The Deadly Air

Its a Golden Age for the viruses that live with us. More of these single-minded microscopic barbarians than ever are on intimate terms with humans. Yet they remain largely a mystery at the fringe of life, parasites, neither plant nor animal, what some believe to be the original living organisms. They're so small that only in the past hundred years have we isolated them for study. No one has any idea how many there are, whether their numbers are growing, or how many would kill us in a close encounter. Despite generations of research, we have no sweeping antiviral drug that works the way penicillin fights bacteria. But we are learning the size of the threat--that viruses have a much bigger impact on our lives than we thought. And that no virus has our best interests at heart.

Most viruses, like most sharks, don't harm humans. Some could be useful in gene therapy. But all too many cause sickness, pain and death. And it may be that we're only beginning to realize the range of diseases caused (continued on page 172)Deadly Air(continued from page 98) or encouraged by viruses--not just violent fevers, such as Ebola, but cancer, heart disease, schizophrenia, arthritis and multiple sclerosis. Worse, some scientists believe our attempts to control viruses are backfiring, and that the most cunning mutations are now getting the upper hand.

Some have been hiding in reservoir hosts, biding their time. Others are mutations of viruses once benign. Every so often, monster versions of influenza appear--the worst occurring in 1918, killing more people worldwide than any plague or war in history. The bad news: "We're long overdue for another one," says Dr. David Pegues, epidemiologist at the UCLA Medical Center in Los Angeles. "Serious worldwide flu pandemics typically occur every eight to 10 years. It's been more than 20 years since we've had one." Others agree we could be just a roll of the evolutionary dice from another 1918 flu.

Meanwhile, other new viruses keep arriving at our front door. Adventurous travelers, scientists and road-construction crews now routinely encounter unfamiliar viruses as they prowl jungles and rain forests unexplored decades ago. Then they carry their new companions back to urban populations more dense than ever. West Nile virus has arrived in the western hemisphere. Rift Valley fever, a particularly potent virus, is on the move. The hoof-and-mouth virus, a threat to livestock, broke loose again this spring.

Viruses groomed as military hardware are yet another menace. Once thought too complex for small extremist groups to deploy, modern bioweapons are now one of the most plausible terrorist threats.

Just off the Boat

Our latest unwelcome newcomer is the West Nile virus, which made its U.S. debut two years ago. It may have traveled here in smuggled birds. The first evidence of its arrival was an unusual die-off of crows and other birds at the Bronx Zoo. Mosquitoes contract the virus when they feed on infected birds. Then they pass it along to us.

In its first summer in New York, in 1999, West Nile caused 62 severe cases of encephalitis, killing seven people. Health authorities launched a pesticide-spraying effort to kill the mosquitoes, even closing Central Park one night and postponing a concert of the New York Philharmonic in the summer of 2000. Last year, far fewer humans got sick. Only one died and another remains in medical limbo--a "persistent vegetative state." But West Nile is not going away. It's spreading throughout North America. Researchers expect West Nile to reach California by 2003.

To track West Nile's spread, public health workers first monitored hundreds of live chickens in East Coast states. These feathered members of the Sentinel Chicken Surveillance team were luckier than the canaries whose demise in 19th century mines warned miners that deadly gas was beginning to accumulate. Chickens aren't adversely affected--they test positive but don't die. Even so, their infection rates were low. The death of flocks of wild birds is a better sign of West Nile's geographic presence. Now the Centers for Disease Control encourages local health workers to call when they see, as CDC spokesperson Barbara Reynolds puts it, "birds falling out of the sky."

As killer viruses go, West Nile and other mosquito-borne encephalitis viruses aren't as infectious or lethal as smallpox. Still, a 1986 outbreak of St. Louis encephalitis in Harris County, Texas sickened 28 people and killed five.

"There are lots of reasons to believe West Nile is going to remain a more significant problem than St. Louis encephalitis," says Dr. Lyle Petersen, a West Nile expert with the CDC. "West Nile has much higher levels of virus circulating in infected birds. The potential is greater for the virus to spread faster."

And dying from encephalitis wouldn't be the way to go. Encephalitis causes the brain to swell. If you have a terminal case, you descend through headaches, high fevers and bone-deep weariness to convulsions, madness, coma and death.

Viruses are notoriously unpredictable. Friendlies can turn quickly hostile, and vice versa. The 1918 influenza virus is a horrifying example. It first appeared in Kansas that March as a mild headache-and-fever illness--a three-day flu. But it returned that fall in a deadly new form, striking both in Boston and in the trenches of the Western Front. It became pandemic--a worldwide epidemic--scorching its way swiftly around the globe, killing by some estimates more than 20 million people. In just a few months, it slaughtered the same number of victims that AIDS killed in two decades.

The 1918 virus attacked the lungs, and it wasn't a pretty death. Victims basically suffocated. "Your face turns a dark brownish purple," writes New York Times reporter Gina Kolata in Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It. "You start to cough up blood. Your feet turn black. Finally, as the end nears, you frantically gasp for breath. A blood-tinged saliva bubbles out of your mouth. You die--by drowning, actually--as your lungs fill with a reddish fluid."

Because it was wartime, rumors among the Allies held that the deadly bugs were in aspirin made by Bayer, a German company. Or that the crew of a German U-boat had crept into Boston Harbor and released the disease. In fact, it was a strain of the annual flu that had mutated in a new and hideous way. The strain disappeared as abruptly as it arrived. And despite elaborate attempts to get a good sample of the virus (from frozen corpses of its victims and other means), what made it so deadly remains an enigma.

Who are these Guys?

The word virus derives from the Latin for "venom," which fits its character--if a tiny, faceless, inexorably reproducing zombie can be said to have character. Viruses are remarkably different from other disease-causing agents.

They are highly infectious through airborne contact--the most dangerous threat to public health. Many viral infections are still untreatable. For one thing, it's difficult to kill a virus without killing the cell in which it's hiding. Vaccines rally the troops of your immune system before a virus gains a beachhead in your body--but only if they are matched to a known virus. New viruses can usually have their way with you. And the thing about viruses is that they change--and become new--very quickly.

What significantly increases the danger today is that old viruses are joined by so many new comrades. Greatly expanded air travel and other advances have made it easier for viruses to hitch a quick ride from continent to continent in the body of an unwitting host.

The Lassa virus, a lethal hemorrhagic-fever virus, first appeared in 1969 in areas of Nigeria and Liberia that had been opened to tin and diamond mining. Machupo, or the Bolivian hemorrhagic-fever virus, first showed up during 1965 in an isolated area where agriculture expanded after land reform in the Fifties. Junin, the Argentinian hemorrhagic-fever virus, broke out after corn-growing practices changed in the pampas around 1950. The Oropouche virus got its first big exposure to human hosts in 1960 after Brazil cut a road through the jungle, connecting the coast with the new capital, Brasilia. Within a year, 11,000 people were infected.

Korean hemorrhagic fever, caused by a hantavirus, a virus family that is carried by rodents, was first identified as a new disease among United Nations soldiers fighting in rural areas during the Korean War. Related hantaviruses were then found in Russia, Scandinavia, Europe and, in 1993, in the southwestern United States.

Many of our worst viruses are the new arrivals. HIV apparently leaped species from monkey to man only recently. As far as we know, the first two strains of Ebola--Zaire and Sudan--started killing in 1976. Ebola Reston first showed up in 1989 among lab monkeys near Washington, D.C. Another version of Ebola nearly killed a Swiss researcher working with chimpanzees on the Ivory Coast in 1994.

The latest viruses to jump from animals to man include the Hendra virus, carried by fruit bats. It infected 20 horses and three humans in 1994, killing two men in Australia. In 1998 and 1999, a close relative of Hendra, the Nipah virus, jumped from pigs to humans in Malaysia and Singapore, killing 111 people.

What makes some Viruses so Damned Mean?

Virulence is the measure of how good a virus is at making you sick. Life's meaning for a virus, as for us, is to eat and reproduce. "Its program is simply to embed into another organism and to make that organism make copies of it," notes David Ropeik, director of risk communication at the Harvard Center for Risk Analysis. "That's what it does. It doesn't eat, doesn't crap, doesn't have sex." But viruses can live only briefly outside a host's body or in a similar environment. Some might lie in wait in mouse feces, like the hantaviruses, or be carried for a while in mosquitoes. But they can't hang out by themselves on a toilet seat.

If you become the host for an ordinary flu virus, for instance, you sneeze--spreading the virus to friends and colleagues. If you host Ebola, the blood that eventually wells out of your mouth, nose, eyes and other orifices--what's known as black vomit--is a river of virus. A sick person surrounded by other potential hosts helps viruses procreate and move on. That's why many viruses do well in big cities.

"Humans are at unparalleled densities," says Edward Allen Herre, a staff scientist at the Smithsonian Tropical Research Institute in Panama. "And if any one living thing becomes too common, it becomes an increasingly easy target for devastating diseases. If you have one host lined up side by side with another--genetically and physiologically very similar, if not identical--it's extremely easy for a disease to make the jump from one host to the next. From the viral view of the world, this is a lush carpet of food."

Herre spends most of his workdays on Barro Colorado Island, a nature reserve and research site in Gatun Lake, in the Panama Canal. An evolutionary biologist, he studies what makes diseases deadly.

When living entities (humans or viruses) reproduce, we don't make exact copies of ourselves. The next generation is always different. These mutations typically occur in a gradual drift and, even among viruses, usually don't cause problems. If a host's immune system has seen pretty much the same virus before and has built up antibodies--the in-house disease fighters--the host can handle small variations.

But viruses can be especially sloppy at reproduction. And they replicate quickly. Sometimes viruses undergo a bigger change, a revolutionary moment called an antigenic shift, that spawns a different version of the beast. An antigenic shift can blindside the host's immune system, leaving it completely vulnerable. Many believe that's what happened with the 1918 flu virus.

As a parasite, a virus takes its nutrition from the host's cells. The more nutrients it takes, the more virulent it is--eventually destroying cells and causing disease. In an extreme case, the virus does so much damage that it kills the host.

A virus must strike a balance to survive. If it reproduces so fast that it quickly destroys its host, there had better be another host nearby--or that version of the virus won't be transmitted and the disease outbreak stops. Ebola Zaire, the most deadly of its group, is an example of that process. Highly infectious and with a fatality rate as high as 90 percent, this Ebola can devastate densely populated sites, such as hospitals. But then it often burns out when there are no more potential hosts.

When attractive new hosts are few and far between, less virulent copies of the virus survive to reproduce--because they keep their present hosts alive until they get the chance to move on.

If you're the host, your life can depend on this. Hosts bunched too closely together allow the most aggressive strain, the one that makes you most sick, to survive and move on. That virus multiplies like crazy, bursting host cells, destroying tissue, filling the host and all its bodily fluids with copies of itself. Mean viruses love crowds.

The Terror of Weapons-Grade Viruses

In 1346, Tatar troops conquered Caffa, in present-day Ukraine, by catapulting the infectious corpses of plague victims over the city walls. American and Soviet scientists carried out the most recent large-scale bioweapons-research efforts. Particularly popular among both sides after World War II was the virus responsible for Venezuelan equine encephalitis. "It's exquisitely infectious by aerosol," notes Peter Jahrling, a senior research scientist and advisor to the U.S. Army at Fort Detrick, Maryland. "In fact it was probably the premiere bug developed by most offensive bioweaponeers." Fort Detrick is home to the U.S. Army Medical Research Institute of Infectious Diseases. Until U.S. biowarfare research was officially ended in 1969, Fort Detrick was the U.S. Army's biowarfare center.

The Soviets kept quiet and kept going. Ken Alibek, formerly Kanatjan Alibekov, was first deputy chief of research and production for Biopreparat, the Soviet bioweapons program. Alibek, as head scientist, managed a research effort that spent as much as $1 billion a year and employed more than 30,000 scientists and technicians at its high point in the late Eighties.

Biopreparat made weapons from anthrax and other bacterial diseases. But the better weapon candidates in many cases were the familiar crew of viruses--smallpox, Marburg, Ebola, Lassa fever, dengue fever, Russian spring-summer encephalitis, Machupo and Junin. After the fall of the Soviet Union in 1991, when U.S. scientists saw the Russians' abandoned biowarfare manufacturing facilities, they were surprised. "It really was a factory--which was quite sobering," recalls James LeDuc, an Army officer who directed disease assessment at Fort Detrick and who now heads the CDC's effort to control viruses.

Alibek defected to the U.S. in 1992 and promptly disclosed that the Soviets had secretly brewed tons of weapons-grade smallpox virus. This revelation alarmed international health authorities and made the U.S. think twice about destroying its last specimens of stored virus.

Natural outbreaks of smallpox had been eliminated globally in a vaccination effort, and in 1979, the Global Commission for the Certification of Smallpox Eradication declared that the disease was no longer a threat. A generation of children had gone without vaccinations. Supposedly, only two small samples of smallpox were being held under close guard--in Russia and at the CDC in Atlanta--and they were about to be ceremoniously destroyed. "This was for us an excellent reason to weaponize it," Alibek noted in Biohazard, his book about Soviet bioweapons. The Soviet Union's enemies wouldn't know what hit them and would have no immunity.

Today, Alibek is president of Advanced Biosystems, a subsidiary of a Virginia-based company that develops medical defenses against biological weapons. "Unfortunately, a majority of viruses could be used in biological weapons," Alibek says. For instance, the Soviets were working on an Ebola weapon when he left the country, and in 1990 they had tested one based on Marburg hemorrhagic fever. "If it were wielded," says Alibek, "Marburg would be one of the most horrifying biological weapons ever developed."

Bioweapons this sophisticated can't be made in a bathtub. But genetic engineering has brought the complexities and costs within the reach of terrorist-group budgets. Meanwhile, benign gene-manipulation research could inadvertently add to the threat. In January, for instance, it was reported that two Australian scientists genetically modified a virus in an effort to control mouse and rat populations. Instead of a mouse contraceptive, they created a superlethal virus related to smallpox. The new virus is harmless to humans. But the technique developed could make smallpox more virulent than it already is.

In the early Nineties in Russia, it took only "a few million dollars" to make a weapon in which Venezuelan equine encephalitis genes were inserted into smallpox viruses, says Alibek. It could be equally inexpensive to produce a smallpox weapon today--particularly with the guidance of experienced scientists and technicians.

Which is why Jahrling and others from Fort Detrick have been traveling to Russia as part of an intense U.S. effort to find useful work for former Biopreparat scientists. They hope to prevent a dangerous brain drain--to keep these scientists from taking bioweapons jobs in, say, Iraq or North Korea, or with Osama bin Laden, or from simply selling an ampule of smallpox. No one seems to know what happened to those tons of Soviet smallpox viruses, for example. "A determined insider can always get a virus out of a facility," says Jahrling, who visited the Soviet smallpox facility. "The only apparent security was one pimply-faced kid who looked about 14 and had a Kalashnikov rifle."

But the U.S. can't begin to employ all the former bioweapons scientists. "So the strategy has been to go in and select the best and the brightest," says Jahrling. "We tell them, 'You're the ones who can help us with our problems--and, by the way, you're the ones who we're most worried about migrating to Iraq and showing Saddam how to make a bigger and better bug.'"

Attack

A bioweapons assault would be difficult to spot at first. The microbes would be secretly released in an urban subway, or in the cabin of a commercial airliner, or from a private plane miles upwind of a packed sports stadium.

As long as 10 days after the terrorists had escaped, local clinics would fill with patients bringing familiar complaints--upper respiratory infections and muscle pain, coughing, fever. Particularly in winter, most health care workers would say it was the start of a bad flu season. No one would order sophisticated tests. Most physicians and lab technicians have never seen the viruses that would be used, except perhaps in textbook examples. In any case, tests to detect viruses are harder to perform successfully than those for bacteria.

Last year, a Pennsylvania doctor assessed how likely his colleagues would be to diagnose smallpox if they saw it. He described the symptoms and showed photos of the distinctive smallpox blisters. Only one doctor out of 17 recognized the disease. The others guessed lupus, toxic shock syndrome or other ailments.

But in a bioweapons attack, many patients wouldn't recover from their flu. Emergency rooms and intensive care units would soon be overflowing, as many victims slipped into shock and died. Meanwhile, more new patients would show up. The biowarfare siege would be under way.

Bioweapons--particularly virus-based concoctions--worry many emergency planners more than terrorist explosions or chemical attacks do. Casualties from the latter can overpower a local health care system. Bioweapons like anthrax, spread through inhalation of bacteria spores, can be fatal. But they're basically bombs, onetime events. Emergency measures can catch up.

Viral weapons--contagious from human to human--could create more victims week after week in a diabolical process called sustained transmission. That's why, in some scenarios, biowarriors would prefer to use a virus like smallpox to one like Ebola. Smallpox kills about 30 percent of the humans it infects, leaving 70 percent to spread the disease. Ebola, with a 90 percent fatality rate, is less likely to leave enough victims alive to keep an epidemic going.

"If your objective is to quickly inflict the maximum number of casualties, Ebola is probably the weapon to use," says Jahrling. "And, unlike smallpox, which might turn around and bite you in the ass, Ebola would probably burn itself out." That is, smallpox released in the U.S. could easily spread back to the releaser. "I've never quite understood," Jahrling muses, "why the Russians invest in things against which they can't protect their own people."

Countermeasures

Bioweapons in the hands of terrorist groups became real when the Japanese cult Aum Shinrikyo released poison gas in a Tokyo subway in 1995, killing 12 commuters and injuring more than 5500. In the criminal trials that followed, cult members said they'd also made nine attempts to spread anthrax and botulinum, releasing their genetically engineered bugs from the back of a van and off a building roof. Neither weapon was virulent enough to cause harm. They had also traveled to Zaire, but failed to bring Ebola back to their lab to make a weapon.

Russia, Cuba, China, Libya, Syria, Iraq, Iran, Bulgaria, India, Vietnam and Laos are among nations now thought to have stocks of bioweapons. Alibek believes that most nations that support terrorism either have them or are trying to get them.

"The CDC is obviously interested more and more in bioterrorism," says LeDuc. And the U.S. is preparing to fight smallpox again. The CDC has a $343 million contract with Acambis Inc., a Massachusetts-based biotech company, to build a national stockpile of 40 million doses of a new smallpox vaccine. Acambis hopes its vaccine will be approved in about four years.

Other U.S. preparations are in the works. Operation Topoff was a four-day simulated bioweapons attack on Denver last year. Bureaucrats and the staffs of three Denver hospitals were told that terrorists had secretly released a highly infectious airborne version of the plague in a Denver performing arts center. By the end of the third day, authorities had counted 3700 plague cases in seven states--and 950 "deaths."

The attack "quickly overwhelmed the available resources," reported Richard Hoffman and Jane Norton, two Colorado Department of Public Health staffers, in the CDC publication Emerging Infectious Diseases.

Similar results were found by two researchers at the Henry L. Stimson Center, a Washington D.C.--based think tank. The center surveyed local emergency and public health officials around the country and released a report last October called Ataxia: The Chemical and Biological Terrorism Threat and the U.S. Response. The word ataxia gives you a hint of what they found. It's Greek for "confusion."

The report urged politicians to "grit their teeth and fund disaster preparedness over the long term." It also found that emergency personnel often had better ideas than their national counterparts. One suggestion: To limit person-to-person contact in an infectious-disease attack, health workers could distribute drugs and vaccines from the drive-by windows of fast-food restaurants.

Viral Hot Spots

New viruses emerge all over the earth. But virus watchers keep their eyes trained on China, Southeast Asia and the midsection of Africa. One prominent region on the map begins with the Rift Valley in Kenya, moves west to Uganda and Sudan, and then to Zaire. Viruses that include Ebola Zaire, Ebola Sudan, Marburg, Rift Valley fever, HIV, O'nyong-nyong and West Nile all are believed to have originated here. Lassa and Ivory Coast Ebola popped up in West Africa.

"If you look at the origination sites for the filoviruses, for instance--Marburg and the Ebolas--they're all within seven degrees of the equator," says Jahrling, who himself discovered Ebola Reston in 1989 after it arrived at his Fort Detrick office in a styrofoam picnic basket, leaking big red blotches of blood from monkeys at a nearby test site onto his carpet. The monkeys it had infected and killed had originated in Africa.

New influenzas have different origins. Virologists believe that recent influenza pandemics have come from southern China, where farmers, birds and pigs live in unusually close proximity. Bird viruses can be particularly damaging to humans, but they don't normally jump species directly to us. Bird viruses often infect pigs, however. And pigs can host both bird and human influenza viruses. Many believe the pigs act as mixing vessels for each year's new human influenza strains. And by fall the annual flu season is in progress worldwide.

"If you had a flu epidemic now in a vulnerable population as dense as New York City, Los Angeles, Seattle, Chicago, Moscow, London--it would be horrible," predicts Herre, the Smithsonian ecologist. "In two or three years we could have something as bad as the 1918 flu--probably worse."

So each year, a vast international network tracks new flu virus strains. In the U.S., a committee of the Food and Drug Administration picks the three it expects to do the most damage in this country. Vaccines against them constitute your annual flu shot. In spite of this, about 20,000 Americans die each year from complications of influenza.

Meanwhile, other viruses are on the move. "My job is to investigate exotic hemorrhagic fevers and to quickly shoot them down by whatever mechanism possible," says Ali Khan, an epidemiologist who has spent the past decade traveling to areas of disease outbreaks around the world as a member of the CDC's Epidemic Intelligence Service.

Earlier this year, Khan went to Uganda to help shut down the latest outbreak of Ebola. Last fall, he spent almost 12 weeks in Saudi Arabia and Yemen on what he considers a far more unsettling case--the first epidemic of Rift Valley fever to jump the Red Sea.

"It's a real big deal that Rift has moved to Saudi Arabia," says Khan. "It's the first evidence of Rift off the African continent." This has the attention of both health care and livestock experts. Rift is highly contagious through mosquitoes. But people who handle or slaughter infected animals can also be infected directly. Rift is a rancher's nightmare, killing almost every young sheep, cow, goat, buffalo and camel it infects, and causing pregnant animals to abort. Most humans don't know they've picked up Rift. Some will have severe flulike symptoms. And about one percent of infected people will die of hemorrhagic fever, encephalitis or acute hepatitis.

Khan predicts that Rift Valley fever, if it makes it to the U.S., will be disastrous, particularly to our monoculture livestock--all those identical hosts chewing their cud in the field together. Hosts packed together can increase virulence.

"West Nile's arrival in the U.S. was not a good thing," Khan says. "But it's only led to a bunch of dead crows and a handful of sick or dead people. Rift would be very different if it were introduced here. It would have a major economic impact on us, obviously. And it would infect a lot more people--we're talking millions."

Is Disaster Inevitable?

We're only now learning how much harm familiar, as well as new, viruses can cause. For instance, many of us don't realize that some viruses cause cancer. Yet researchers agree that human papillomavirus is the leading cause of cervical cancer in women and anal cancer in men. And as Paul Ewald, an evolutionary biologist at Amherst College, the National Cancer Institute and others point out, that is only the beginning. Over the past quarter century, medical researchers have found that viruses also produce specific varieties of leukemia, liver cancer, nasopharyngeal cancer, Kaposi's sarcoma, lung cancer and brain cancer. In Plague Time: How Stealth Infections Cause Cancers, Heart Disease and Other Deadly Ailments, Ewald also describes tentative links between viruses and other chronic diseases, including Alzheimer's, autism, schizophrenia, bipolar disorder, Lou Gehrig's disease, multiple sclerosis, breast cancer, some type-II diabetes, some arthritises, stroke, colon cancer and cancer of the penis.

Does this mean we could someday take vaccines against cancer, heart disease, Alzheimer's? Not likely, says Ewald. Vaccines, he contends, have almost all been unsuccessful in the long run--with smallpox the one big exception. The smallpox virus was contained in part because it is transmitted only human to human. By vaccinating everyone in the world, all hosts were eliminated.

"If you can eradicate an organism, do it," Ewald agrees. He believes that vaccines could still wipe out measles and polio. But for most viruses, he contends, vaccines aren't the answer. Viruses mutate too successfully, making end runs around the vaccines, leaving only the "wily" viruses that now pose such a big threat. We need "evolutionary literacy," Ewald says--a focus on smart vaccines and other measures that lower, not raise, virulence.

"Immunologically, you are a very different creature than you were two years ago," says Herre. "We're a moving target, too. And so you have this extraordinary dance through time, between ever-changing hosts and ever-changing viruses."