Part of a series investigating the complex links between human, animal and environmental health: The Infection Loop.
In early October 2001, just days after Bob Stevens hiked through North Carolina's Chimney Rock Park and drank from a waterfall, government officials were retracing his steps. They were desperate to know why the 63-year-old man lay gravely ill in a Florida hospital. His diagnosis: anthrax.
"We scratched our heads," says Dr. D.A. Henderson, who served as the first director of the U.S. Office of Public Health Emergency Preparedness following Sept. 11. While anthrax can thrive in nature, and has been known to kill livestock, human exposure is very rare. Nevertheless, officials searched for evidence of this bacterial disease, covering a trail between Stevens' herb garden in Lantana, Fla., and an Irish Pub in Charlotte, N.C. Nothing surfaced. It wasn't until several days later, when more anthrax cases popped up in New York City, that it became clear that this was an unnatural and deliberate attack -- delivered via a tainted letter.
Stevens' death marked the country's first known casualty of bioterrorism. Yet the attack was hardly the first use of a living weapon.
Biological weapons have a long and sordid history, from catapulting infected corpses to dropping bombs of plague-infected fleas. But what if a biological weapon were being developed and studied by scientists that had the potential to kill not a battalion or a city, but 150 million people? According to some public health and defense officials, that is exactly what we're facing, following the cultivation of a highly contagious form of H5N1 -- a lethal bug better known as bird flu. The contagion, they fear, could escape the lab or its recipe could land in the wrong hands.
This work being done in labs in Wisconsin and the Netherlands could also be carried out by nature itself, experts point out. And a super flu is just one of a growing list of potential pandemics that could develop in the near future, either as a result of terrorism, of superbugs leaping from animals to humans, or both.
In fact, nearly 80 percent of the bioterrorism agents recognized by the U.S. government started in animals. "Many of them were considered for use as such agents only after they emerged from nature as a result of transmission from animals to humans," says Dr. Thomas Monath, who formerly headed a CIA advisory group on ways to counter biological attack. "And nature will spawn new agents continuously."
This means a terrorist may need few tools, little training, minimal money and no published blueprint to harvest a superbug and then unleash it in food, water, air or via insect vectors such as fleas or mosquitos. "As a normal person, you can collect anthrax in Texas soil or ebola in Africa by hunting down a monkey," says Ramon Flick, chief scientific officer at BioProtection Systems Corp., which develops anti-viral vaccines. "It's so easy to get a potential bioterror agent in your hands."
The overlap of bioterrorism agents and emerging infectious disease also means that officials could defend against biological attacks and natural outbreaks in tandem. Laura Kahn, a research scholar at the Woodrow Wilson School of Public and International Affairs at Princeton University, recalls being "dumbstruck" when she made the realization.
"It seemed like this was a case where we could really kill two birds with one stone," she says.
However, no sooner had the realization been made than federal funding cuts began to threaten U.S. efforts to predict and control potentially lethal outbreaks.
CLEAR AND PRESENT DANGER
At the United Nations last September, President Barack Obama spoke of the need to "come together to prevent and detect and fight every kind of biological danger, whether it's a pandemic like H1N1, or a terrorist threat, or a terrible disease."
In December, at the Seventh Review Conference of the Biological Weapons Convention, Secretary of State Hillary Rodham Clinton got more specific. Al-Qaida, she said, was known to be seeking "brothers with degrees in microbiology or chemistry to develop weapons of mass destruction."
"There are warning signs," added Clinton, "and they are too serious to ignore."
Yet federal funding to prevent and respond to bioterrorism is plummeting. The U.S. Centers for Disease Control and Prevention's biodefense budget peaked in 2005 at about $1.2 billion. The 2012 budget is down to $800 million, with state and local programs -- the country's first line of defense -- absorbing some of the most significant cuts.
"We haven't had enough resources to do as much training. It's taking longer to revise plans so they may not be as current." says Jane Braun, director of the Office of Emergency Preparedness at the Minnesota Department of Health. "It's hurting our ability to respond as rapidly and as effectively. And this is true for all states."
Over the last decade, Minnesota has provided outreach to local labs, including hands-on training for germs that are rarely seen. Every year, the state highlights four or five new organisms.
The effort has paid off. Last August, an individual traveling through Minnesota landed in a rural hospital that had participated in the training. Workers quickly recognized the culprit as anthrax -- in this case, naturally acquired -- and "saved the guy's life," says Maureen Sullivan, also of the Minnesota Department of Public Health and chair of the Public Health Preparedness and Response Committee for the Association of Public Health Laboratories.
Sullivan is now working with less than half of the lab funding she received from the CDC in 2003. The cuts mean less hands-on training, fewer organisms, and inconsistent coordination between state and local labs. "The general public, and I could go as far as saying politicians or the people with the money, don't really realize the importance of sustaining the infrastructure we've created," Sullivan says.
Further, the Biomedical Advanced Research and Development Authority receives about 10 percent of the funding it needs to develop antibiotics and other medical defenses, according to the bipartisan Weapons of Mass Destruction Terrorism Research Center.
"A bio-response enterprise without adequate medical countermeasures is like an Army without bullets -- it may look good on a parade ground, but has minimal value for national security," says an October publication from the center. The center's "report card" concluded that the U.S. "remains largely unprepared for a large-scale bioterrorism attack or deadly disease outbreak."
None of this is to say the the U.S. hasn't improved bioterrorism preparedness since the 2001 anthrax attacks. The subsequent surge in funds has gone a long way.
"We've made a lot of progress," says Dr. Ali Khan, director of the CDC Office of Public Health Preparedness and Response. "But that progress is in jeopardy."
Some of the progress also turns out to be a double-edged sword. The rise of biotechnology is a case in point.
In January, the Dutch and American researchers behind the two widely-discussed H5N1 papers, along with dozens of other flu experts, voluntarily halted bird flu research to give the world time to digest and discuss the dangers.
As its name suggests, the virus mainly affects birds. Sick birds have infected human handlers on rare occasions, but the inability of the virus to jump directly between humans has kept outbreaks from becoming pandemics. In the two not-yet-published studies, scientists tweaked the virus so it could spread easily among ferrets, a popular stand-in for people in flu research.
In an editorial published in late-January in the journal Science, Ron Fouchier and his Dutch co-authors argue that their bird flu research and its publication are crucial for understanding what traits to look for if (or more likely, when) the virus mutates into a more contagious, deadly or drug-resistant bug -- with or without human help. Such knowledge could help contain dangerous viruses in the future. The public health benefits, they wrote, far outweigh the risks.
The scientists are also far from alone in their tinkering. "To a certain extent, the genie is out of the bottle," says Dr. Scott Lillibridge of Texas A&M, formerly the founding director of the Bioterrorism Preparedness and Response Program at the CDC. "We have moved from dozens of labs when we started biodefense in the U.S. to probably thousands of labs [worldwide] that dabble in genetic manipulation."
Greg Koblentz, a biosecurity expert at George Mason University in Virginia, adds that labs around the world are inconsistent in their safety and security standards. Nevertheless, he says that "we still shouldn't be going around making new versions" of deadly viruses without fully considering the possible implications.
Even in the U.S., decreasing funds are making it more difficult to maintain safe and secure facilities, says Minnesota's Sullivan. New regulations are in the works to require labs using certain biological agents to implement safeguards including psychological evaluations for employees. But the added cost has led many states to consider dropping out of the program altogether, Sullivan says.
Meanwhile, nature knows no rules or regulations and continues to create new viruses and alter old ones. And because animal-borne diseases may need no help spilling over into humans, outbreak investigations could easily confuse intentional and natural outbreaks.
A 1999 New Yorker article quoted an advisor to the FBI who was looking into the possibility that West Nile had been deliberately introduced into New York -- a hypothesis later dismissed: "If I was planning a bioterror event, I'd do things with subtle finesse, to make it look like a natural outbreak," the advisor said. "That would delay the response and lock up the decision-making process."
It took the CDC and the FBI several days to confirm the 2001 anthrax attacks and to inform the public. At that point, "it was a madhouse," says Henderson, now a distinguished scholar at the Center for Biosecurity of the University of Pittsburgh Medical Center.
He recalls everything from talcum powder to women's facial powder arriving at labs for testing. "The worst," says Henderson, "were the powdered donuts."
In all, 22 people got sick and five died. Things could have been much worse. The same quantity of dry-powdered anthrax released into the ventilation system of the World Trade Center could have killed far more people than the airplane attacks did on 9/11, according to a 2006 statement from Dr. Margaret Hamburg, the current FDA Administrator.
When Henderson took charge of the new public health preparedness operation following the World Trade Center attacks, he learned that intelligence warned of a possible second event, this one biologic. Henderson says that he had already been trying to persuade people that the country should be concerned about biological agents, but was confronted with little interest. "People thought it was morally repugnant to even think about it," he says.
That ignorance remained widespread; Henderson witnessed the consequences. As people evacuated from buildings in response to the anthrax attacks, he explains, many were taken into back lots to be hosed down: "That does no good. Not for a biologic agent."
Despite the chaos, the nation quickly returned to complacency.
The potential for another attack of anthrax or other lethal living agent remains high today. Henderson warns that it is "entirely possible and likely" that a "relative amateur" could pluck strains from the environment that would be just as virulent as the anthrax used in the mailings.
Elin Gursky, a health preparedness policy expert at the public-service research institute ANSER/Analytic Services Inc., also highlights Iran's biological weapon program and the host of emerging pathogens. "Anyone that turns a blind eye to these threats perplexes me," she says.
Gursky calls the current "erosion" of funding "insidious."
When an estimated 100 people died of anthrax near Sverdlovsk (now Ekaterinberg, Russia) in 1979, the Soviet government blamed the environment. Anthrax was endemic to the area, so it was plausible that the local meat became contaminated by livestock grazing in a pasture naturally laden with the spores.
Years later, however, American scientists called the Soviets out on their deliberate misrepresentation -- and their violation of the 1972 Biological Weapons Convention, a treaty that bans these weapons.
By mapping both human and animal cases, and the direction of the wind, U.S. scientists established the path of the airborne agent and concluded that the so-called "biological Chernobyl" had actually originated from a secret military facility, says Dr. Peter Rabinowitz, an environmental medicine expert at the Yale University School of Medicine.
The accidental release of anthrax killed animals over a far wider range than it killed people who breathed the spores. This is not surprising, given that livestock spend more time outside and have greater susceptibility to anthrax than humans. But the implications could be powerful. If local farmers and veterinarians had recognized the animal infections and shared their findings with medical doctors, early courses of antibiotics may have saved human lives.
"The government spends a lot of money developing biosensors," says Princeton's Kahn, referring to air sampling surveillance and other sophisticated systems. "But I would argue the best ones are flying around," or in this case, hanging out on farms.
Zoos can be particularly good sources of sentinels, she adds, as they house a wide array of animals from around the world with different levels of susceptibility. Most zoos are also located near densely populated urban centers, which tend to be terrorism "hot spots."
"There's a possibility that the high-tech tools are not even in the right place," says Rabinowitz. "By being constantly aware of new events in animals as well as in humans and the environment, we're more likely to pick up a new threat."
The strategy could address the risk of a less direct terrorist attack, such as the exploitation of a vulnerable water or food system. Plants and animals have little or no innate resistance to foreign pathogens, and are not vaccinated against the bugs. Regardless of whether the agent spills over into humans, losses could easily run into the billions of dollars.
"The means of efficient dissemination by a terrorist would not involve complex delivery systems -- just a needle and a cow in a pasture," says Monath, now an adjunct professor at the Harvard School of Public Health.
Koblentz, of George Mason, says he doesn't see such "subtle" attacks lining up with a terrorist's M.O., or the "idea of getting attention towards a cause and coercing the government to change its behavior." But he does agree with the need for broad surveillance.
"If we only start paying attention when people are dying, at that point it's too late," says Koblentz.
ARE WE 'READY FOR ANYTHING'?
This emphasis on coordination among medical, veterinary and environmental health scientists, reflecting the global "One Health" movement, could also be employed in the development of vaccines and treatments for bioterror threats.
Rift Valley fever virus is a prime candidate for such collaboration, says BioProtection Systems' Flick, an expert on emerging infectious disease, which can afflict both animals and humans. Creating a livestock vaccine would reduce the risk of human infection.
However, because the disease is not considered a priority human bioterrorism agent by the government, research funding is low. Jason McDonald, a CDC spokesperson, explains the agency's exclusion of Rift Valley: humans typically contract the virus through bites of infected mosquitoes and just 1 percent of these victims die.
The public's current awareness of Rift Valley fever and its perception of the West Nile virus threat before 1999 are strikingly similar, he says. West Nile had not been given much thought before it cropped up in New York City. Within a few years it had spread across the country.
Flick warns of even more devastating consequences with the relatively unknown bug. More mosquito species can carry Rift Valley than West Nile. It is also more virulent. And according to research in Arabia and Africa, the fatality rate may actually be increasing, killing more than 30 percent of people infected during recent outbreaks. Further, there does appear to be potential for human-to-human transmission.
Shortly after the anthrax attacks, experts convened to draft a federal priority list of bioterror agents based on what they perceived as the country's greatest vulnerabilities. Among the top-ranking bugs: anthrax, smallpox and plague.
"We had no ability to know what terrorists would really do," says Scott Lillibridge, who chaired the committee and is now at the Texas A&M Health Science Center. The list was supposed to be temporary, he says, merely helping states and local groups best allocate their first rounds of biodefense funding.
"I don't think it's current," Lillibridge says. He suggests the need to move beyond targeting specific agents towards a broader look at all pathogens, adding that "you've got to be ready for anything."
The CDC's Khan agrees. "If your mind is set on anthrax or smallpox, and you think that we have more than enough vaccine to protect every American, then you might say, 'OK, we're done. Let's close up shop and move on,'" he says. "But we'll never be done with the list of these new agents that show up every day."
Researchers have discovered an average of 15 to 20 previously unknown diseases in each of the past few decades, including incurable diseases like HIV/AIDS, ebola and SARS, with new pathogens likely to emerge and spread faster due to the global population's increasing size and mobility.
GLOBAL HEALTH SECURITY
Lillibridge recalls his time in China during the SARS epidemic of 2003. "I was back home [in the U.S.] within 19 hours from Beijing," he says. "I easily could have been incubating something."
At the time, scientists had not yet identified the newly emerging pathogen, which meant no diagnostic tests.
The ability to detect and identify diseases as they initially emerge can go a long way in thwarting an outbreak, he says. It can provide the time to prepare, including upgrading quarantines at the border, researching a vaccine and identifying what drugs might successfully combat the infection.
"A couple weeks can be critical," says Lillibridge. "It can make an administration look foolish or like they're in control."
Overall, the U.S. government spent approximately $60 billion on biodefense from 2001 to 2009. Only 2 percent of that was dedicated to preventive measures such as programs to discover and reduce biological threats overseas, according to Koblentz.
"To protect Americans, we must look at what is going on in the rest of the world," says Khan.
ANSER's Gursky, recently returned from hosting a NATO meeting in Central Europe. "The most important strategy is to be build up the capabilities that we share, which means reaching across borders and politics," she says.
Meanwhile, the domestic coordination that President Obama spoke of in September is still lacking, some experts say. As with terrorism before 9/11, there is no single agency coordinating biosecurity efforts. Lillibridge suggests it's about time for a focused biodefense center, "a functioning unit where you have lab, surveillance and all these programs aligned."
Coalescing efforts might also allow the government to do more with less. "We're looking at not only man being a terrorist, but nature can be a terrorist as well," says Henderson. "The natural occurrence of a disease gives us similar problems, so whatever we're doing to prepare for one, prepares us for the other."
CORRECTION: A previous version of this article misnamed a CDC spokesperson as Jason Henderson. The correct attribution is Jason McDonald.