In 1979, anthrax was accidentally released in the city of Sverdlovsk (pop. 1,200,000) in the former Soviet Union, infecting about 80 to 100 people and killing at least 70. Russian officials claimed at the time that tainted meat sold on the black market was responsible; American officials argued that a nearby biological weapons facility released the killer spores. In the early 1990s, Harvard researchers visited the city to piece together the epidemiology of the outbreak. Their investigation, published in Science magazine in 1994, concluded that the Soviet cover story was false.

Now, physicist Dean A. Wilkening, director of the science program at Stanford's Center for International Security and Cooperation (CISAC), has revisited this Cold War tragedy and used its real-world data to improve our ability to model the medical effects of inhalational anthrax. This, in turn, allows him to model more accurately hypothetical scenarios such as the release of a kilogram of aerosolized anthrax in Washington, D.C., today.

The models researchers have used in such thought experiments "predict very different outcomes," says Wilkening, whose work to better understand the human effects of inhalational anthrax was supported by grants from the John D. and Catherine T. MacArthur Foundation and the Carnegie Corporation. Using real-world data from the Sverdlovsk outbreak and from limited nonhuman primate experiments, he was able to eliminate two of four theoretical models currently used in "what if?" scenarios that inform bioterrorism policies ranging from how much medicine we should have on hand in the Strategic National Stockpile to how rigorous post-attack decontamination efforts need to be. He reports his findings in the May 1 issue of Proceedings of the National Academy of Sciences.

"To date, researchers haven't paid enough attention to which model they use," Wilkening says. "Different models can give predictions that vary by a factor of 10 or more, so it matters which model one uses for predicting the human effects of inhalational anthrax." Wilkening aims to anchor models on the best available data and provide realistic models that the bioterrorism community can employ in policy studies.

The Sverdlovsk outbreak is "a sort of natural experiment," he says. "It's a tragic incident, but it also is a very valuable source of scientific data that one can use to distinguish between the four models currently in use." The upshot of his analysis is that two of the models currently in use are not accurate for predicting the human response to inhalational anthrax.

Insufficient data is available to resolve which of the remaining two models he examined is most accurate. That answer will have to await further data from costly nonhuman primate experiments, should they ever be performed (none are planned). "We have to use both [models] right now, or use them as bounding cases," he advises.

Wilkening explored four policy issues that illustrate the consequences of choosing different models: 1) calculating how many anthrax-exposed people would become infected and how many would die; 2) assessing if decontamination would be needed; 3) determining how soon exposed people would show symptoms and how soon doctors would recognize those symptoms as anthrax; and 4) calculating how soon exposed people need to receive antibiotics to avoid contracting the disease.

"To figure out what happens in a bioterrorist event, you need to know two basic properties about the pathogen you're dealing with," Wilkening says. One is the dose-response curve, which determines the likelihood of becoming infected at different exposure levels--the higher the dose of anthrax you get, the higher the probability that you will become infected. The dose at which 50 percent of an exposed population becomes infected, called the ID50, is around 10,000 spores. The other basic property is the incubation-period distribution, or the time the pathogen takes to grow in the body before symptoms first appear.

Wilkening's study brought dose-dependence to a debate over how long the incubation period is for inhalational anthrax. Published data from vaccine efficacy tests in which nonhuman primates were challenged with high doses of anthrax--up to a million spores--indicate an incubation period of one to five days. Data from Sverdlovsk, which exposed people to low doses probably on the order of 1 to 10 spores, indicate a longer incubation period, about 10 days. Whereas previous authors have debated whether nonhuman primate experiments or the Sverdlovsk data should be used to determine the incubation period for inhalational anthrax in humans, Wilkening demonstrates that both estimates are correct, with the difference between them being due to the dose dependence of the incubation period and the very different doses received in each case.

"If you are exposed to a higher dose, there is a much higher chance that an anthrax spore will germinate quickly, thus leading to a shorter incubation period," he says. "Sverdlovsk was a low-dose exposure event and, consequently, one would expect anthrax spore germination to take a longer time, thus leading to a longer incubation period."

Truth and consequences

Russian officials confiscated the medical records of the Sverdlovsk victims and have so far refused to release details of what happened on April 2, 1979. "It would be nice to know exactly what happened, because that would allow us to model the event more accurately," Wilkening says.

Nevertheless, based on weather and other data from the day of the event, scientists think that around 2 p.m. spores, or dormant cells that revive under the right conditions, were released from a military facility, and the Bacillus anthracis spores spread up to 5 kilometers downwind. People breathed in the spores, which geminated and incubated in the body for between four to 40 days before people began to feel ill or show signs of illness such as sore throat, coughing, pains, aches and runny nose--the same symptoms as flu--that indicated they had entered what doctors call the prodromal phase. Within four days, people passed the point of no return, called the fulminant phase, in which toxins from the bacteria had built up to such an extent that people went into shock and died.

It's impossible to save those who've entered the fulminant phase and difficult to save those who've entered the prodromal phase. But if people can start treatment after exposure but before symptoms appear, there's a good chance that they will survive--a conclusion Wilkening draws from work by colleagues at Stanford's Center for Health Policy. Treatment primarily consists of antibiotics such as ciprofloxacin, doxycycline or penicillin. While a vaccine to prevent anthrax exists, it is not yet available for the general public but would be made available to people exposed to anthrax, according to the Centers for Disease Control and Prevention website.

In his study, Wilkening ruled out two of the four models because they either did not fit the Sverdlovsk data or the nonhuman primate data, or both. "There are two models that people have used that should no longer be used to predict fatalities, models B and C." (The four models used in his analysis are labeled A-D for convenience.)

Using the two remaining models A and D, he predicted that a hypothetical attack releasing 1 kilogram of anthrax spores in Washington, D.C., would infect between 4,000 and 50,000 people, most of whom would die if not treated quickly with antibiotics. The difference of a factor of 10, Wilkening points out, is "an uncertainty with which we must live for the time being until better data can resolve which of the models A or D is more accurate."

Regarding decontamination efforts, the higher the probability of becoming infected at low exposure levels, the greater the need for effective decontamination, especially for indoor environments. Spores "by nature are hardy," Wilkening says. In the soil, out of the way of sunlight, they can last for a decade. "Residual contamination can be a very serious problem in the wake of an attack," Wilkening says. "Unfortunately, both models A and D predict that residual surface contamination from anthrax spores will be a problem. Consequently, we need to come up with effective indoor decontamination strategies."

Analysts such as Professor Lawrence Wein of the Graduate School of Business are considering the issue. Last year, he assessed decontamination and concluded cleaning buildings to make them safe to reoccupy was a billion-dollar proposition.

In addition, the four models make very different predictions about when symptoms would occur. The day after exposure, they predict between 10 and 1,000 people feeling sick, with more people getting sick in the viable versus discredited models.

"In terms of detecting the outbreak rapidly, this is a good thing because it says that doctors could recognize it [sooner]," Wilkening says.

In terms of treating people before they reach the prodromal phase, however, this is a bad thing because people become sick quicker. Wilkening's analysis may help policymakers reassess how fast antibiotics need to reach people. His best model says administering antibiotics by day three saves 90 percent of exposed people. "Today we cannot meet the three-day requirement," he warns.

North Korea's nuclear facility at Yongbyon, which had been "frozen" under international inspection since 1994, was reactivated this January for the production of plutonium. Just last week the North Koreans announced that they intended to use the resulting plutonium to make nuclear weapons, which only confirmed what we always believed.

If it keeps on its present course, North Korea will probably have six to eight nuclear weapons by the end of the year, will possibly have conducted a nuclear test and may have begun deployment of some of these weapons, targeted against Japan and South Korea. By next year, it could be in serial production of nuclear weapons, building perhaps five to 10 per year.

This is a nightmare scenario, but it is a reasonable extrapolation from what we know and from what the North Koreans have announced. The administration to this point has refused to negotiate with North Korea, instead calling on the countries in the region to deal with the problem. The strategy underlying this approach is not clear, but the consequences are all too clear. It has allowed the North in the past six months to move from canned fuel rods to plutonium and, in a few more months, to nuclear weapons. And the consequences could extend well beyond the region. Given North Korea's desperate economic condition, we should expect it to sell some of the products of its nuclear program, just as it did with its missile program. If that happens, a nuclear bomb could end up in an American city. The administration has suggested that it would interdict such transfers. But a nuclear bomb can be made with a sphere of plutonium the size of a soccer ball. It is wishful thinking to believe we could prevent a package that size from being smuggled out of North Korea.

How did we get into this mess?

For several decades North Korea has aspired to have nuclear weapons. During that period successive administrations have, through a combination of threats and inducements, curtailed their program but never their aspirations. In the late 1980s the first Bush administration saw the potential danger and persuaded the Soviet Union to pressure North Korea to join the nuclear Non-Proliferation Treaty and subject its nuclear facilities to international inspection. The North Koreans complied, but they stalled long enough to give them time to make and store enough plutonium for one or two nuclear bombs before the inspectors arrived.

Shortly after the Clinton administration took office, they tried again. As spent fuel was being taken from the nuclear reactor at Yongbyon, the North Koreans ejected the inspectors and began preparations for reprocessing. This would have given them enough plutonium for five or six additional nuclear bombs. President Clinton considered this sufficiently dangerous that he declared reprocessing a "red line." In response, I had the Joint Chiefs prepare a plan to use military force if necessary to prevent this outcome. When Kim Il Sung offered to negotiate the issue, Clinton responded that he would negotiate only if the North Koreans froze all activity at Yongbyon during the negotiation. In the end, military force was not necessary. The agreement that ended this crisis was far from perfect, but in its absence North Korea could today have 50 to 100 nuclear weapons.

But the North Koreans never gave up their desire for nuclear weapons. Even as they complied with the freeze at Yongbyon, they covertly started a second nuclear program at a different location. American intelligence discovered signs of this program and last fall confronted the North Koreans, who did not dispute the charge. The administration responded by stopping fuel oil deliveries called for under the old agreement, to which the North Koreans responded by reopening Yongbyon and racing to get nuclear weapons.

There are three basic approaches for dealing with this dangerous situation. The administration can continue to refuse to negotiate, "outsourcing" this problem to the concerned regional powers. This approach appears to be based on the hope that the regional powers will be able to prevail on North Korea to stop its nuclear program. But hope is not a strategy. If their hopes are not realized and North Korea continues on its present course, it will soon have a significant nuclear arsenal. And while the regional powers could play a role in resolving this crisis, they are unlikely to succeed in the absence of a clear American negotiating strategy in which they can participate.

A second alternative is to put economic pressure on North Korea and hope for "regime change." Or the United States could take military action to bring this change about. But while the regime may one day collapse, with or without economic pressure, there is no reason to believe that it will happen in time - the nuclear threat is imminent. Taking military action to force a timely regime change could result in a conflict comparable to the first Korean War, with casualties that would shock the world.

The third alternative is to undertake serious negotiations with the North Koreans to determine if there is a way to stop their nuclear program short of war. The administration is clearly reluctant to negotiate with the North Koreans, calling them loathsome and cheaters. It is easy to be sympathetic with this position; indeed, the only reason for considering negotiation with North Korea is that the other alternatives are so terrible. The administration, seeing the danger, has said that it "would not tolerate" a North Korean nuclear arsenal. The North Koreans responded to this declaration by accelerating their program. The conflict between our views and their actions is a formula for drifting into war. It is imperative that we stop that drift, and the only clear way of doing that is by negotiating.

Any negotiations with the North Koreans are likely to be difficult and protracted, so they should be predicated on a prior agreement that North Korea will freeze its nuclear activities during the negotiations. For negotiations to have a chance of success, they would need to have a positive dimension, making it clear to North Korea that forgoing nuclear weapons could lead it to a safe and positive future. But they would also need a negative or coercive dimension, both to induce North Korea to take the right path and to give us and our allies more credible options if diplomacy should fail. President Kennedy said it best: "We should never negotiate from fear, but we should never fear to negotiate."

The nuclear regime in place since the Nonproliferation Treaty (NPT) took effect in 1970 is broken and needs to be fixed, the world's highest-ranking nuclear official told a half-full Memorial Auditorium in a wide-ranging lecture about the future of nuclear energy and weapons yesterday afternoon.

"We have a dysfunctional system -- system that cannot endure," said Mohamed ElBaradei, the director general of the International Atomic Energy Agency (IAEA). "We're reaching the fork in the road. Events in the last few years have made it clear that we need to change course."

The big news from ElBaradei's speech was his support for American entreaties to Iran. But the 2005 Nobel Peace Prize recipient also commented on North Korea, India, Pakistan, Iraq, terrorism, disarmament and the future of nuclear energy.

He said there are probably eight current nuclear states, excluding North Korea. He worried aloud that countries which can currently produce nuclear energy peacefully are only six months away from developing nuclear weapons for military purposes.

"Acquiring the technology to enrich uranium or reprocess uranium basically is the key to develop nuclear weapons as we have seen in Asia and Iran," he said. "They are virtually weapons states because in six months time if they decide for security reasons to develop their own weapon, they are there."

Iraq

While not a household name, ElBaradei was a prominent figure in the news as the lead weapons inspector in Iraq during the run-up to the 2003 American invasion. He said at the time that he could not find evidence of Iraqi weapons of mass destruction, but he would not conclude that there were no weapons in the country or that Saddam Hussein did not have a program.

ElBaradei asked for more time to complete inspections, but the Bush administration declined his request and decided to invade. The U.S. never found the nuclear and biological material that some had promised existed.

"Luckily...well I'm not sure luckily...we were proven right that there was no nuclear or any weapon of mass destruction in Iraq," he said. "But I hope that all of us have learned from the Iraq experience that we cannot just jump the gun. You have to be absolutely sure of the facts."

India

ElBaradei surprised observers when he supported the U.S. agreement with India earlier this year, which allowed the country to continue developing nuclear weapons and energy. He said the agreement with India did not endorse its proliferation activities but was indicative of the kind of outside-the-box thinking the international community needs when considering the spread of nuclear weapons and material.

"The end result is India coming closer and working with the rest of the world," he said. "It is not a perfect agreement, but it has a lot of advantages. From the safety, security and nonproliferation perspective, I see that agreement as a win-win situation."

Pakistan

Pakistan developed nuclear weapons as a response to India. Some have criticized Pakistan for its poor stewardship and control of the bomb, pointing out that weapons were almost fired during a skirmish over the disputed Kashmir region.

AQ Kahn, a senior nuclear scientist who helped Pakistan join the exclusive nuclear club, was caught selling compact discs and other information about bombs to several other countries.

"How much damage was done in the process we don't know," ElBaradei said.

The release of this nuclear material demonstrates the need for a "more robust verification system," he said, adding that Pakistan has come closer to the international community in recent years.

North Korea

Kim Jong Il expelled all IAEA inspectors in Dec. 2002, withdrew from the NPT in Jan. 2003 and announced in February 2005 that his military had a nuclear deterrent.

"North Korea is still a major problem," ElBaradei said. "We don't talk about it enough, but North Korea is declaring right now that they have a nuclear weapon. And the longer that they continue to be in that status, the more it is accepted in the collective conscious. This would be terrible because it will have a lot of negative ramifications in South Korea and Japan."

ElBaradei said ongoing negotiations are an important development but more needs to be done.

"What we see with the current six-party talks should have taken place years ago," he said.

Nuclear Proliferation

ElBaradei stressed that he understands the value of nuclear power, which produces much of the developed world's energy. Reducing its use would create more dependence on greenhouse gas-creating fossil fuels, he said.

"We need to use nuclear energy responsibly to maximize benefit and minimize risk," he said.

He said his "number one nightmare scenario" is a terrorist group acquiring nuclear technology since terrorists are not deterred by the possibility of reprisal.

In the post-Cold War world, ElBaradei said he could see no justification for the U.S. and Russia to maintain their nuclear arsenals on ready alert to fire with thirty minutes notice. He called on America to lead by example and continue to disarm its nuclear stockpile.

"Rather than pass judgment, I'd definitely like to say the U.S. should do more in leading by example in terms of nuclear disarmament," he said.

In September 2005, ElBaradei was reappointed to a third term as director general of IAEA. The United States had considered holding up his nomination but dropped its objections under pressure from European allies, who admire the former law professor from New York University.

Diplomat to the Core

The Egyptian native's sometimes broken English was interspersed with self-corrections and careful legalese nuance. ElBaradei answered questions posed by Political Science Prof. Scott Sagan, the director of the Center for International Security and Cooperation.

When Sagan made bold pronouncements about different country's nuclear activities, including the United States' "colossal failure" when North Korea violated the NPT, ElBaradei seemed careful not to point fingers, play the blame game or make enemies. Nonetheless, for a senior United Nations official, his speech was notably blunt.

"There's no international public servant whose integrity and work I admire more than yours," Sagan told ElBaradei.

Accompanied by his wife, ElBaradei spent the day at the University visiting with faculty and students. He spoke at a lunch sponsored by the Freeman Spogli Institute for International Studies and traveled to Sagan's home for a dinner with invited guests. He left the area at 8:30 p.m.

Before attacking Iraq in March 2003, the United States told the world that Saddam Hussein had reconstituted his nuclear weapons program in defiance of the United Nations. That claim, used to justify the war, was based on assessments provided by the United States intelligence community. But as everyone now knows, those assessments were wrong. So Jeffrey T. Richelson's history of American nuclear intelligence, including our attempts to learn about Iraq's nuclear program, could hardly be more timely.

In "Spying on the Bomb," Richelson, the author of several books on American intelligence, has brought together a huge amount of information about Washington's efforts to track the nuclear weapons projects of other countries. He examines the nuclear projects of Nazi Germany, the Soviet Union, China, France, Israel, India, South Africa, Taiwan, Libya, Pakistan, Iran and North Korea, as well as Iraq. Through interviews and declassified documents as well as secondary works, he sets out briefly what we currently know about those projects and compares that with assessments of the time.

This may sound like heavy going, but Richelson writes with admirable clarity. And along the way he has fascinating stories to tell: about plans to assassinate the German physicist Werner Heisenberg during World War II; about discussions in the Kennedy and Johnson administrations on the possibility of attacking Chinese nuclear installations; about Indian measures to evade the gaze of American reconnaissance satellites; and about the bureaucratic infighting over the estimates on Iraq.

The United States has put an enormous effort into gathering information about the nuclear projects of other countries. After World War II it equipped aircraft with special filters to pick up radioactive debris from nuclear tests for isotopic analysis. It created a network of stations around the world to register the seismic effects of nuclear explosions. Most important, in 1960 it began to launch reconnaissance satellites that could take detailed photographs of nuclear sites in the Soviet Union and China. Richelson occasionally speculates about the role of communications intercepts and of spies, but these appear from his account to have been much less important than the other methods of collecting information.

Through these means the United States has gathered a vast quantity of data, sometimes to surprising effect. Intelligence played a crucial role in the cold war, for instance, by reducing uncertainty about Soviet nuclear forces. Alongside such successes, however, there have been failures. One notable example concerned the first Soviet test, which took place in August 1949, much sooner than the C.I.A. had predicted. Another was the failure to detect Indian preparations for tests in May 1998, even though at an earlier time the United States, with the help of satellite intelligence, had managed to learn about preparations the Indians were making and to head off their tests.

But the most serious failure of all was in Iraq in 2003, because in no other case did the intelligence assessments serve as justification for the use of military force. The information needed for avoiding political surprise is one thing. That needed for preventive war is quite another, if only because of the consequences of making a mistake.

Beyond making the uncontroversial recommendation that "aggressive and inventive intelligence collection and analysis" should continue, Richelson draws no general conclusions. That is a pity, because his rich material points to issues that cry out for further analysis. He suggests in one or two cases that failures sprang from the mind-set of the intelligence community, but he does not elaborate on this point. He has little to say about relations between policy makers and the intelligence community, even though the quality of intelligence and the use made of it depend heavily on that relationship.

His focus is no less narrow in his discussion of foreign nuclear projects. He concentrates on the programs themselves, paying very little attention to their political context. Does that reflect a technological bias in nuclear intelligence? Would, for example, the prewar assessment of Iraqi nuclear capabilities have been more accurate if it had paid more attention to the broader political and economic circumstances of Hussein's regime?

The task of intelligence has become more complex than it was during the cold war. A single dominant nuclear opponent has now been replaced by a number of nuclear states, along with states and stateless terrorists that are aiming to get their hands on nuclear weapons. Meanwhile, the technology needed for producing nuclear weapons has become easier to acquire.

Many critics believe the recent performance of the intelligence community shows it has not responded adequately to this new situation. Richelson does not have much to say on this question; nor does he discuss the likely impact of the current reforms, initiated in response to the Iraq war, on the quality of intelligence. His reticence may imply that he does not think reform is necessary. Still, it is disappointing that he does not draw on his historical survey to discuss whether new approaches are needed for dealing with nuclear threats, and, if so, what those new approaches might be.