The NIEHS, one of 21 institutes under the National Institutes of Health and the only one outside Bethesda, Md., had planned the roundtable discussion in July, because support for research is under fundamental review. But then the date coincided with the debate that a month ago was raging in Congress over raising the national debt ceiling.

David Price

For roundtable member David Price, a Democratic Congressman who has represented North Carolina’s Research Triangle since 1987, the debt ceiling debate signaled the sentiment shift in Washington, D.C. that also affects research funding.

“There’s nothing in the world that comes close to the NIH’s 100-year history, though other countries aspire,” Price said, talking about the role the NIH have played in supporting health-related research at universities and institutes nationwide with federal tax dollars.

Federal funding for research in disciplines from medicine to engineering has been the foundation onto which Research Triangle Park and its more than 40,000 jobs were built over the past 50 years.

But, Price said, “things we might have taken for granted, parts of the RTP success story, may have to be redefined.”

In 2009, UNC-CH, Duke, NCSU and RTI spent about $2.5 billion on research, according to the latest figures from the National Science Foundation and RTI’s 2009 annual report. Federal tax dollars made up more than two-thirds of the money spent.

The expenditures represented nearly 2.9 percent of the Research Triangle’s gross product that year. In 2009, the metropolitan areas surrounding Raleigh and Durham generated services and goods worth about $86.9 billion, according to figures of the U.S. Bureau of Economic Analysis.

Sponsored research is a formidable economic engine in the Research Triangle, paying salaries and creating jobs when startup companies are formed around technologies that were developed at area universities or research institutes. (More on sponsored research in the Research Triangle here and here.)

Linda Birnbaum

NIEHS injects about $200 million in federal tax dollars into the local economy per year, said Linda Birnbaum, NIEHS director and member of the roundtable discussion. About 1,400 employees work on the sprawling NIEHS campus in RTP.

“We’re really making an impact, not only economically, but scientifically,” Birnbaum said.

As proof, NIEHS had invited researchers from RTI, NCSU, UNC-CH and Duke to participate in the roundtable discussion. NIEHS has awarded grants to researchers at the three universities anchoring RTP and the research institute that started operations shortly after RTP was established in 1958.

Dr. John Hollingsworth, an associate professor of medicine at Duke, receives funding from the NIEHS to study whether environmental pollutants such as diesel exhaust and ozone cause genetic changes that affect how the immune system works.

His research is tracking the interaction of genetic and environmental factors behind inflammatory diseases such as asthma, especially during vulnerable periods like pregnancy. About 8 percent of the U.S. population suffers from asthma, Hollingsworth said, and his research could lead to new, innovative therapies.

Heather Patisaul, an assistant biology professor at NCSU, studies the effects of hormone-like substances on the developing brain. Among the environmental estrogens she’s tracking are genistein, which is in soy-based foods including soy baby formula, and bisphenol A, a chemical that is in metal food can linings and many plastic containers.

Genistein and BPA are suspected to impair fertility and trigger early puberty in girls.

Charle Rhodes shows off the sensor RTI researchers developed to test air quality.

At RTI, researcher have received NIEHS grants to study air quality inside and outside of homes and diseases associated with poor air quality, said Charles Rhodes, a senior fellow at RTI.

Rhodes brought a sensor that RTI developed to run the air quality tests. Similar sensors will be used in a study that is scheduled to start next year in areas devastated by hurricane Katrina six years ago. The sensors will measure the air quality in trailers the Federal Emergency Management Agency provided residents whom Katrina rendered homeless. The trailers have been called “toxic tin cans,” for high formaldehyde levels in the air inside and health problems that have plagued many who have lived in the temporary housing.

UNC has worked with the NIEHS for a long time, training more than 500 researchers, looking for ways to determine susceptibility to environmental diseases, tracking how carcinogens and toxicants make people sick and how environmental toxins interact with human genes.

In the past decade, UNC has received about $112 million in research funding from the NIEHS, said James Swenberg, a UNC professor in environmental sciences and engineering.

Swenberg said he’s been trekking to Washington for 25 years to talk to federal lawmakers and lobby for research funding. In the past, lawmakers were generally eager to learn regardless of their politics.

“Research had never been a partisan issue,” he said. “It’s not going to be the same this time around. That’s really sad.

Republicans, especially in the House, and candidates running for President in next year’s election are “catering to extreme antigovernment views,” Price said. “We have to leave no doubt, that we’re good stewards of our tax dollars and that [research funding] is not some academic pork barrel.”

Joan Roberts

Regardless of how many birthday cards, T-shirts and magazines declare that 50 is the new 30, the organs in our bodies start showing their age after 40. One of the first organs to do so is the eye, said Joan Roberts, a visiting scientist at the National Institute of Environmental Health Sciences in Research Triangle Park.

Presbyopia is what we notice – the eye’s lens loses elasticity, which makes it harder to focus on nearby objects and requires us to wear reading glasses. The chemical changes we don’t notice – at least not right away.

Between 40 and 50, the amount of protective antioxidants in our bodies decreases. That makes the eyes particularly vulnerable to damage from light, because it compounds a chemical change in the production of protective pigments that starts at about the same time.

The result, nearly 40 percent of Americans develop cataracts by the time they are 65 or older, according to data of the Centers for Disease Control and Prevention.

Cataracts, or clouding of the lens, can be treated with surgery. But when this increased vulnerability to light damages the retina, cells die and macular degeneration develops. This age-related disorder, which causes tunnel vision around a blurred spot in the center, affects about 5.6 percent of Americans 65 or older, according to CDC data.

Cataracts and macular degeneration aren’t avoidable, Roberts said, but their onset can be delayed.

Roberts, a chemistry professor at Fordham University in New York City who for 15 years has done part of her research at NIEHS, has more than 25 years experience tracking the good and bad effects of light on the eye.

Ultraviolet radiation is largely responsible for the bad effects, as Roberts described in a 2009 research paper.

The cornea absorbs UV light with the most potential for damage. In adults, the lens absorbs the remainder of the UV light and only visible light reaches the retina. But the eye’s natural defenses start to break down after 40. The chemical changes in the pigments and the loss of antioxidants cause damage to the lens that adds up over time. Clear lenses get cloudy. Cataracts develop.

Drugs, such as the antibiotics Cipro and tetracycline, and medicinal herbs such as St. John’s Wort, can accelerate the lens damage. So can light reflecting off of sand and snow.

Roberts, who said, “It’s my job to turn that 70 into 100,” had several suggestions how to delay the onset of cataracts: Antioxidant boosts through nutrition. Fruit and vegetables high in vitamin E and lutein and green tea were high on her list. Wraparound sunglasses protect on the beach and in the mountains.

Macular degeneration can develop following UV damage to the retina at a very young age or following prolonged damage by visible light called short blue visible light. Age-related changes in the eye’s pigments after the age of about 50 can promote such prolonged damage.

Roberts’ suggestion to delay age-related macular degeneration are Eagle Eye sunglasses, which were developed by NASA and designed for astronauts to block short blue visible light.

Irva Hertz-Picciotto

Irva Hertz-Picciotto is a slight woman stepping squarely into a brawl: the controversy over rising autism rates.

That the rates have been rising is undisputed. In the 1980s, about 6 of 10,000 were believed to have an autistic disorder, according to a 2007 paper. Today, autism spectrum disorders affect about 40 in 10,000. That’s a 600 percent increase, but opinions differ over what’s causing the increase.

Many researchers see forms of autism as predominantly inherited disorders whose diagnoses have dramatically increased, because parents have become more aware of telltale signs and children get diagnosed earlier, more frequently and with less severe symptoms than 30 years ago.

Others like Hertz-Picciotto, a professor of public health sciences at the University of California at Davis, aren’t so sure genes are the only culprits. But lacking data, they have had little to go on beyond questioning inconsistencies. How, for example, can it be that one identical twin has an autistic disorder but the other doesn’t, even though they share the same genetic information?

Also, at least one-third of the increase in prevalence has not been explained by higher awareness and a broader definition of autistic disorders, Hertz-Picciotto said Monday during a presentation at the National Institutes of Environmental Health Sciences in Research Triangle Park.

Source: Centers for Disease Control and Prevention

Considering the rapid rise of not only autistic disorders, but also asthma, obesity, diabetes and attention deficit hyperactivity disorder among children, she wondered whether there is “possibly a common set of environmental exposures that provides a unifying explanation for increased incidences of these conditions in recent decades?”

She was fully aware posing the question might open her up to criticism. “This is a little bit of a hot-button issue,” she said.

How hot, she found out last year when she suggested researchers should look for environmental culprits responsible for the increase in the autism rate in California. Her comment was part of a press release UC Davis issued after the publication of an analysis she and UC Davis programmer Lora Delwiche wrote on the rise in autism and the role of age at diagnosis. (Criticism in response to the statement here and here.)

Hertz-Picciotto, who studied effects of environmental exposures during prenatal development while she taught at the University of North Carolina at Chapel Hill in the 1990s, has become well known for her autism research. As a member of the UC Davis MIND Institute, she has been involved in two groundbreaking autism studies known as the CHARGE study and the follow-up MARBLES study.

CHARGE, which stands for childhood autism risk from genetics and the environment, started enrollment in 2003 to fill some large knowledge gaps in autism research.

“We know something about genes, but not which ones are the important ones,” Hertz-Picciotto said. “We know very little about the environment.”

So far, the CHARGE study has produced the following clues:

• Mercury and polybrominated diphenyl ethers or PBDEs, which are used as flame retardants on drapes and furniture fabrics, don’t seem to elevate the risk, but some pesticides do. (The pesticide results have not been published yet.)
• Maternal nutrition seems to make some difference, especially prenatal folic acid. (Results have also not been published.)
• Air pollution, unplanned Cesarean deliveries, maternal diabetes, obesity and hypertension and maternal fevers may also increase the risk, but data collection is still under way.

Also, a study by other autism researchers suggested autism may be linked to maternal immune responses, such as inflammation and immune disorders. Up to 12 percent of the mothers of kids with autistic disorders produce specific antibodies to fetal brain antigens. Based on the immunological research results, Hertz-Picciotto suggested to investigate immunological toxins, not just neurotoxins.

The CHARGE and MARBLES studies are being conducted in California, a state with a rich epidemiological database of autistic disorder diagnoses. Researchers in Pennsylvania and Maryland participate in the CDC’s EARLI study, which follows 1,200 mothers of children with autism at the start of another pregnancy and documents the newborn child’s development through three years of age.

At UNC-CH, research involving fruit flies has advanced understanding of autism.

It’s much harder to prove it.

It may require data that’s not available or collaboration across scientific disciplines with very different views of the world, disciplines such as chemistry, urban planning and epidemiology, for example.

To overcome some of the hurdles, more than 80 researchers and politicians gathered this week at a two-day conference the Research Triangle Environmental Health Collaborative called in North Carolina’s Research Triangle Park.

Thomas Burke. (Photo by Will Kirk, Johns Hopkins University Gazette)

Among the speakers at the conference: Paul Anastas, the father of green chemistry, whom Pres. Barak Obama appointed assistant administrator of the U.S. Environmental Protection Agency’s Office of Research and Development; Thomas Burke, associate chair of the Johns Hopkins Bloomberg School of Public Health; and Hal Zenick, director of the EPA’s National Human Health and Environmental Effects Research Laboratory in RTP.

“The seeds are here,” Burke said, scanning the conference participants. “The right people are here in this group.”

The conference location reflected the concentration of environmental health research brainpower in RTP, home to the EPA’s main air pollution research and regulation center and the National Institute of Environmental Health Sciences. Also, RTI International has looked into environmental factors of diseases, particularly in poor countries, for nearly half of the 50 years the RTP-based research institute has existed.

The timing of the conference was also poignant. While the participants at the RTP conference worked on a roadmap to identify and abolish environmental disease triggers, researchers from the Children’s Hospital in Boston released results of a study that illustrated the hopes and frustrations of their colleagues in RTP.

One of the first of its kind, the study showed that air pollution in an area is a strong predictor for the prevalence of diabetes among people living in the area. The higher the exposure, the stronger the relationship.

Left, a map of diabetes prevalence. Right, a map of soot prevalence. (October issue of Diabetes Care)

The conclusion was based on data from the EPA, the Centers for Disease Control and Prevention and the U.S. Census. The researchers at Children’s Hospital Boston took county-by-county EPA data of what is called PM2.5, tiny particles and droplets that are the main components of haze, smoke and motor vehicle exhaust. They combined the PM2.5 data with CDC data of where people with adult-onset diabetes live. And then, they made sure the study outcome wasn’t skewed by other known risk factors such as obesity and ethnicity.

Even soot levels below EPA safety limits were linked to diabetes prevalence, according to the study.

What the study couldn’t prove was that the particles, which are small enough to reach the deepest regions of the lungs, caused diabetes. To do so, the researchers would have needed data they didn’t have, results from blood or urine tests, for example, to see whether people who were exposed to more particulates were also more likely to show precursors of diabetes, such as inflammation or insulin resistance.

These individual test results are frequently hard to come by, researchers at the RTP environmental health summit suggested. That’s why they recommended that North Carolina establish a biomonitoring program with blood and urine tests to measure individual exposures to key contaminants.

Other recommendations from conference participants included:

• Form research teams that from the beginning of a research project are made up of scientists from different disciplines to make sure data are generated following common goals.
• Crowdsource data, particularly in cases where very little information is available. Example: The interaction of lifestyles and foods in the worldwide obesity epidemic.
• Involve doctors, nurses and community advocates in environmental health research and training.

Read all recommendations from the conference here.

More coverage of the conference here.

Crossing Research Triangle Park on Interstate 40 or visiting Duke University, the University of North Carolina at Chapel Hill or N.C. State University provides little insight into what fuels one of the hottest U.S. research and development hubs.

Michael Walden

Sure, the Triangle was named the brainiest U.S. region and Raleigh the fastest growing metropolitan area last year. And the area’s vaunted labor pool continues to draw scientists and R&D companies from elsewhere, even though companies have closed shop or laid off employees in the past two years and the unemployment rate in the Triangle is nearly twice as high than before the economic downturn.

Mike Walden, an NCSU economist, doesn’t mince words when he assesses how important R&D is for the RTP area. “It’s one of our basic industries,” Walden said. “It’s one of the things that make us tick.”

But what sustains and boosts this industry that, it can be argued, flavors everything locally from schools to restaurants?

The credit usually goes to the three main research universities, Duke, UNC-CH and NCSU, and the hundreds of companies in and around RTP. But what specifically is it that they do to shape the RTP area? Is it the graduates they produce every year, the discoveries they spin off into local startup companies, or the money they spend on R&D?

Looks like the money spent on R&D is most important, according to a 2009 Federal Reserve Bank of New York staff report by Jaison R. Abel and Richard Deitz.

Nationwide, federal funds pay for a considerable amount of R&D to boost public knowledge and inform public policy. Especially universities and nonprofit institutes rely on research grants from the National Institutes of Health, including the National Institute of Environmental Health Sciences in RTP, and other branches, such as the Department of Energy and the Department of Defense.

Foundations, patient advocacy groups, wealthy individuals and large companies also pitch in.

R&D spending in the Triangle

In 2008, the Triangle’s three research universities and RTI International, an RTP-based research institute, spent about $2.34 billion on R&D, according to a survey by the National Science Foundation and RTI’s annual report.

That’s about double their 2001 R&D spending. The steep increase reflects a doubling of the NIH budget in the first half of the decade and emphasizes the importance of the life sciences in the area.

The $2.34 billion – the actual investment in R&D would be slightly higher if hard-to-come-by corporate R&D expenditures were included – represented about 2.7 percent of the area’s gross product that year. In 2008, the metropolitan areas surrounding Raleigh and Durham generated services and goods worth about $86 billion, according to figures by the U.S. Bureau of Economic Analysis.

The same year, retail contributed about 4.5 percent of the area’s gross product, BEA figures show.

Economists have long known about universities long reach locally, Abel and Deitz, the two staffers at the Federal Reserve Bank of New York, pointed out in their report. Universities generate the innovation and the educated labor force needed to drive a knowledge-based economy.

What Abel and Deitz added was the empirical evidence that degree generation was less important than R&D spending and the spillover from lots of research, meaning start-up companies that capture the most innovative technologies coming out of universities.

The two Federal Reserve staffers concluded that “research-intensive metropolitan areas tend to have larger shares of the most highly skilled occupations (e.g., those in the categories life, physical and social sciences; legal; computer and math; architecture and engineering; business and financial operations) and smaller shares of the lower skilled occupations (e.g., those in food preparation and serving; production).”

Cryptococcus gattii

In Africa, South America, Southeast Asia and Australia, crytococcus gattii infects eucalyptus trees and bothers people with compromised immune systems, such as HIV/AIDS patients and organ transplant recipients, who inhale its spores. But the strain that was first documented on Vancouver Island, Canada, a decade ago and has now spread to Seattle and Portland causes chest pain, fever, shortness of breath and weight loss in otherwise healthy people and has killed at least six of them.

In February 2007, the first North Carolina case, an otherwise healthy man, was treated at Duke University Medical Center, the Duke researchers reported in PLoS One. In a paper they published a week ago in PLoS Pathogen, the researchers wrote that the cryptococcus gattii strain in the Pacific Northwest was new, much more virulent and favored mammals.

The second Duke paper followed on the heels of a report on human health and climate change that was authored by a group of researchers from several federal agencies. Lead author of the report was Christopher J. Portier, the head of the environmental systems biology group at the National Institute of Environmental Health Sciences in Research Triangle Park.

“The purpose of this paper is to identify research critical for understanding the impact of climate change on human health so that we can both mitigate and adapt to the environmental effects of climate change in the healthiest and most effective way,” the report from the Interagency Working Group on Climate Change and Health read.

Filling research gaps in new diseases and well-known diseases that are coming back because of altered growing seasons, more rain in some areas and droughts in others, more violent storms and rising temperatures has been on researchers’ minds for years.

In the past decades, they have identified 30 new diseases, including hepatitis C, avian flu, HIV/AIDS and severe acute respiratory syndrome, or SARS, according to a 2004 report in Nature Medicine. Environmental changes are among the reasons for the emerging diseases. But researchers have also tracked a resurgence of previously documented diseases in new geographic areas, among them tuberculosis and cholera.

The report from the federal interagency working group zeroed in on the following research areas:

• More mold, dust, pollen and air pollution are likely to increase the prevalence of airway diseases such as asthma and respiratory allergies, which already affect about 50 million Americans.
• More information is needed on how climate change affects exposure to toxins and chemicals that might boost cancers, with about 500,000 deaths per year the second leading cause of death in the U.S.
• Heat waves and rising global temperatures could increase the number of heat-related illness and death. The 2003 heat wave in Europe, for example, caused about 35,000 deaths.
• Some birth defects linked to environmental causes have been steadily increasing.
• Exposure to biotoxins from ever more frequent, harmful algal blooms and chemicals from new batteries and compact fluorescent light bulbs could boost neurological and waterborne diseases.
• By 2050, about 200 million people are expected to be displaced by the effects of climate change. The population relocation and the changes in temperatures could cause a resurgence of diseases caused by insects, such as malaria and yellow fever, which were once rampant in parts of the U.S.

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