that question with diplomacy, if not enthusiasm. ''I'm a member of the administration at this point in time,'' he said simply, ''and so I necessarily have to be in accord with the administration's position.''

Formerly the director of the Johns Hopkins University Center for Civilian Biodefense Studies, a research institution that he founded in 1997, Dr. Henderson has been warning about bioterrorism since the mid-1990's. On Nov. 1, Tommy G. Thompson, the secretary of health and human services, named Dr. Henderson to head the new Office of Public Health Preparedness. The appointment came as the administration was facing criticism for lack of coordination in its handling of the recent anthrax attacks, which killed four Americans and sickened more than a dozen.

''He really didn't want to do it,'' Tara O'Toole, who now directs the biodefense studies center, said. ''But he didn't see any honorable way to say no.''

A burly man with a full head of white hair, silver-rimmed glasses and a deep, gravelly voice, Donald Ainslie Henderson has a physical presence as towering as his reputation.

On a recent afternoon, he was seen in his government office, a spartan affair with a cardboard nameplate propped atop a fax machine. Standing against the sky-blue window treatments, suspenders pressed close against a stark white shirt, he exuded confidence, looking like the president in a Hollywood movie.

People in public health sometimes refer to Dr. Henderson as ''the old man,'' borrowing the term soldiers use for generals they respect. He is uniformly described as a gracious mentor, albeit a demanding one.

''He does not suffer fools gladly,'' said Dr. Margaret A. Hamburg, a bioterrorism expert at the Nuclear Threat Initiative, a nonprofit foundation in Washington. ''And he is accustomed to the power of command.''

Those who know Dr. Henderson well wonder how his new mission will go. He does not like bureaucracies, yet he is now in the belly of a bureaucratic beast.

The labyrinthine Health and Human Services Department is a collection of agencies. President Bush has yet to fill the top posts at two, the National Institutes of Health and the Food and Drug Administration. And an important position at the parent agency, the job of assistant secretary for health, is also vacant. It will be up to Dr. Henderson to draw these agencies together and form alliances with law enforcement and intelligence authorities.

''He believes that rules are for mere mortals to follow,'' said Jonathan B. Tucker, the author of ''Scourge: The Once and Future Threat of Smallpox'' (Atlantic Monthly Press, 2001).

''Sometimes I think he can rub people the wrong way because he is such a formidable personality and is so confident. Some people perceive that as arrogance,'' he said, adding that that was not his own experience of Dr. Henderson. ''I think that's the risk of his approach. But of course, he has great credibility, given his history.''

That credibility goes a long way on Capitol Hill. Last week, when Dr. Henderson appeared before a House committee, he was introduced by Representative Billy Tauzin, Republican of Louisiana, as ''a real American hero.'' The lawmakers then gave him a standing ovation; he shook his head and tried to wave off the applause. ''In truth,'' he said later, ''it's a little embarrassing.''

An ancient, contagious and particularly hideous disease, smallpox kills a third of those infected with it, and Dr. Henderson is one of the few doctors in this country today to have actually seen a case.

The World Health Organization's smallpox eradication program, which Dr. Henderson ran from 1966 to 1977, was, he said, the effort of countless public health workers who toiled under grueling conditions, often living in villages without electricity and running water, in nations torn apart by war. They operated under the principle of ''ring vaccination,'' containing outbreaks by vaccinating every patient infected, and everyone around those patients, moving outward in concentric circles until the virus stopped spreading.

Dr. Henderson's admirers say he should win a Nobel Prize, yet he was recently passed over for another prestigious award, the Lasker Foundation Award for public service. The prize went to Dr. William Foege, a former director of the Centers for Disease Control and Prevention who participated in the smallpox eradication effort and devised the ring vaccination strategy.

Despite the lack of official recognition, experts on smallpox say there is little doubt that the eradication effort, conducted in partnership with the former Soviet Union at the height of the cold war, succeeded in large part because of Dr. Henderson's cunning and derring-do.

When the Ethiopian health minister refused to cooperate with him, Dr. Henderson sneaked into the country and befriended the personal physician of the emperor, Haile Selassie. When Dr. Henderson believed the Russians were providing him with inferior smallpox vaccine, he went to Moscow -- against direct orders from his superiors, who feared a diplomatic disaster -- and demanded a better one.

''He created a lot of very loyal employees who were willing to go the extra mile,'' Dr. Tucker said. ''If vaccine had to be sent out on Christmas Day, people would come in on Christmas Day to get the job done.''

The world's last case of smallpox occurred in 1978, in England, when the virus escaped in a laboratory and infected a medical photographer. Two years later, it was declared eradicated worldwide. Nations that held samples of the virus were encouraged to either destroy them or transfer them to one of two official repositories that still exist, one in Russia and the other at the Centers for Disease Control, in Atlanta.

Dr. Henderson became dean of the Johns Hopkins School of Public Health, a post he held until the first Bush administration, when he served as science adviser to the White House.

When Bill Clinton was elected president, Dr. Henderson took a job in the health and human services agency, working as science adviser to Donna E. Shalala, Mr. Thompson's predecessor. But he left in 1995, saying he was not being consulted on issues of importance to him.

That year, Dr. Henderson said, he learned of the work of Ken Alibek, who ran the Soviet Union's biological weapons program and claimed to have developed smallpox as a weapon. But while Dr. Henderson became more concerned about bioterrorism -- enough so that he founded the Johns Hopkins center -- he nonetheless advocated destroying the official smallpox stocks, for several reasons, he and those close to him say.

First, the eradication program was an international effort, and other nations wanted the virus destroyed.

''We had countries around the world saying, 'Why are Big Brother United States and Big Brother Russia keeping the virus?'' Dr. Henderson said. Second, he said, there was a danger that the virus could escape, as it did in England. Third, by destroying its stocks, the United States could make possession of it a crime.

But national security experts and military scientists countered with the argument that has prevailed: only by keeping the virus would the United States be able to develop better treatments for a smallpox attack. Dr. Jahrling, of Fort Detrick, said recently that Dr. Henderson viewed destruction as ''the crown jewel in his career'' -- a contention that Dr. Henderson dismissed in Friday's interview as ''mythology.''

Dr. Henderson may not stay long in his new job; he said he was committed to remaining with the government only as long as it took to create a bioterrorism preparedness program that others might carry out. Asked how long that might be, he replied by saying that he had promised the World Health Organization he would stay in Geneva for 18 months. He stayed 11 years.

More than anything, Dr. Henderson said, he would like to figure out a way to persuade the countries of the world to come together to condemn the use of germs as weapons. Of smallpox, he said, ''We've got to put the genie back in the bottle.''

ATLANTA -- In an experiment unfolding under tight security, six rust and silver monkeys this past week grew listless, refused to eat, and broke out in blisters. Four have become sick, and two have died. The cause: smallpox.

On June 18, microbiologist Peter Jahrling and a team of spacesuited scientists passed through steel doors with key cards, and entered an air-locked laboratory -- the "Hot Suite" -- at the Centers for Disease Control and Prevention. Their mission: to infect animals with an extinct disease that is now the world's most feared bioterror pathogen.

Historically, smallpox killed millions of people and left millions more scarred or blind. But by 1980, the World Health Organization had eradicated it. Now, just two sanctioned repositories of frozen virus exist, the one here and one in Russia. But the Sept. 11 attacks on the World Trade Center and Pentagon, and the anthrax letters that followed, have raised fears of terrorists' procuring the virus and unleashing it.

The point of the experiment here is to create an animal model of human smallpox. Never before achieved, it is critical to creating 21st-century drugs and vaccines in case of an epidemic. Animal models are systems for testing treatments without endangering human volunteers. Currently, no drugs exist to treat smallpox. And the vaccine to immunize against it, while effective, causes side effects, including death in about three out of every million people vaccinated.

Doctors stopped giving smallpox shots in 1972, so most people under 30 aren't vaccinated. Even among the vaccinated, immunity has eroded with time, leaving most people vulnerable. Scientists hope the monkey model might help them develop both safer vaccines and an effective treatment.

Now government health officials have made smallpox drugs a priority of biodefense research, setting off a rancorous debate. Alfred Sommer, dean of the public health school at Johns Hopkins University in Baltimore, calls the animal work "an abhorrent experiment by government idiots." He warns that it could spark a bioweapons arms race with countries such as Iraq and North Korea. The way to fight smallpox isn't by injecting monkeys, he says, but by destroying the stockpiles of virus. Dr. Sommer says 18 of the nation's 29 public-health school deans signed his petition calling for destruction of the stockpiles. This past spring, the WHO and the Bush Administration agreed to preserve the virus until new drugs were developed.

D.A. Henderson, the leader of the WHO's successful smallpox campaign, also thinks the Jahrling project is misguided. He doubts doctors will ever find a drug to treat the disease once its lesions appear, and thinks the government should be spending its time and money finding a drug to treat reactions to the vaccine. Dr. Henderson is currently senior scientific adviser on public-health preparedness to Health and Human Services Secretary Tommy Thompson.

"We're very proud of the research agenda that's under way," says James LeDuc, the CDC's director of viral diseases and its point man on smallpox, defending Dr. Jahrling's work. "There's been a lot of hysteria." But now, he adds, "It's yielding positive results. We're happy to share the good news."

After the Sept. 11 attacks occurred, Dr. Jahrling, a senior research scientist at the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md., was impatient to follow up work he began a summer ago with an initial experiment on monkeys. For months the 56-year-old researcher waited his turn at the CDC's only smallpox lab. Finally, he got the green light and hoped to infect monkeys on June 13.

On June 3, an advance team thawed vials of virus from the CDC's freezer. Mixed into flasks containing a culture of monkey kidney cells, the virus grew more slowly than expected, delaying the test five days. "An experiment of this complexity is like a space launch," Dr. Jahrling says. "Everything must be perfect."

At 10 a.m. on June 18, members of the team were dressed in green surgical scrubs and zipped into biohazard suits with attached hoods, booties and gloves. They taped on outer gloves and boots for extra security. Onto this protective skin, they hooked coiled orange hoses of filtered air. The air inflated their suits, making them look like the Michelin man. Then, the bulky figures entered Biosafety Level 4 Laboratory, one of two top-level containment facilities for deadly viruses here at the CDC. Its twin lab houses hemorrhagic fever viruses, such as Ebola.

Dr. Jahrling has courted controversy by giving monkeys as many as one million times the dose that is infectious to humans, and by exposing them in a different way. People contracted smallpox by inhaling the virus. But macaques, the monkeys used in this experiment, don't get smallpox in nature. Previous aerosol exposures produced only a mild nonlethal rash.

To try to infect monkeys with lethal smallpox last year, Dr. Jahrling double-dosed them with aerosol and intravenous virus, using a super-virulent strain -- India I -- the strain of choice of former Soviet germ warriors. If anything, it worked too well.

"By day four, they checked out," says Dr. Jahrling. Death came so swiftly that the blisters barely budded, leading critics to charge that the monkeys died, not from smallpox, but from blood poisoning. So this time, Dr. Jahrling employed a less-hot virus called the Harper strain. Forgoing "that hellacious fog," he used only an IV infusion. His aim: to slow the disease down to something resembling the 10- to 14-day course of human smallpox.

To maintain virulence, he still set the dosage at between 100 million and one billion infectious units of the virus, an amount almost certain to be lethal. He grants that that exceeds the 30% human death rate that would be expected from an actual outbreak of the disease. But, an experiment designed to mimic the expected real-world mortality rate would require 60 monkeys, far more than the 12 animals he can handle at a time. At 100% lethality, he reasons, future drug and vaccine tests can show statistically significant results using fewer animals.

The monkeys, weighing from six to 28 pounds, were anesthetized -- both for their comfort and workers' safety. "You don't want a monkey who can bite, scratch or get off the table and swing from the water pipes," he says, "when you're holding one billion infectious virus particles."

The sedated animals didn't so much as twitch as five team members oversaw the infusion: Dr. Jahrling, Army drug researcher John Huggins, a veterinary pathologist, an animal technician and an animal caretaker. After securing the animals under protective tents, the five underwent an eight-minute chemical decontamination of their suits, then took soap and water showers.

Now the team is monitoring the disease's downward spiral. "We're not interested in killing monkeys capriciously," Dr. Jahrling says. "Sometimes I sit bolt upright in the middle of the night. Then I remember why I'm doing this. I do have a conscience."

Almost from the moment the new Asian respiratory disease was first identified last month, scientists -- and many ordinary citizens in chat rooms on the Internet -- wondered whether it might have been the work of terrorists. Now medical and military experts say the answer is almost certainly no.

''As a scientist, you never say never,'' said Dr. Steven M. Block, a biologist and germ-weapons expert at Stanford University. ''But every indicator I'm aware of points to a natural outbreak.''

While the cause of severe acute respiratory syndrome, or SARS, has not been pinned down, the leading suspect is a virus from the coronavirus family, and the experts say there are several reasons to think its origins are natural: its birthplace in a region of China long known as an incubator for new kinds of influenza, its relatively low lethality and the individual biology of coronaviruses.

But, they add, that biology makes it menacing in a different way.

Coronaviruses have a singular talent for recombination -- for absorbing bits of stray genetic material. One day, virologists warn, that tendency might suddenly turn a benign coronavirus into a deadly one.

''It has the highest frequency of recombination that we know of for any positive-strand RNA virus,'' said Dr. Susan C. Baker, a virologist at Loyola University in Chicago. ''With high-frequency recombination, you always have potential for a new virus to emerge.'' Now, she added, ''it looks like it's happening.''

Known coronaviruses, in addition to causing the common cold, are suspected of causing diarrheal and other intestinal illnesses in humans. Though bothersome, the ailments are rarely fatal. But coronaviruses have caused major illnesses among cats, dogs, chickens, pigs and cattle.

Experts say the new human coronavirus, if it causes SARS, probably arose when it managed to incorporate similar but foreign RNA, which, like DNA, can make up the genome or genetic code of microorganisms. Such alien RNA would make it a kind of natural hybrid.

Human coronaviruses, said [Dr. Mark Randall Denison (born 1956)], an expert at Vanderbilt University, are like the mild-mannered next-door neighbor with a proclivity for doing the unexpected. ''It's always the quiet ones you worry about,'' he said.

Federal experts echo the university experts. ''I see no reason to believe this is anything other than the emergence of a natural disease,'' said [Dr. Peter B. Jahrling (born 1946)], a virologist at the Army's Medical Research Institute of Infectious Diseases.

Coronaviruses, he added, ''are ubiquitous and are relatively promiscuous'' in their ability to infect different species. Infection of a single host with two different coronaviruses can easily lead to recombination and the emergence of new forms, he said, and ''that's probably what happened here.''

Guangdong Province in southern China, where the illness is believed to have emerged late last year, has dense concentrations of domestic waterfowl in close proximity to pigs and people. Experts say those are ideal conditions for transferring diseases among different species and for the emergence of a new strain of flu virtually every year. ''It's no surprise that other viruses can take advantage of similar mechanisms,'' said Dr. Block of Stanford.

Dr. Richard H. Ebright, a microbiologist at Rutgers University who studies germ weapons, agreed that the Chinese origin of SARS argued against its being a weapon. ''If it had first been detected in New York or Washington, or Kuwait City or Tel Aviv,'' he said, ''then I'd think there'd be strong reason for concern.''

A military expert who disagrees is Dr. Ken Alibek, a former top Soviet germ warfare official now at George Mason University. In his book ''Biohazard'' (Random House, 1999), Dr. Alibek said China had developed biological weapons and had once suffered an accident at a secret germ plant, setting off two epidemics.

SARS, Dr. Alibek said in an interview, might have originated from a similar accident. ''It's a very unusual outbreak,'' Dr. Alibek said. ''It's hard to say whether it's deliberate or natural.'' He added that he knew of no Chinese germ-weapons plants in Guangdong.

Several biologists cited the low lethality of SARS -- it kills somewhere from 3 to 5 percent of its victims -- as evidence of its natural origin. Dr. Block of Stanford noted that the germs and viruses that cause diseases like anthrax and smallpox typically have mortality rates of 25 to 95 percent.

''It's bad,'' Dr. Ebright of Rutgers said of SARS. ''But 3 percent is not the Andromeda strain.''

The experts agreed that pinpointing the disease's place of origin in Guangdong could help settle any doubts about whether SARS is deliberate or natural. In China, a team of scientists from the World Health Organization is trying to discover how the illness started and spread.

Mapping the genes of the suspect coronavirus will also shed light on its origin, biologists said. Genes from a highly dissimilar organism would point to human genetic engineering. ''If they put in genes from Ebola,'' said Dr. Block, referring to a dangerous germ from Africa, ''that would be a dead giveaway.''

The Centers for Disease Control and Prevention in Atlanta, which is leading the American inquiry of SARS, said last week that the mapping, known as sequencing, should be completed by the end of this week or the beginning of the next one.

''The sequencing information will show us right away where it came from,'' said Dr. Baker of Loyola. ''I think it's highly unlikely that anybody could have created this virus.''

Army scientists said yesterday that they had taken an important step toward a possible treatment for the deadly Ebola virus in humans by successfully treating monkeys with the disease for the first time.

In tests of an experimental drug among a few monkeys deliberately infected with Ebola, one-third survived, the scientists reported in the medical journal Lancet.

Ebola infection, which causes severe internal bleeding, is usually 100 percent fatal in monkeys and 80 percent in humans. So a 33 percent survival rate for one of the most virulent diseases known is significant, said the authors, from the Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md.

The drug, derived from hookworms, is being tested in other studies in humans for heart conditions and appears to be safe, the authors said. But they said more research was needed before the drug, known as rNAPC2 for recombinant nematode anticoagulant protein c2, could become an accepted treatment for Ebola.

Experts not connected with the Army research expressed cautious optimism, given the paucity of treatments for Ebola and other hemorrhagic fevers.

''Obviously, this work that got a highly significant decrease in death rates needs to be pursued,'' said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases.

No treatment exists for Ebola, and tests of a vaccine have just begun in humans. Though scientists have had earlier successes in treating the disease in mice and guinea pigs with antivirals, these drugs did not work in nonhuman primates.

In the new study, the scientists injected 12 rhesus macaque monkeys with Ebola virus. Beginning either immediately or 24 hours later, nine received rNAPC2 for 14 days. Three of the nine survived; death was slowed by several days in the other six. All three untreated animals died.

''Our results have great clinical implications, since our treatment approach of Ebola hemorrhagic fever targets the disease process rather than the replication of the infectious agent,'' the team headed by [Dr. Thomas William Geisbert (born 1962)] reported.

Ebola usually starts with a fever and flulike symptoms of malaise, muscle aches, headache, followed by vomiting, diarrhea and a rash. The virus disrupts the blood clotting system in monkeys and humans, leading to abnormal blood clotting and then to severe bleeding and death.

White blood cells known as macrophages seem central to the process by releasing a protein called tissue factor on the surface of the cells. As blood flows, tissue factor forms clots that pave the way for the severe bleeding. Dr. Geisbert, Dr. Peter Jahrling and other team members chose the anticoagulant rNAPC2 because they theorized it would block the harmful effects of tissue factor.

In an interview this week in Dallas, Terry M. Fredeking, a co-author and an expeditionary biologist, said he supplied the raw material used to recreate a protein for the new drug.

''I won't say how long it took me to persuade Peter Jahrling that spit from hookworms might be able to treat monkeys with Ebola,'' said Mr. Fredeking, founder and president of Antibody Systems Inc., a research company in Hurst, Tex.

Mr. Fredeking said the World Health Organization in Geneva had asked team members whether rNAPC2 might be used on an experimental basis to treat people in a current outbreak of Ebola in Congo. That outbreak, which is thought to be waning, has caused 28 deaths as of Dec. 2, according to the W.H.O.

The patent on the drug is held by Dendreon, a small Seattle biotechnology company. Stephen Keane, director of business development, said Dendreon was willing to consider letting the drug be tested in Congo but had not been contacted by health officials. W.H.O. experts on Ebola could not be reached for comment.

Ebola was discovered in 1976 in what is now the Democratic Republic of Congo. The source of the virus in nature is not known. It has spread quickly in hospitals where the staff lacks the masks, gowns and other standard protective clothing needed for isolating an infected patient.

[Dr. Clarence James Peters (born 1940)], an infectious-disease expert at the University of Texas Medical Branch at Galveston who has worked on Ebola, called the new results ''very impressive.'' Dr. Peters said a treatment for the Ebola virus would be even more important than a vaccine.

''Our experience to date shows us that people will resist taking a series of vaccine to protect against anthrax, Marburg, Ebola or other diseases, even if they were readily available,'' he said. ''So successful postexposure treatments are critical.''

Jahrling began his USAMRIID career as an Army Captain and immunologist assigned to the Institute in 1972. He was honorably discharged in 1976 and remained with USAMRIID in a civilian capacity. Currently he serves as Senior Research Scientist, and is the Institute’s principal scientific advisor on issues related to medical defense against infectious disease threats. He holds a Ph.D. in microbiology from Cornell University Medical College in Ithaca, New York.

Jahrling has authored or co-authored more than 160 scientific publications, chiefly in the areas of filovirus and poxvirus research. He has served as a subject matter expert and consultant to numerous agencies including the National Institutes of Health, the National Academy of Sciences, the World Health Organization, the Department of State, the National Security Council, and the Centers for Disease Control and Prevention.

He is the recipient of numerous awards and honors including the Secretary of Defense Medal for Meritorious Civilian Service; the Federal Career Service Outstanding Professional Award; the Department of the Army Achievement Medal for Civilian Service; the Order of Military Medical Merit; and the Joel M. Dalrymple Award for Distinguished Medical Service (awarded by the Association of Military Surgeons of the United States).

USAMRIID, located at Fort Detrick, Maryland, is the lead medical research laboratory for the U.S. Biological Defense Research Program, and plays a key role in national defense and in infectious disease research. The Institute’s mission is to conduct basic and applied research on biological threats resulting in medical solutions (such as vaccines, drugs and diagnostics) to protect the warfighter. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command.

Founded in 1848, the American Association for the Advancement of Science (AAAS) works to advance science for human well-being through its projects, programs, and publications, in the areas of science policy, science education and international scientific cooperation. AAAS is the world’s largest general federation of scientists. Its journal, Science, is an editorially independent, multidisciplinary, peer-reviewed weekly that ranks among the world's most prestigious scientific journals.

Scientists trying to develop vaccines against Africa's deadly Marburg and Ebola viruses are reporting an important milestone, a new type of vaccine that prevents the diseases in monkeys. Successfully immunizing monkeys is an essential step toward producing human vaccines.

Two new vaccines, one for Marburg and one for Ebola, were 100 percent effective in a study of 12 macaques being published today in the journal Nature Medicine. Monkeys given just one shot of vaccine and later injected with a high dose of virus did not even get sick. Normally, all the animals would be expected to die.

The Marburg and Ebola viruses are closely related, and in both people and monkeys they cause hemorrhagic fevers that can be fatal within a week. There is no vaccine or treatment for either disease. Death rates in people can be high, sometimes exceeding 80 or 90 percent.

Angola, where a Marburg epidemic was first detected in March, is still struggling to contain the disease, which has killed 340 of 408 victims. The virus is spread by contact with blood, saliva, vomit or other fluids from sick patients.

The two new vaccines are still experimental, and will not be ready to be tested in people for at least two years. If human trials are successful, products might be ready for licensing five or six years from now, the researchers said. The vaccines would not be used for routine immunization, but would be given to health workers in high risk areas, virus researchers and people who had been exposed to the disease, such as relatives and others in close contact with sick patients. Eventually, it might be possible to combine the vaccines to protect people from both diseases with a single shot.

The new vaccines are not the first to protect monkeys. An earlier one, first proved in 2003, may go into safety studies in people in the United States later this year. Each vaccine has its advocates, and researchers say it is advantageous to have several candidates on the horizon.

The work described in Nature Medicine today was done by scientists from the United States and Canada, led by Dr. Steven M. Jones and Dr. Heinz Feldmann of the Public Health Agency of Canada in Winnipeg, and Dr. Thomas W. Geisbert of the United States Army Medical Research Institute of Infectious Diseases in Fort Detrick, Md.

Dr. Jones said the goal of the research was to provide a vaccine that could be used to stop outbreaks like the one in Angola or to protect people from germ warfare. He and other researchers said that governments and the military developed a strong interest in making vaccines against Ebola and Marburg during the 1990's after a Soviet defector said that Russians had stockpiled the Marburg virus, weaponized it and packed it into warheads for possible use in attacks on cities or battlefields.

"Marburg and Ebola are not as significant threats as smallpox would be, but one could wreak incredible human health tragedies in this country and could probably create a huge economic burden even if the diseases didn't spread like wildfire," said Dr. Peter B. Jahrling, an author of the article and an expert on viruses and bioterrorism who used to work for the Department of Defense and is now a chief scientist at the National Institute of Allergy and Infectious Diseases, of the National Institutes of Health. "But I think a lot of people here also see the humanitarian aspects of providing vaccine to people who need it."

Dr. Cathy Roth, head of the emerging and dangerous pathogen team at the World Health Organization, said: "This work is very interesting, very exciting and very promising. There's a long way to go before this vaccine could be put into people. But we really do hope it is pursued."

To make the vaccine, the scientists used another virus, V.S.V., for vesicular stomatitis virus, which causes a mouth disease in cattle but rarely infects people. They chose it because it has a similar genetic structure to the Marburg and Ebola viruses, and because other researchers have had success with it in developing vaccines.

They altered V.S.V. by removing one of its genes -- the change makes it harmless -- and replacing it with a gene from either the Marburg or Ebola virus. The transplanted gene forced V.S.V. to produce Marburg or Ebola proteins on its surface. The proteins cannot cause illness, but they provoked an immune response that protected the animals.

The monkeys were housed at a high-level biohazard laboratory at Fort Detrick, where the researchers, wearing space suits, watched them intently for signs of illness after they were injected with Marburg or Ebola.

"By Day 6, I have a very good idea of whether it's going to work or not," Dr. Geisbert said. "On Day 6 I was feeling really good. By the time we get to Day 10, if the animals haven't become sick or had any problems, we pretty much know it's worked. It is an incredibly good feeling. All the people on the team are high-fiving. I was communicating with Heinz and Steven every day, two and three times a day. 'How are the monkeys? How are the monkeys?"'

As the team pursues its research, other scientists are moving ahead with the previously developed Ebola vaccine, based on an inactivated version of another type of virus, an adenovirus, which can cause common cold symptoms in people. That vaccine, tested in 2003, also protected monkeys, and studies in people may begin this year.

Dr. Jahrling, who has worked on both types of vaccine, said the government was paying for both approaches to cover its bets. He said he thought a vaccine based on an adenovirus would be ready before one based on V.S.V.

"They've got a runner on third with that one," he said, "and the other guys have a runner on first."

Dr. Jahrling added: "A little competition is good. It accelerates everybody. If nobody's behind them they kind of slow up."

But Dr. Gary Nabel, head of the Vaccine Research Center at the N.I.H. infectious disease institute, who has been working on the adenovirus vaccine, said: "I don't look at it as a race. For me, the adversary is the virus and whatever gives us the best opportunity to defeat the virus is what we need to go with."

WASHINGTON — An acclaimed government scientist who assisted the federal investigation of the 2001 anthrax mailings said Tuesday that he erred seven years ago when he told top Bush administration officials that material he examined probably had been altered to make it more deadly.

The scientist, Peter B. Jahrling, had observed anthrax spores with the aid of an electron microscope at the government’s biological warfare research facility at Ft. Detrick, Md.

On Oct. 24, 2001, Jahrling was summoned to the White House after reporting to his superiors what he believed to be signs that silicon had been added to anthrax recovered from a letter addressed to then-Senate Majority Leader Tom Daschle (D-S.D.).

The presence of silicon was viewed with alarm because the material, if artificially added to the anthrax, would make it more buoyant in air and more capable of penetrating deeply into the lungs.

“I believe I made an honest mistake,” Jahrling said in response to questions e-mailed to him for this article, adding that he had been “overly impressed” by what he thought he saw under the microscope.

“I should never have ventured into this area,” said Jahrling, who is a virologist, referring to his analysis of the anthrax, which is a bacterium. Jahrling’s initial analysis -- and his briefing of officials at the White House -- was first detailed in a 2002 book by bestselling author Richard Preston.

Although Jahrling was careful in 2001 not to implicate Iraq or any other regime in the mailings, others used his analysis to allege that the silicon perhaps linked the letters to Iraqi President Saddam Hussein.

Inhaled anthrax can kill at a rate of 80% to 90% unless patients are treated quickly with an antibiotic.

Jahrling’s comments Tuesday came soon after a congressional hearing at which FBI Director Robert S. Mueller III announced that he was arranging for an outside review of scientific findings that helped the bureau conclude that another scientist at Ft. Detrick, Bruce E. Ivins, perpetrated the deadly mailings. The review is to be overseen by the National Academy of Sciences, Mueller said.

FBI scientists and outside experts hired by the bureau to analyze the anthrax recovered from the mailings announced Aug. 18 that although they had found silicon, it occurred within the spores naturally and was not added.

In challenging those experts, one journalist reminded them that Jahrling, among other scientists, had concluded otherwise.

Some critics of the FBI investigation have asserted that Ivins lacked the skills to have “weaponized” the anthrax with any additive that enhanced its virulence.

At Tuesday’s hearing, a member of the House Judiciary Committee, Rep. Jerrold Nadler (D-N.Y.), pressed Mueller anew about how the silicon got into the spores.

After being informed of the events at the hearing, Jahrling renounced his earlier analysis.

“In retrospect,” Jahrling said, “I believe I was mistaken and defer to the experts.”

[Dr. Bruce Edward Ivins (born 1946)], 62, a civilian bacteriologist for the Army, died July 29 after ingesting a massive dose of prescription Tylenol 3.

Attorneys Ivins had hired to defend him against criminal charges being prepared by the Justice Department have said that they would have won his acquittal if the case had gone to trial.

In 2001, Jahrling briefed a roomful of officials at the White House, including Atty. Gen. John Ashcroft, Mueller and Tom Ridge, President Bush’s secretary of Homeland Security.

The next day, the Washington Post published a front-page article headlined “Additive Made Spores Deadlier” that reported:

“The presence of the high-grade additive was confirmed for the first time yesterday by a government source familiar with the ongoing studies, which are being conducted by scientists” at Ft. Detrick.

The article said that the United States, the former Soviet Union and Iraq were “the only three nations known to have developed the kind of additives that enable anthrax spores to remain suspended in the air, making them more easily inhaled” and more deadly.

At the time, Jahrling was employed as the senior civilian scientist at the U.S. Army Medical Research Institute of Infectious Diseases, within Ft. Detrick.

Jahrling is a past winner of the Secretary of Defense Meritorious Civilian Service Award.

Michael P. Kortan, a spokesman for Mueller, said after the congressional hearing that the FBI was seeking the outside review while maintaining “full confidence in our scientific approach.”

“Consideration of an outside review began before any public disclosure of the scientific aspects of the investigation,” Kortan said.