Upcoming Event

Public Health Cafe

Nanotechnology & Nanotoxicology                  Save the date:
with Center Director Terry Kavanagh               Tuesday, May 13th, 7-8:30 pm
& PhD student Megan Cartwright                    Chaco Canyon Cafe, West Seattle

Event Highlight: CEEH Outreach at UW Science and Engineering Fest in Yakima

UW Freshman Jose Lopez helped at the Pesticides & Health table hosted by the Center's Outreach Group 
Along with other UW programs, the Center's Community Outreach and Ethics Core (COEC) hosted a table at the UW Genome Sciences Education Outreach (GSEO) annual Science and Engineering Festival in Yakima on March 25-26. The audience was junior high and high school students and the community.

The theme of our display was Pesticides and Health: Ethical Implications for Genetic Testing in the Workplace. We offered this verbal spiel, in English and Spanish:

  • Pesticides are chemicals that kill insects and weeds. Do you think something intended to kill insects are good for people? (Our visitors thought not).
  • Gene-environment interactions help explain why some people get sick from being exposed to toxic substances like pesticides, and others don't.
  • We all have a gene called PON1, for paraoxonase 1. The gene holds the recipe for an enzyme that's also called PON1. Because of small differences in the PON1 gene, different people make very different amounts of the PON1 enzyme.
  • The job of the PON1 enzyme is to break down foreign molecules in our bodies. PON1 breaks down organophosphate pesticides. 
  • People who have less PON1 enzyme have a higher risk of getting sick from being around pesticides because the pesticide stays in their body longer.
Visitors answered 4 ethical questions by dropping a colored stone in a graduated cylinder labeled Yes or No. The questions were:
  1. If you had a genetic variant that made you more likely to get sick from pesticides, would you want to know?
  2. Should genetic testing be required for employees who work with pesticides?
  3. If a worker has been tested for PON1 status, to measure if they are more likely than average to get sick from pesticides, should their employer be told the test result?
  4. Should family members who live with a farm worker, and those who live or go to school near farm fields, also be tested for PON1 status to find out if they are more likely to get sick from pesticides?
We offered our handout about PON1. We also have a fact sheet, Health Risks of Pesticides in Food.

The majority answered Yes to all questions. Nearly everyone answered Yes to Q1, wanting to know their own risk. More visitors answered No to each subsequent question. Students were more likely than adults to answer Yes, they would share genetic information with employers Adults were more hesitant, and some even debated the pros and cons out loud. Some feared workers would be discriminated against if test results were known. 

For Q4, a larger minority answered No, they didn't think family members should be tested. Some shrugged, perhaps feeling it didn't matter, or there was nothing they could do about it. One mother told of living in a home surrounded by orchards with a young child who had severe asthma. She asked the orchardist if he could let the family know when pesticide spraying would be done so they could take the child away. The orchardist was unable to tell her when the spraying would happen.

Among our visitors were farmworkers, orchardists, and student and adult community members who lived near orchards and fields. Everyone seemed to know that pesticides are dangerous. Several reported that personal protective equipment is highly regulated and used, which was good to hear.

Many visitors wanted to know how to protect themselves. We offered to stay inside during spraying; wash fruit and vegetables; eat organic produce if possible; eat green tea and blueberries--foods like these that are high in antioxidants can increase the activity of PON1.

Pesticides, health, and genetics were pertinent topics to bring to the agricultural Yakima Valley. It's valuable to go to communities with our Center research, both to share what we know and to listen and learn from them.

- Marilyn Hair

On Our Minds: Musings about Collaboration, Continued

Our Community Outreach & Ethics Core works to ensure that collaborations between researchers and community groups are mutually beneficial and transparent.  Photo © 2014 Clipart.com.

My recent leadership responsibility with the IFOPA has me thinking more directly about the role collaboration plays within our Center. Collaboration is a bit different in the Center for Ecogenetics and Environmental Health than for the rare disease community I described earlier. There are no pharmaceutical companies. There is no single disease population or organized patient group. Still, scientists engaged in basic research need participants for their studies. Basic scientists need clinicians to describe the disease phenotype. Researchers need informaticians to help ask the right questions. And findings need to be translated to the next phase of research to be included in policy and practice.

Let’s take one of those stakeholders: the general public. Why should they care about environmental health research? 

  • People get sick from environmental exposures. Anybody who has asthma, or whose children have asthma, has a stake in research about air pollution. People with a family history of cancer or heart disease have a stake in research related to those diseases. 
  • An emerging hazard may alarm the public, for example the meltdown of Japan’s Fukishima nuclear reactor in 2013. People on the west coast want to know if they are being exposed to radiation. Thankfully, tests indicate low radiation levels, but if results were otherwise, concerned citizens might ask to participate in research studies. In cases of industrial pollution or exposures from factories, citizens come to scientists asking for research. 
  • Potential participants might be interested in science, or simply be curious. Others are activists who like to be involved. Some sign up to get the monetary incentives. 

Public engagement professionals like us in the COEC can help educate the public about the importance of research and the need for participants. 

Once identified and recruited, researchers need to retain their participants. A few simple strategies can maintain participant interest. Hearing back about the study lets participants know their role is important and appreciated. Researchers can send results via newsletter updates or a summary of publications written for a general audience. 

In January, the Center sponsored the first meeting of our new CEEH Breakfast Club, a monthly gathering of Center members for an informal presentation and discussion. The topic was crowdfunding for science. Dick Beyer spoke about participating in the American Gut Project to have his microbiome sequenced. Dick displayed a placemat-size printout with his name in large letters and pie charts of the relative abundance of his microbes and how he compared to others. Not only did he participate, he paid $100 for the privilege, although scientists don’t claim to understand how the composition of our microbiome affects our health. 

Someone asked whether Dick would participate again. “Oh, yeah,” he responded.  “I'm really glad American Gut is doing this. But I mainly wanted to learn something about me.” Getting his results, even results that aren't closely tied to health, was worth not only participating but paying for it.  

It could be we need to think a bit more – and ask – about what we can get from and give back to participants. The answers might surprise us!

On Our Minds: Musings about Collaboration, A Case Study of Science in Action

In my outside-of work life, I am the mother of a child with a rare disease. I recently volunteered to chair the Board of Directors of the international patient group. My involvement with leading this group as it approaches a clinical trial has taught me a considerable amount about research-in-action and the importance of collaborative partnerships – two themes of high relevance to our Center.

The disease is an ultra-rare, catastrophic genetic condition called Fibrodysplasia Ossificans Progressiva (FOP). FOP causes bone to grow in skeletal muscles, creating a second skeleton that freezes joints and prevents movement. There are fewer than 900 known cases of FOP in the world.

Marilyn at a recent IFOPA meeting.
The patient group is the International FOP Association or IFOPA, founded in 1988. Medical research in FOP has increased dramatically since the patients organized, and what is understood about the condition has progressed greatly. The most important discovery so far happened in 2006 when researchers at the University of Pennsylvania identified the FOP gene. Since the gene discovery, attention from researchers and, recently, from pharmaceutical companies, has grown exponentially, and along with it, our need to navigate across stakeholder groups.

To collaborate is to work jointly on an activity to produce something or work towards a shared goal. The collaboration of patients, researchers, and pharmaceutical companies fits that definition, but it is not exactly a group project where everyone has the same goal. These stakeholders have different perspectives, and although they are all working on a treatment for FOP, their goals and motivations differ:

  • FOP patients want a treatment for their disease, and something to allow rehabilitation from damage already done. Patients are in a race against time because FOP is progressive. 
  • The patient group, the IFOPA, wants to encourage drug development by contributing natural history data to document the natural course of FOP, collecting patient data, and encouraging its members to participate in clinical trials. Data collected in one international registry and owned by the IFOPA would let the patient group control the data and share it with research and pharmaceutical stakeholders. 
  • Researchers want their work to lead to discovery: A gene, a disease mechanism, a drug candidate. Researchers need publications and grants. Since they compete with other researchers, they also want to protect their data, which can be an unfortunate barrier to collaboration. 
  • Pharmaceutical companies want a product. They want successful clinical trials, regulator approval, and a useful drug. In rare disease research, pharmaceuticals want a wider audience to buy the drug, to meet their ultimate goal of making a profit. The pharmaceutical companies working on FOP hope their drugs will also help non-genetic conditions of bone growth that comes up after hip and knee replacements, spinal cord injuries, stroke, atherosclerosis, closed head injuries, and heart valve replacement surgeries. 

Despite their different perspectives, we stakeholders need each other. Only through collaboration will we be able to reach the goal of finding a treatment for FOP.



Research Highlight: Exposure to Air Pollution Early in Life Could Lead to Heart and Lung Disease in Adulthood

Center investigators are exploring links between diesel exhaust exposure and several chronic diseases.

Our Center has been researching respiratory susceptibility since the Center was founded in 1995. For the first eight years, we focused primarily on air pollution and asthma. In 2003, we began to look at how environmental factors can increase the risk of other conditions, such as cardiopulmonary and cardiovascular diseases.

The public health impacts of cardiopulmonary and cardiovascular disease are huge. Atherosclerosis, the buildup of cholesterol and fats in the coronary arteries that supply blood to the heart, is the #1 killer of both men and women in the United States.1 In recent years, it has become clear that environmental factors play a major role in the risk of cardiovascular disease, and that these factors could potentially be modified to reduce risk. The Center’s Cardiovascular Toxicology Area of Research Emphasis (ARE) brings together several researchers who are working in this promising field.

Cardiovascular toxicology is the study of the adverse health effects of toxic chemicals on the heart or blood systems. An important component of cardiovascular toxicology is identifying the exact mechanisms by which chemicals cause harm to the body. Several CEEH investigators are exploring possible mechanisms using engineered animal models. For example, ongoing projects in the Cardiovascular Toxicology ARE explore the roles of genetic susceptibility and gene expression in an effort to understand precisely how ambient particulate matter can contribute to cardiovascular and pulmonary diseases. Particulate matter refers to the complex mixture of very small particles and liquid droplets present in air.

Dr. Michael Chin
One example of this research is a study of diesel engine exhaust exposure, epigenetic changes and heart failure in mice. The project began as a CEEH Pilot Project Award in 2013, led by Cardiovascular Toxicology ARE researcher and cardiologist Dr. Michael Chin. The Center funds four to six small pilot projects each year. Pilot project grants are designed to help investigators to obtain preliminary data that will be useful for competitive, full-scale grant applications. CEEH has awarded a total of 74 pilots since 1995, investing approximately $1.85 million to date in these small, innovative research projects.

Dr. Chin and his team, which included Chad Weldy, Yonggang Liu, Yi-Chi Chang, Ivan Medvedev, Julie R Fox, Timothy Larson, and Wei-Ming Chien, studied exposure to diesel exhaust (DE) because DE is the greatest source of traffic-related fine particulate air pollution. Exposure to DE has been shown to be associated with an increased risk of cardiovascular disease and death. However, little research has been done on the potential long-term effects of exposure to DE in the womb (in utero) and during early development. Dr. Chin and his team wanted to know if in utero and very early life exposures could increase susceptibility to heart disease later in life.

To explore this question, the research team exposed mice to either filtered air or DE only during in utero and early life development. The researchers found that when the mice exposed to DE were raised to adulthood, they were significantly more susceptible to heart failure. Following a surgery to induce heart failure, these mice showed greater enlargement of the heart, worse contractile function, extensive fibrosis (build up of scar tissue within the heart), and lung congestion. They also showed a change in the inflammatory response in the lung, suggesting that environmental challenges during these developmental windows may be important not just to the heart, but also to the lungs.

Dr. Chad Weldy enjoys a rare moment away from the lab.
The researchers concluded that exposure to diesel exhaust air pollution in utero and in early life increases susceptibility to heart failure in adult mice. These results suggest that the effects of air pollution on cardiovascular disease in humans may originate from very early life exposures.2

A more recent paper in PLoS ONE links in utero exposure to DE to weight gain and changes in blood pressure, as well as increased risk of heart failure.3

Dr. Chad Weldy, Senior Fellow within the Division of Cardiology and lead author, says: “This work expands our understanding of how environmental exposures during early life development contribute to disease. As we learn that in utero development is critical for setting adult health, we need to further investigate how common environmental exposures may adversely impact development and increase lifelong risk of disease. I hope to see this work continue as epidemiological studies, where we can determine if these effects we see in the lab are also occurring in human populations. These future studies may prove to be crucial for setting regulatory policy, reducing environmental exposures, and improving public health.”

References:
  1. http://www.nhlbi.nih.gov/health/health-topics/topics/atherosclerosis/atrisk.html.
  2. Weldy CS, Liu Y, Chang YC, Medvedev IO, Fox JR, Larson TV, Chien WM, Chin MT. In utero and early life exposure to diesel exhaust air pollution increases adult susceptibility to heart failure in mice. Particle and fibre toxicology. 2013;10(1):59. Epub 2013/11/28. doi: 10.1186/1743-8977-10-59. PubMed PMID: 24279743.
  3. Weldy CS, Liu Y, Liggitt HD, Chin MT (2014) In Utero Exposure to Diesel Exhaust Air Pollution Promotes Adverse Intrauterine Conditions, Resulting in Weight Gain, Altered Blood Pressure, and Increased Susceptibility to Heart Failure in Adult Mice. PLoS ONE 9(2): e88582. doi:10.1371/journal.pone.0088582

Research Highlight: Studying Tumor Suppressor Genes to Develop New Cancer Treatments

Chris Kemp is working to develop more effective, less toxic cancer treatments through genetic research. 

Cancer is a disease that, in one way another, impacts all of our lives. One in two men in the US are at risk of developing cancer, and one in four are at risk to die of cancer.  For women, the risk of developing cancer is one in three; the risk of dying from cancer is one in five.1 In 2013, nearly 1.7 million people in the US were diagnosed with cancer; over 580,000 died. More than 13 million people in this country are living with cancer .2

Cancer develops through a complex multistage process. Environmental damage over time increases the likelihood of genetic mutations, which can eventually cause cells to multiple continuously, leading to cancer. During this process, a number of genetic and environmental factors influence whether the cells affected by genetic mutations develop into cancer cells.

Researchers are working to understand the environmental causes of human cancer, the underlying mechanisms by which these environmental causes act, and the genetic factors that help determine how an individual reacts to various environmental exposures.

One such researcher is CEEH Environmental Mutagenesis & Carcinogenesis ARE (Area of Research Emphasis) Leader Dr. Christopher Kemp. Dr. Kemp runs a lab at the Fred Hutchinson Cancer Research Center. His work focuses on the genetic and biological basis of cancer and on developing more effective, less toxic cancer treatments.

Dr. Kemp uses functional genomics to discover the biological function of genes, and high-throughput screening (an automated process to test the biological activity of a large number of compounds) to systematically test large numbers of genes. He is searching for which genes cancer cells need in order to survive. These genes are weak points that could be attacked with drugs to selectively kill the cancer cells.

Recent research in Dr. Kemp’s lab focuses on a tumor suppressor gene called ARF. This gene has been found to suppress a devastating lung cancer, non-small-cell lung carcinoma (NSCLC). In 2013, Dr. Kemp led a study that found that ARF plays a role in suppressing multiple parts of NSCLC growth and progression. His team exposed genetically engineered mice that lacked the ARF gene (Arf -/-) to the cancer-causing chemical urethane. They found that the Arf -/- mice had shorter lives and higher morbidity from lung tumors than did control mice (Arf +/+ and Arf +/-) .3

The team’s findings suggest that the ARF gene functions as an early defensive response to lung tumors by creating a barrier against tumor growth and malignant progression.

Kemp’s team also used Arf -/- mice exposed to urethane to study the role of ARF in a deadly liver cancer, hepatic haemangiosarcoma. The findings suggest that lack of the ARF gene is one cause of this liver cancer. The ARF pathway, the series of actions among molecules in a cell that makes a new molecule or turns genes on or off, may be a new molecular target to treat patients with this deadly cancer .4

Chris Kemp’s research has convinced him that science is close to making big progress against cancer. He says, “I’m more optimistic than ever before.”
  1. http://www.cancer.org/cancer/cancerbasics/lifetime-probability-of-developing-or-dying-from-cancer
  2. http://seer.cancer.gov/statfacts/html/all.html
  3. Busch SE, Moser, RD, Gurley KE et al. ARF inhibits the growth and malignant progression of non-small-cell lung carcinoma. Oncogene (2013), 1-9.
  4. Busch SE, Gurley KE, Moser RD, Kemp CJ. ARF suppresses hepatic vascular neoplasia in a carcinogen-exposed murine model. J Pathol. 2012 Jul; 227(3): 298-305.

Research Highlight: Diesel Pollution in South Seattle

©2013 clipart.com
The residents of the Georgetown and South Park neighborhoods in Seattle’s Duwamish Valley now know how much diesel exhaust they are exposed to, thanks to the University of Washington School of Public Health and Puget Sound Sage, a nonprofit coalition in Seattle.

A large volume of traffic travels through these South Seattle communities due to nearby highways, industry, train routes, and the Port of Seattle. Sixty percent of neighborhood residents surveyed in 2009 by Puget Sound Sage believed pollution from commercial trucks affected the health of their families. Long-term occupational exposures to high concentrations of diesel exhaust have been linked to respiratory and cardiovascular health problems as well as cancer.

“Residents were most concerned about commercial truck traffic. They see these trucks travel through their neighborhoods every day. They wanted us to monitor pollution levels where people lived,” said Dr. Julie Fox, a researcher in the UW Department of Environmental and Occupational Health Sciences at the UW School of Public Health.

It was in response to community concerns and support from the Kresge Foundation that the University of Washington School of Public Health partnered with Puget Sound Sage to help residents measure levels of diesel exhaust in the two neighborhoods.

"We were able to develop a much more refined understanding of exposure—and the impacts of various sources of exposure--for this area of the city. Using the skills and expertise from UW scientists to respond to community concerns, we were able to provide detailed community-level data on pollutants that are markers of diesel exhaust," said Dr. Fox.

Researchers collected data over a two-week period in summer 2012 and winter 2012-2013 on primary pollutants that serve as markers of traffic-related air pollution. They are 1-nitropyrene, a polycyclic aromatic hydrocarbon that is a by-product of combustion from diesel engines; black carbon, and particulate matter less than 2.5 μm in diameter.

The researchers also compared these measurements to pollutants measured in residential sites in Queen Anne and Beacon Hill, which are located atop hills and have less commercial truck traffic.

Results indicated that residents of South Park and Georgetown are likely exposed to higher levels of diesel exhaust than residents of the Beacon Hill and Queen Anne. Also, within the two Duwamish Valley neighborhoods, pollution levels varied, even across small areas, and residents near busy roads and industrial areas faced higher levels of diesel exhaust pollution.

Other UW Environmental and Occupational Health Sciences researchers involved in the DEEDS study include CEEH Deputy Director Dr. Joel Kaufman, Jill Schulte (MPH, 2013), Dr. Sheryl Magzamen, a former postdoctoral research scientist, and Nancy Beaudet, of the UW Occupational and Environmental Medicine Clinic.

A report on findings from the DEEDS study are published online.

-- Elizabeth Sharpe, Marilyn Hair




A Trip to the Elwha - Part 7, Freeing a River

© Jon Sharpe, 2013
(Continued from Part 6 of this series, "A Perfect Storm of Opportunity.")

The Elwha River is flowing free, but the restoration project is ongoing. As of this writing, repairs continue at the Elwha Water Facilities Project, clogged with sediment since April. Deconstruction of the Glines Canyon Dam is delayed until the Water Facilities Project is repaired, to prevent the river from transporting the huge amount of sediment trapped behind the remaining portion of that dam.


Current updates are posted on the National Park Service Dam Removal Blog. The updates below were posted on August 6, 2013. Also, check out the Elwha River Restoration on Facebook.


Sediment

The river continues to erode sediment downstream, even during the low flow of the dry summer months. In some locations the river has eroded the sediment down to the original riverbed. A sediment team is conducting monthly aerial surveys of the Elwha River to monitor erosion and re-deposition of the sediment.

Re-Vegetation

In March, Elwha re-vegetation crews sowed 1,400 pounds of native plant seeds in the lakebeds of former Lake Aldwell and Lake Mills. Crews surveyed the sites planted in 2012 with native species and found a 97% survival rate for 6 species studied. The highest mortality rate was 36% for Douglas fir seedlings; the lowest mortality rate was 1% for black cottonwood. In August, crews are planting 41 additional plots in the lake beds and collecting data on ground cover and species abundance.


Vegetation grows on the lakebed of former Lake Aldwell. Re-vegetation crews have planted native seeds on the sites of the former reservoirs.

Fish
The Washington Department of Fish and Wildlife is installing a fish weir on the river downstream of the former Elwha Dam site. The state will use the weir to count and collect fish as part of a multi-agency effort to monitor the influence of dam removal on salmon and steelhead returns to the river, and to minimize harm during the dam removal to the federally-listed, threatened steelhead and Chinook.

Beach

The plume of sediment coming out of the mouth of the Elwha continues to change and shape the beach. The sediment is forming sandbars and large pools where none were before.

A 2012 National Park Service Elwha River Restoration handout reads: The returning salmon and restored river will renew the culture of the Lower Elwha Klallam Tribe who have lived along the river since time immemorial. Tribal members will have access to sacred sites now inundated by the reservoirs. Cultural traditions can be reborn. 


The last stop on my Environmental Health Field Trip was at  the Lower Elwha Gallery & Gift  Shop in Port Angeles where I bought a children's board book, Sharing Our World, Animals of the Native Northwest Coast. One page reads, "Salmon have always been our most important food source. We can protect salmon by keeping our rivers and oceans clean."


The river will never be the same as before the dams, but the habitat is improving and the fish are coming back. The Elwha is on its way to becoming what dam-builder Thomas Aldwell described over 100 years ago, "a wild stream crashing down to the Strait".


Thank you for reading. Here are some resources to help you take your own environmental health field trip to the Elwha River.
- Marilyn Hair


Sources:
Lower Elwha Klallam Tribe Facebook page 
Mapes, Lynda. Elwha A River Reborn. Seattle: The Mountaineers Books, 2013.