The first in a series investigating the complex linkages between human, animal and environmental health: The Infection Loop.
Bronx Zoo pathologist Tracey McNamara started to see lifeless crows dotting her zoo's grounds in mid-August 1999. After Labor Day weekend that year, she recalls, "All hell broke loose."
Even as crows kept falling from the sky, Chilean flamingos, laughing gulls and a snowy owl, among other captive species, also suddenly began dying. "Many of these birds were healthy at breakfast and dead by dinnertime," says McNamara, now a professor of pathology at Western University of Health Sciences in Pomona, Calif.
Among the casualties was the zoo’s mascot, a bald eagle named Clementine. A necropsy showed the worst brain inflammation in a bird that McNamara had seen in her 18-year career, and she fretted that her surgical mask wasn’t enough protection against whatever had killed Clementine.
"I got a sinking feeling in my stomach, the hair stood up on the back of my neck and I went home and wrote my will," she says.
McNamara became convinced that the surge in bird deaths was tied to the growing reports of New Yorkers sickened or dying with similar signs of muscle weakness and confusion. The Centers for Disease Control and Prevention reported that mosquito-borne St. Louis encephalitis was the killer, but she was skeptical, since that virus doesn't kill birds.
In fact, New York was seeing the first cases of West Nile virus ever reported in the Western hemisphere. Ultimately, 62 people were hospitalized in New York for West Nile that year and seven died. The CDC later admitted it erred by dismissing the potential link between the human and animal illnesses.
Twelve years later, are we preventing, preparing or monitoring possibly epidemic new diseases in adequate fashion? According to specialists who track seemingly exotic public health threats, the answer is no. Our proximity to migrating animals, rodents and livestock, combined with environmental upheaval, has created conditions that make animal-borne epidemics more likely –- a theme the new film "Contagion" embraces with enough zeal to throw Gwyneth Paltrow into a fit of lethal convulsions.
Animals carry a number of viruses, usually without consequence to themselves, but those same viruses can prove deadly to another species. Humans have simply yet to cross paths with most of these pathogens.
"In the future, we're going to come across viruses that have been around for millions of years in obscure animals," says Peter Daszak, president of EcoHealth Alliance, a New York-based organization of scientists dedicated to conserving biodiversity.
While science can typically track down creatures that are hosts to threatening viruses, such human factors as population growth, income inequality, environmental degradation, climate change and even global travel may all play a much more decisive role in unleashing outbreaks of deadly and hard-to-control diseases.
"Microbes are out there and they are paying attention," says James Hughes, a professor of medicine and public health at Emory University, who spent about three decades with the CDC. "They are pretty good probes for weaknesses in the public health system."
Just look around, analysts warn. As deforestation and development shrinks the margins between civilization and the untrammeled regions globally, diseases will have more opportunities for transmission to humans.
Intensifying agricultural production can also facilitate epidemics, which is why the United States made Daszak's watchlist for countries that are likely to be home to emerging infectious diseases. Combined with the overuse of antibiotics, tightly penned livestock such as chickens and cows can also play a role in jumpstarting outbreaks (as happened recently with both salmonella and E. coli threats).
A multidisciplinary movement called "One Health" has emerged as means of raising public awareness around threats of contagion and for developing ways of combating the problem. At its core, the movement seeks more recognition of the connections between the health of the environment, animals and human beings.
The movement's ecologists, veterinarians and doctors focus on a range of public health risks that stretch across their respective disciplines, including food- and water-borne diseases as well as other infections that are zoonotic (meaning they originate in animals before jumping to humans).
One Health advocates have plenty of work to do. Three of four newly emerging infectious diseases are zoonotic, and while there are roughly 2,000 known animal viruses, there are an estimated 1 million out there.
As a whole, infectious diseases kill some 15 million humans each year.
Ian Lipkin, a professor of epidemiology and pathology at Columbia University nicknamed the "microbe hunter," has come to know many of these diseases through his microscope. Lipkin helped McNamara prove that the same virus was behind both the bird and human outbreaks that became apparent at the Bronx Zoo in 1999.
"I'm convinced that was a bellwether event," Lipkin says of the West Nile virus outbreak. "A federal agency was embarrassed and vowed it would never happen again. One Health finally had legs."
At the end of "Contagion," a film on which Lipkin consulted, a short sequence of clips acts as a prequel to a One Health nightmare scenario: A bulldozer clears a patch of trees for a new piggery, into which a displaced and diseased bat drops a chunk of banana, which is gobbled by a pig that later lands in the hands of a chef.
"This is a classic example of an emerging infectious disease," says Lipkin. "The chef doesn't wash his hands, infects Gwyneth Paltrow, and we go from there," with a global pandemic soon following.
'VIRUS MIXING VESSELS'
The fictitious MEV-1 virus of "Contagion" was modeled after the real-life Nipah virus, which first swept through Malaysia's pig farms in 1998 and '99. Bats infected pigs, farmers got sick and millions of swine were slaughtered.
In fact, most of the biological factors that triggered the movie's pandemic have already happened, scientists say. The only element that remains fiction is the "incredible transmission among people," according to Rick Ostfeld, a disease ecologist at the Cary Institute of Ecosystem Studies in New York, who added that this last step is "not beyond the realm of possibility."
Hughes, the Emory professor, agrees.
"We've been relatively lucky that bird flu does not easily transfer from person to person," he notes. "But with an opportunistic mutation or two, an avian virus could be more easily transmitted to humans and then between humans."
A select group of animals pose the greatest threats of passing on a disease to humans, including one that could become contagious. These creatures -- whether wild, domestic or livestock -- tend to be those close to us, both in terms of physical proximity and genetics.
"The closer a species is related to us, the greater the chance that a pathogen it carries can infect us," says the EcoHealth Alliance's Daszak. "You're not going to die from a lizard virus, but you could from a mammalian virus."
Common culprits include ubiquitous rodents, backyard birds and primates, the latter blamed for the introduction of HIV. Bats pose yet another threat.
"Bats are the stuff Hollywood movies are made of," says Jennifer McQuiston, an epidemiologist at the CDC in Atlanta. "The fact that they can fly and migrate across great distances might mean they are exposed to more things that they can then bring back to naïve populations."
By destroying bat habitats, humans effectively encourage the winged mammals to search for surrogate sources of food –- such as fruit orchards -– that are located closer to where large clusters of people live. Bats are an effective carrier for Nipah because they don't suffer ill effects from the disease.
"A bat with Nipah doesn’t look ill at all," says Daszak. "But the virus is 70 percent lethal to people."
Pigs, like people, are highly susceptible to Nipah. These next links in the chain of transmission tend to live in close relation both to each other and to humans, making them prone to propagating and passing on the pathogen.
The close similarities between pig and human digestive and organ systems make them even more likely to bring disease. "Pigs are physiologically more similar to humans than many of us would like to admit," Lipkin says.
Within a pig, the virus can exchange genetic material with other native viruses, resulting in an amplified and human-ready pathogen.
In "Contagion," as Jennifer Ehly's character suggests to Laurence Fishburne's, it all started when "the wrong pig met up with the wrong bat."
FEVER FACTORS
In one recent outbreak, researchers found the same strain of E. coli in humans, pigs and spinach fields. "The same fingerprint was also in the manure that washed into the fields from cows on top of the hills," says Lonnie King, dean of The Ohio State University College of Veterinary Medicine. "If you look at it through the lens of animal health, it makes sense."
There's also an ecological lens. A hydrologist suggested that flooding may have mixed the surface water with groundwater, contaminating the irrigation systems. Sure enough, King said, the water systems were found to carry the organism.
"If you don't see these three entities together, then you don't understand the total outbreak," King notes. "You've got to move upstream and look at the environmental conditions and animal conditions, too."
Human odds of getting new infections also often jump with the introduction of non-native species to an existing ecosystem. This can be accidental, such as a sea creature hitching a ride on a boat, or it can be intentional, as witnessed through the far-flung global wildlife trade. A rodent trapped in the wilds of Africa and brought into the U.S. led to the emergence of monkeypox, for example, while monkeys themselves are another notorious purveyor of pathogen pollution.
On a macro level, climate change can influence the movement of animals from one habitat to another, creating novel interactions with other species, including humans. Even slight changes in temperature can affect reproductive cycles of disease vectors such as mosquitoes and ticks. Heat waves, droughts, floods and other extreme weather events have been linked to increased infectious disease outbreaks and, as a new report published this month reinforced, to global warming.
Many diseases emerge or reemerge as a result of multiple factors. The resurgence of malaria, for instance, is driven in part by climate change, human development and the overuse of pesticides.
A similar collection of unfortunate inputs could explain the dynamics of the bird flu, a disease that appears to be threatening to reemerge after a couple quiet years. The migratory pathways and movement patterns of wild waterfowl, which can be influenced by long-term climate change, are what "keeps the flu chugging along," said Ostfeld. Temporary limitations on standing water, such as drought, and permanent limits, like human development, forces more birds to fewer water sources, increasing the chance of contact and viral transmission.
A PATHOGENIC ARMS RACE
Tackling diseases from such a wide range of angles may sound novel, but the core concept behind the One Health movement is time-tested.
"Some of the greatest discoveries have been made at the interface of human and animal health," says Laura Kahn, a research scholar at the Woodrow Wilson School of Public and International Affairs at Princeton University. In the 1800s, for example, the chemist Louis Pasteur discovered the vaccine for chicken cholera, a disease that also infected many poultry farmers.
"The One Health idea was more apparent and accepted 100 or 150 years ago than it is now," says King, the Ohio State University veterinary college dean.
In the 1960s, many experts including the U.S. Surgeon General declared victory over infectious disease. Our new arsenal of antibiotics, vaccines, pesticides and water chlorination, they suggested, were vanquishing diseases such as whooping cough, polio, tuberculosis and malaria -- particularly in developed countries.
Their optimism proved premature.
Subsequent decades have brought the identification of Lyme disease, emergence of HIV and resurgence of tuberculosis -- including multi-drug resistant strains.
"There are many, many examples," of new diseases replacing those the industrialized world believes it has vanquished, or old diseases returning with a vengeance, says Hughes. "If you haven't learned to expect the unexpected, you haven’t been paying attention."
In addition to an ongoing arms race between pathogens and people, those trained to combat various aspects of the problem -- doctors and veterinarians, as well as environmental scientists -- have also grown increasingly specialized. Which is to say, they have grown apart.
"Physicians and veterinarians were not talking to each other, public health and agriculture folks were not talking to each other," says Kahn. That meant, she says, that it became easy to overlook links between fields.
A heart condition in tamarin monkeys, for example, was discovered decades before the same problem was identified in humans. "And no one spends a penny figuring out why it appears that sharks rarely get cancer," Kahn says.
Barriers between disciplines remain high, says McNamara, the former Bronx Zoo pathologist, partly because funding for research is highly prescribed, meaning that even in cases where a multidisciplinary team is ready to work together, it can be difficult to determine who is allowed to work on what and with whose funding.
Animal doctors generally get the short end of the funding stick.
More acutely, lingering professional schisms predisposes officials to be reactive to infectious diseases rather than getting out in front of the threat more proactively.
"Our health system is so tied into treating diseases and health care delivery, we lose sight of prevention," King notes.
Indeed, the public health system usually only springs into action after illnesses emerge.
"Once humans get sick, we start paying attention and taking action," says Kahn. "But the same disease had probably been in animals for a long time."
Referring to the West Nile virus outbreak that surfaced at the Bronx Zoo, Kahn points out that “no one was interested in listening to [McNamara] because she was a vet.”
Things have changed since 1999, but progress has been slow. Not until 2007 did the American Medical Association adopt a policy formally advocating closer ties between human and veterinary medicine.
That same year, however, the CDC opened the National Center for Zoonotic, Vector-Borne, and Enteric Disease. King, now of Ohio State, was the center’s first director and soon launched an office that he specifically designated as One Health.
"We brought together ecologists, physicians, veterinarians," he says. "The whole idea of One Health really started to take hold."
Still, a 2009 report by The Institute of Medicine and the National Research Council concluded that the authors were "unable to find a single example of a well-functioning, integrated zoonotic disease surveillance system across the human and animal health sectors."
"You don’t snap your fingers and it happens," King concedes. "It takes a while."
Education is another battlefront for the One Health movement.
Tufts University now offers a masters program in conservation medicine, while the University of California, Davis, holds a seminar series for ecology, medical and veterinary students called "Frontiers in One Health." The University of Florida graduated their first joint Doctor of Veterinary Medicine and Public Health class this year.
Meanwhile, international collaborations are enhancing worldwide surveillance of human and animal diseases, and sharing strategies. This February, the first International One Health Congress met in Melbourne, Australia. Bruce Kaplan, a retired veterinarian in Florida and member of the conference’s scientific advisory committee, hopes to further the cause through the One Health Initiative, a collaborative effort he started with Kahn a few years ago. He runs the group's website, which he noted hosts visitors from over 100 different countries every day.
Among those nations is Nigeria. Like its neighboring countries, Nigeria's infectious disease concerns range from the bird flu and rabies to Lassa fever, HIV, brucellosis and tuberculosis.
A OneHealthNigeria Google group led by Tayo Babalobi, a Nigerian veterinary epidemiologist, aims to serve as a platform for communication between medical, veterinary, laboratory and environmental scientists. Babalobi says Nigeria also has the world's first epidemiology program with a veterinary tract, which he says other African countries have expressed interest in emulating. Further, Nigeria is currently working to create a version of a One Health-centered CDC.
"We're seeing more adaptation of One Health in the developing world," says King, the Ohio State professor. "It makes sense. In these countries, animals and people are closely associated and you don't have to jump over the barriers of specialized medicine."
Rising fears over the use of biological weapons have garnered One Health greater attention within the U.S. defense community. Kahn, the Princeton professor, shifted her focus toward animal health after taking a course on weapons of mass destruction shortly after 9/11 and the 2001 anthrax attacks frightened the country. During the course, she learned the great majority of viral weapons are zoonotic.
It's no coincidence that zoonotic viruses don't need a lot of tweaking in the lab. As Laurence Fishburne's "Contagion" character says: "Someone doesn’t have to weaponize the bird flu. The birds are doing that."
BEYOND A VACCINE
Around the time the West Nile virus first emerged in the United States, McQuiston, a veterinarian by training, joined the CDC’s Epidemiology Intelligence Service. One of her key aims: controlling environmental factors enough to prevent people from getting sick in the first place.
“West Nile really emphasized that surveillance in animals can inform us about human risk,” she says.
Still, the CDC's primary responsibility is human health, leaving the surveying of wildlife disease to outside agencies like the Food and Drug Administration and federal and state departments of agriculture. Those agencies tend to focus on species of agricultural, hunting, fishing or conservation importance, according to McNamara.
As a result, she said, animals that come into close contact with people -- crows, pigeons, squirrels, pets and zoo animals -- escape such surveillance.
“The next infectious disease could emerge in a dog or a cat, or maybe some exotic species housed at a zoo,” McNamara says. “But a vet does not have the ability to pick up phone and call public health to get samples tested. They fall between the cracks. They are so common they are ignored.”
Zoos, she said, can help seal such cracks, as she saw in 1999. While the Bronx Zoo's flamingos, magpies and ducks fell ill, the chickens in the neighboring children's zoo remained healthy. This left all of the known poultry diseases unlikely to be responsible. Similarly, the emus were spared. Because emus are known to be sensitive to eastern equine encephalitis, they helped rule out that disease.
With funding from the CDC, McNamara has since helped establish a national disease surveillance system across more than 100 zoos and other institutions. "They have the unique advantage of having the entire animal kingdom to look across," she says.
Other scientific advancements have helped speed the identification of pathogens. The CDC now uses a device known as the Personal Genome Machine, which helped to identify the source of the E. coli outbreak in Germany earlier this year.
"If a person gets sick, we can rapidly test the pathogen in the person and then continue testing to make linkages and trace it back to its origin," says Greg Lucier, chairman and CEO of Life Technologies, which makes the PGM. He said the device could also help track the mutation of globe-traveling infections like the bird flu.
But the Cary Institute's Ostfeld and other experts urge broadening public-health strategies beyond vaccination and treatment.
"As long as our focus is exclusively on the ever-faster development of vaccines, we will be missing an opportunity to understand the principles of emergence that will help us anticipate when and where new emergence events will occur," Ostfeld says, adding that he was disappointed that ecological factors were barely covered in "Contagion."
"Ecological principles at the very least could help us target where surveillance can happen. We can't do it everywhere -- budgets are disappearing," he adds. "And if the ultimate solution is vaccination, the sooner we can to anticipate a species jump, the quicker we'd be able to act."
There is precedent for anticipatory action. Public officials usually deploy preparation and prevention techniques when they ponder natural disasters and terrorist attacks.
"We often know where earthquakes are likely to happen," Daszak notes. "So when building a block of apartments in one of these hot zones, we have incentive to build them with good foundations and proper structures so that they don't fall over."
While similar approaches should hold for environment-level safeguards from infectious disease, they simply don't yet. Just as Americans are not going to stop building houses in San Francisco, Daszak says, humans are unlikely to stop building roads through forests. "But we should aim to do it in a way that cuts down on the risks," he observes, proposing the prior identification of species and pathogens that might be affected and then responding accordingly.
As One Health continues to grow, Daszak predicts a shift from reactionary to proactive and precautionary within the next several decades.
"My dream is for us to stop a disease before any humans die. That's not going to happen tomorrow, but I think we're on track for that within next 20 to 40 years," he says. "Stopping a pandemic boils down to stopping the underlying causes. It's all about the environment, animals and humans."
"As 'Contagion' did beautifully show," says Ostfeld, "we don't have a moment to spare."
CORRECTION: In an earlier version of this article, a source misspoke about the prevalence of cancer in sharks. The source has since clarified her remarks. The article also erroneously named the university Dr. Lonnie King works at on a subsequent reference. He is the dean of the College of Veterinary Medicine at Ohio State.