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By Marilyn Werber Serafini, National Journal
© National Journal Group Inc.
Friday, July 6, 2007

Scientists at the drug-making giant Novartis weren't consciously responding to global warming four years ago when they began pumping millions of dollars into the search for a treatment for dengue fever, a sometimes deadly tropical disease so painful that it's also known as "breakbone" fever. They knew only that reported dengue cases were on the rise globally -- nearly doubling in less than a decade, to 900,000 a year -- and that no vaccine existed to prevent it and no medicine to treat it.

Native to Southeast Asia but growing most rapidly in Central America and the Caribbean, dengue is spread by the ever-pesky mosquito and in humans causes severe joint pain, high fever, headaches, vomiting, and rashes. Hemorrhagic dengue -- the most dangerous form -- breaks down blood vessels, causing internal bleeding that can be fatal.

To focus on dengue, malaria, and other "neglected" illnesses, Novartis founded the Institute for Tropical Diseases, located in Singapore. "When we first started with dengue, [climate change] wasn't in our thoughts at all," says Paul Herrling, head of corporate research at Novartis International. Researchers assumed that the explosion of dengue cases was somehow related to increases in travel and population density or to the decline in the use of the potent but environmentally hazardous pesticide DDT, Herrling recalls. But, he says, he soon began fretting that global warming was an important culprit -- and that its fueling of the dengue epidemic might be just a tiny fraction of the threat it posed to human health.

In February, a draft report from the United Nations' Intergovernmental Panel on Climate Change confirmed Herrling's suspicion. The panel found an alarming link between global warming and four potentially lethal problems. In 2000, climate change killed 150,000 people, the panel estimated. Scientists consider that figure conservative, however, because it's limited to global warming's impact on malaria; diarrheal diseases; floods and landslides; and malnutrition. Indeed, scientists forecast climate-related increases in allergies, asthma, skin cancer, dengue, Lyme disease, heatstroke, sleeping sickness, and a host of other ailments.

Looking ahead, the U.N. panel predicted that the world's poorest and sickest regions will suffer the most from global warming. It forecast "large changes" in the risk of malaria in countries bordering already infected areas and warned that as many as 6 billion people worldwide could be at risk for dengue by 2085.

Despite these warnings, many pharmaceutical companies say they've given little thought to how global warming should affect their long-term plans for developing medicines and vaccines. Novartis is an exception: Most drugmakers are focusing on global warming only as it relates to cleaning up their own manufacturing practices -- by reducing carbon dioxide emissions, for example.

Some company representatives say that it's too early to respond, because the health effects of global warming aren't fully understood. And the federal government is just beginning to try to figure out the potential health effects. "We're trying to determine what our role should be," said Michael McGeehin, division director of the National Center for Environmental Health, which is part of the Centers for Disease Control and Prevention. As the CDC begins to grapple with the possible consequences of climate change, it is preparing a series of workshops on heat waves, vector-borne diseases (those spread by mosquitoes, ticks, fleas, and the like), waterborne diseases, and health communications, and McGeehin says he wants to move quickly. Meanwhile, the National Institutes of Health, which, like the CDC, is part of the Health and Human Services Department, is examining the effects of exposure to ultraviolet rays, air pollution, and vector- and waterborne diseases.

Yet even if scientists were further along in identifying all of the potential health consequences of global warming, they still wouldn't know how to accurately predict which ones are most likely to merit drug companies' attention and resources. "There are so many variables that it would be ill-advised to be thinking that we know which specific diseases in each specific area [will] increase by a specific amount and [how much to] ramp up drug production and preparedness," says Jonathan Patz, a professor of environmental studies and population health sciences at the University of Wisconsin (Madison) and a former co-chairman of the health expert panel of the U.S. National Assessment on Climate Change. "It's not feasible from a business perspective because we don't know whether [the drugs] would be used."

And it's not as if drugmakers are twiddling their thumbs: "There are so many existing unmet health needs," noted Ian Spatz, Merck's vice president of public policy. "The focus is very much on those, and not on other potentially small changes in how common [certain] illnesses are over a very long period of time. There's plenty facing us right now."

Industry critics disagree, saying that the question of profit is too often the deciding factor in drugmakers' planning. One of the biggest health consequences of global warming is likely to be that it expands the range of mosquito-borne illnesses, now largely confined to poor tropical countries with little money to pay for high-priced pharmaceuticals.

What's more, critics say, the pharmaceutical industry seems more interested in chronic diseases -- because their accompanying need for daily medication produces a steady income stream -- than in infectious diseases that a few doses might knock out.

A Growing Peril
According to the U.N. report, the health effects of climate change will increase gradually over the next few decades -- and by midcentury have a noticeably stronger impact than they have now.

Perhaps the chief causes of worry are the diseases that mosquitoes, ticks, and tsetse flies carry, such as dengue, malaria, Lyme disease, West Nile virus, tick-borne encephalitis, and sleeping sickness. Already, as temperatures have risen over the past 20 years, dengue and malaria have followed mosquitoes into new geographic areas and higher elevations.

Malaria is one of the most climate-sensitive diseases, according to Patz. It kills more than 2 million people every year, most of them African children. Although treatment for malaria exists, drug-resistant strains continue to emerge, so new medications are needed.

Parts of South America, meanwhile, are reporting widespread outbreaks of dengue, which the U.N. panel called "the world's most important viral vector-borne disease." According to the panel, "While high rainfall or high temperatures can lead to an increase in transmission, studies have shown that drought also can be a cause if household water storage increases the number of suitable mosquito-breeding sites." Already, one-third of the world's population lives in places where dengue is a danger because of the climate.

The U.N. report forecasts that waterborne diarrheal diseases could rise 5 percent in poor regions by 2020. That's because warmer temperatures could mean more floods and droughts, and more runoff of contaminated water into clean water. A recent study found that as the average daily temperature rose in Peru in 1997-98 because of an El Nino, so did the number of children hospitalized because of serious diarrhea.

Global warming is also affecting vegetation. If you've noticed that your hay fever has started kicking in earlier and hanging around longer, it's because climate change has already lengthened the pollen season in North America and Europe, according to the U.N. report. For the mildly allergic, that has meant itchier eyes and more sneezing, but the problems may be much worse for asthma sufferers and those prone to other respiratory illnesses.

Lewis Ziska, a plant physiologist at the Agriculture Department's Agricultural Research Service, has studied the correlation between climate change and ragweed. For two years, he grew ragweed in rural areas and cities. Because cities have higher temperatures and levels of carbon dioxide, Ziska thinks they resemble the world's environment in another 50 to 75 years.

Ziska's city ragweed grew faster and bigger, flowered earlier, and produced more pollen than its country cousins. He expects some other allergenic plants, including tree and grass species, to behave similarly. And he is starting to examine the impact of climate change on mold and dust mites, both of which thrive in warm, moist places.

Already, people are twice as likely to suffer from asthma and allergies as they did in the 1970s, according to Ziska. The U.N. report also cited studies forecasting a 68 percent increase in the number of ozone-alert days by 2050. High levels of ozone make it hazardous for people with respiratory problems to be outdoors.

Some early evidence shows that poison ivy and other poisonous plants are becoming more potent as carbon dioxide levels rise, while the caffeine and nicotine in plants may be losing some of their zing, Ziska said. At the same time, rice, wheat, and some other edible plants might suffer a decline in protein, omega-3 fatty acids, or antioxidants, he added.

If climate shifts change the potency of medicinal plants, pharmaceutical companies and herbal suppliers around the globe could find it more difficult to gauge the power of plants that they've long relied upon. The World Health Organization estimates that 3.5 billion people rely on the medicinal powers of actual plants. "This is more of an issue in developing countries," Ziska said. "But if you go to an apothecary, and they say to take 'x' amount of a leaf and it will cure your diarrhea -- if the concentration [of the plant's medicinal property] is changing [because of global warming], how will it affect how [they] prescribe?"

Ziska cited a climate-change study showing that the concentration of the active medicinal ingredient in the plant known as Saint John's wort will increase. Saint John's wort is a common herbal treatment for depression and anxiety. Native Americans have also used the plant for generations as an anti-inflammatory and antiseptic.

About 10 to 15 percent of pharmaceuticals, meanwhile, are derived from plants, Ziska said. The only effective treatment for malaria, a major global-warming threat, comes from a Chinese plant.

The U.S. Connection
Just because global warming is likely to expand the range of some illnesses and make others more serious, that doesn't necessarily mean that prodding pharmaceutical companies to pump out new and improved drugs is the best response, according to Darryl Zeldin, a senior investigator with the National Institute of Environmental Health Sciences. He advocates a different tack: Why not try to prevent malaria with bedding nets and insecticides? Keep allergy sufferers indoors at the height of pollen season, and use dehumidifiers to prevent mold? "We would much rather focus our research on understanding environmental triggers and on ways of reducing exposures in the environment," Zeldin said. "If you have asthma, is it better to take drugs that mask symptoms?"

Patz suggests stepping up efforts to protect drinking water from contamination during heavy rains and even floods, and establishing early-warning and early-response systems to cope with heat waves.

But whatever the pharmaceutical effort, it must begin soon, said Christopher Earl, president of BIO Ventures for Global Health, a nonprofit that encourages private-sector involvement in public health. "It takes [at least] 10 to 15 years from the gleam in your eye [to getting a drug to market]. If you're trying to plan ahead, and you want to bring climate change into the decision-making, you need to have some sort of predictive models that are reasonably reliable. And currently, the U.S. government has done a poor job of letting the pharmaceutical industry know that this is important, and what they need."

Nevertheless, Novartis is forging ahead. The company is hoping to begin clinical trials on a dengue treatment next year and to have a treatment for it in pharmacies by 2012. The company's Institute for Tropical Diseases is spending $15 million a year on developing drugs for dengue, malaria, and tuberculosis. (TB has no known connection to climate change.)

"We can't do everything alone," says Herrling, who is reaching out to other drug companies to figure out a way for them to collaborate without running afoul of antitrust laws. Already, he said, GlaxoSmithKline and Sanofi-Aventis are beginning to focus on these issues.

Sanofi has partnered with the Drugs for Neglected Diseases Initiative, an international collaboration between government and businesses. The company is working on new treatments for drug-resistant malaria, according to Robert Sebbag, its vice president of access to medicine.

Eventually, other pharmaceutical companies will take note, Earl predicts. "Let's say, as a result of climate change, the dispersal of infection-carrying mosquitoes changes. They go into territories where they haven't been before. Talk about dengue marching into Texas.... If dengue starts to appear more in paying markets, as opposed to poor countries where people can't pay, we may see more interest in developing antivirals or vaccines to treat dengue." Already, said Sanofi's Sebbag, dengue is on Caribbean islands, creating the risk of carrier mosquitoes "coming into Key West and, step by step, arriving in [mainland] Florida and transmitting dengue."

According to Patz, regardless of whether global warming sickens Americans by bringing dengue to the nation's shores or making life miserable for allergy sufferers, the U.S. has a moral obligation to take the health consequences of climate change seriously: "Poor countries in Africa or Latin America are barely contributing to the problem of global warming, because they're not driving cars around. This is a travesty. [The United States is] 5 percent of the world's population emitting 25 percent of the world's greenhouse gases. Our energy policies are [exporting] diseases around the world."