Amid Threats of Bioterrorism

US officials, experts debate over smallpox vaccination

By William J. Broad

Intense debates in the Bush administration over smallpox vaccinations have delayed critical decisions in the nation's program against germ terrorism for months, participants say. They say officials, including at times Vice President Dick Cheney, have argued that the nation should move quickly to vaccinate widely even in the absence of a bioterrorist attack. But others, including President Bush, have been more cautious, worrying about the vaccine's risk of causing serious illness or death.

    The result has been confusion and delay, even as preparations for some immunizations move ahead.

    The hesitancy reflects the magnitude of the issue and the difficulty of resolving it, given the uncertainties over whether the United States faces a smallpox attack and how the population would respond to the hazardous vaccine, both physically and emotionally.

    Still, emergency plans are advancing. The Pentagon is completing plans to vaccinate up to 500,000 troops. In September, federal health officials sent the states a detailed blueprint for preparing to vaccinate all Americans.

    Moreover, the upholding of mass vaccinations as a viable option was a large expansion from the modest plans endorsed as recently as few months ago. The about-face has caused government officials, health experts, and the public alike to pay new attention to questions about smallpox, the vaccination that prevents it, and the likelihood of its use as a weapon.

    A disease of high fevers and open sores contracted by inhalation, smallpox was one of humanity's great scourges. Until it was declared eradicated in 1980, it killed up to a third of those who contracted it-as many as 500 million people died in the 20th century alone.

    Today only the US and Russia have publicly declared stocks of the virus. But if clandestine supplies exist-and terrorism experts say they do-smallpox could put all of the US at risk. American officials fear that Iraq may have the smallpox virus and might use it. That, officials say, is a crucial factor driving the Bush administration's accelerated planning for smallpox defenses.

    Caught between worries about vaccination side effects and Iraqi germ attacks, Washington is preparing for wide protections and quietly encouraging allies to do the same.

A Deadly Float

    American officials worry about smallpox because they know that the US and the Soviet Union prepared decades ago to use the virus as a weapon. Moscow made a liquid, Washington a powder, said Jonathan Tucker, an arms expert and author of Scourge, a book on smallpox. Smallpox virus weaponized this way can float in the air over long distances, potentially infecting thousands of people.

    As doctors were redoubling a global effort to eradicate smallpox from the wild, an effort that succeeded in 1980, Soviet scientists secretly developed the means to make 100 tons of smallpox a year. In one Soviet field test, American and Russian experts say, the virus escaped and sailed nearly 10 miles over open water to start an outbreak.

    After the Soviet Union collapsed in 1991, many Soviet smallpox experts found themselves impoverished, leading Western experts to fear they might be tempted to sell the virus or their knowledge of how to weaponize it, or both. In 1994, the Defense Intelligence Agency cited an unidentified source as saying Russia had shared smallpox technology with Iraq and North Korea in the early 1990s.

    But Iraq could have developed its own supply of the virus from a natural outbreak that struck there in 1971 and 1972, infecting at least 800 people. "It is most unlikely that Iraq would have missed the opportunity," Richard Spertzel, a microbiologist who in the 1990s led the United Nations biological weapons inspections of Iraq, told a House committee in December.

    Biologists say growing the smallpox virus would be easy for Iraq or any group familiar with basic microbiology. It multiplies readily in chicken eggs and can be harvested on a large scale. Any state or group proficient in germ warfare could turn it into a weapon.

    No smallpox detectors exist. So if a smallpox attack occurred, the authorities would probably learn of the strike in two weeks or so-the disease's incubation period-when sick people started to exhibit symptoms and head for clinics and emergency rooms.

    Vaccination against smallpox can be effective after exposure to the virus, but only up to four days afterward, so it would come too late for the first wave of victims. For them, doctors would have little to offer but comfort as the disease ran its course.

    At a Senate hearing in July, Richard Butler, who from 1997 to 1999 directed the UN hunt in Iraq for weapons of mass destruction, called the possibility of Baghdad's having smallpox a "a deeply disturbing" issue that required "urgent attention."

Vaccine Stockpiles and Outbreak Plans

    As worries about germ terrorism grew in the late 1990s, Washington began a low-profile program to rebuild national stocks of smallpox vaccine and update vaccination plans.

    When routine smallpox vaccination ended in the US in 1972, only 15.4 million doses were left. In 2000 the Centers for Disease Control and Prevention contracted with Acambis of Cambridge, Massachusetts, for 40 million more, at a cost of $343 million. After the September 11 attacks, that effort expanded, with the goal of having enough vaccine for every American, by late this year or early next.

    The plan has old and new elements. Clinical studies showed that the 15.4 million Dryvax doses could be diluted five times to yield 77 million doses. To that would be added 209 million new doses by Acambis Baxter, making a total of 286 million-enough for every American.

    Meanwhile, the drug company Aventis Pasteur disclosed that it had, in cold storage, an additional 75 million to 90 million old doses, which officials now view as an emergency backup. Studies are under way to see if they, too, could be diluted.

    As the stockpile took shape, Bush administration experts and officials began to clash who should be vaccinated and when. The most pressing issue was preattack immunizations of emergency personnel and doctors who would vaccinate wider groups of people.

    Officials said President Bush and Vice President Cheney eventually became deeply involved in the disputes, with Mr. Bush hesitant and Mr. Cheney more willing.

    Minimalists argued for vaccinating only 15,000 health workers, citing the vaccine's dangerous side effects and the June recommendations of the effects and the June recommendations of the Advisory Committee on Immunization Practices (ACIP), a panel reporting to the federal government that made that suggestions.

    On the other side, maximalists by July were pushing for 500,000 individuals or more, arguing that a sizable number of protected people would be needed in the event of serious outbreak. Officials at the time said an announcement of that number was imminent.

    Complicating the decision were doubts about "ring vaccination," the tactic used to eradicate the disease, in which health workers would isolate infected patients and vaccinate people around them. But critics of the approach argued that while ring vaccination worked with natural outbreaks, it would be ineffective in an attack involving thousands of people infected simultaneously.

    Douglas Holtz-Eakin, chief economist at the White House Council of Economic Advisers, went so far as to argue that a major attack could virtually cut down the economy and cost $177 billion a week. At a public meeting in June, he asked if even truck drivers and airplane pilots should be vaccinated.

The Side Effects

    The immunizations for most diseases are made with dead or crippled germs. By contrast, smallpox vaccine is made with a live virus, a smallpox relative called vaccinia, that can multiply aggressively in people with impaired immune systems, cancer or certain common skin conditions.

    When vaccination was routine, complications from vaccinia killed about one person in a million and struck one in 10,000 with serious skin infections, brain inflammations and other ills. Since routine vaccination halted, millions of Americans have contracted the AIDS virus, which can suppress the immune system, and some 200,000 others take immunosuppressive drugs because of organ transplants. Also, rates of skin disorders like eczema are much higher now.

    People with eczema, or even a history of it, are at risk for a condition called eczema vaccinatum, which can produce high fever, a severe rash, scarring and even death. Patients whose immunity has been lowered by illness or by medicines used to prevent transplant rejection have an increased risk for a potentially fatal reaction known as progressive vaccinia, in which the sore that normally forms at the vaccination site expands abnormally, damaging tissues all over the body.

    Pregnant women, babies and patients with cancer and autoimmune disease like lupus are also at risk for severe reactions.

    Even if they are not vaccinated themselves, vulnerable people can be infected by someone who has recently been vaccinated, since the live virus can be shed from the sore at the vaccination site for weeks. So health officials are looking at special bandages to keep shedding to a minimum.

    Many experts contend a drug called vaccinia immune globulin, or VIG, can counter some adverse reactions. Obtained from the blood of vaccinated people, it contains antibodies that the immune system forms to combat germ invaders.

    Few people have been vaccinated in recent years, and the nation has only enough VIG to treat up to 700 patients. At a cost of about $100 million, the government recently contracted with a Canadian company, Cangene, to produce thousands of doses of VIG by late this year or early next.

    But VIG's effectiveness has never been tested in a rigorously controlled study. Dr. John Modlin, ACIP chair, said he was skeptical that it worked. "It seems to me an important issue if we are going to spend tens of millions of dollars" to build up a supply, Modlin said.

    Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the government was making more of the drug "because you don't have anything else."

    So officials are hunting for a safer vaccine. One is a modified vaccinia called MVA, which has an unusually low rate of adverse reactions. In late July the government asked companies to submit proposals for developing the vaccine and producing up to 30 million doses.

    That effort will take several years, Fauci said, adding that MVA "is not in the Iraq picture."

    A more futuristic alternative is antivirals, an emerging class of drugs that fight viruses directly. One, known as cidofovir, is undergoing federal study in animals to see it can help allay side effects of smallpox vaccination or perhaps even fight the disease itself. That would be a breakthrough, making treatment possible for the first time and possibly saving many lives.

    Because cidofovir has to be injected and can damage the kidneys, the National Institute of Allergy and Infectious Diseases is supporting research to develop a form that can be taken by mouth, making administration easier and possibly safer. The findings are encouraging. With reports from Lawrence Altman and Denise Grady