Environmental Factor

October 2011


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Toxicology and infectious disease research: Is it time for more collaboration?

By Bono Sen
October 2011

Mike Humble, Ph.D.

Humble, above, organized the workshop as four sessions of talks, each followed by panel discussions that sparked a lively exchange of ideas about the interplay and synergy of exposures in causing disease. (Photo courtesy of Steve McCaw)

Angelika Tritscher, Ph.D.

Making the workshop's overview presentation, Tritscher urged the audience to stop the silo thinking about infectious and environmental agents and begin to think globally, both in terms of cause and in terms of geography. “[In today's world,] disease is only a plane flight away,” she said. (Photo courtesy of Steve McCaw)

Paige Lawrence, Ph.D.

As part of the panel discussing Toxicant Modification of Pathogen Etiology, Lawrence, right, struck a chord that reverberated throughout the workshop about disease etiology, when she said, “I think there's never going to be a single factor.” (Photo courtesy of Steve McCaw)

left to right panelists, Kaylon Bruner-Tran, Ph.D., William Busse, M.D., and Robert Roth, Ph.D.

Pathogen Modification of Toxicant Etiology panelist William Busse, M.D.(http://www2.medicine.wisc.edu/home/people-search/people/staff/204/BUSSE_WILLIAM_W/) Exit NIEHS, center, added the hygiene hypothesis into considerations of host susceptibility. “If you go to daycare early in life,” he said, “you may be protected [from the effects of exposure to some endotoxins].” Seated beside him are Kaylon Bruner-Tran, Ph.D.(https://medschool.mc.vanderbilt.edu/facultydata/php_files/part_dept/show_part.php?id3=1964) Exit NIEHS, left, and Robert Roth, Ph.D.(http://cit.msu.edu/faculty/roth.html) Exit NIEHS (Photo courtesy of Steve McCaw)

John Groopman, Ph.D.

Groopman presented impressive figures on the synergy of exposure to hepatitis B virus and aflatoxin in increased risk for liver cancer. Exposure to aflatoxin alone confers a relative risk of 7.3, but in combination with exposure to hepatitis B, relative risk rises to 59.4. (Photo courtesy of Steve McCaw)

Vincent Young, M.D., Ph.D. and Jennifer Nyland, Ph.D.

Looking back on what participants unanimously considered a productive workshop experience, panelist Vincent Young, M.D., Ph.D.(http://www.cmp.msu.edu/faculty/youngv.htm) Exit NIEHS, left, referred to the interdisciplinary gathering as a place where we're all uncomfortable, because no one can assume the role of expert. He added, “You always think best when you're a little unbalanced.” Seated beside him is Jennifer Nyland, Ph.D.(http://pmi.med.sc.edu/JNyland.asp) Exit NIEHS (Photo courtesy of Steve McCaw)

Come each September, it's time for the spike, marking the annual upsurge in asthma cases. With nearly 200,000 children visiting the emergency room with asthma flare-ups each September, it was fitting that NIEHS hosted a workshop Sept 8-9 to bring together public health professionals and toxicologists for an exploration into the interplay of infectious diseases and environmental exposures in the etiology of human disease.

Facilitated by NIEHS Health Scientist Administrator Mike Humble, Ph.D., the workshop examined the state of the science to determine the gaps and set directions for future research initiatives in the field. The meeting represented a joint effort by NIEHS and the National Institute of Allergy and Infectious Diseases (NIAID), and their grantees to encourage future collaborations.

NIEHS Deputy Director Rick Woychik, Ph.D., opened the workshop by pointing out that separation of environmental exposures and infectious agents is problematic. Highlighting key concepts of a review(http://ehp03.niehs.nih.gov/article/info:doi/10.1289/ehp.0901866) published in Environmental Health Perspectives in 2010 by Ellen Silbergeld, Ph.D., Woychik set the stage for presentations and panel discussions featuring a series of respected researchers in both fields.

An interplay of factors

As the first keynote speaker, Angelika Tritscher, Ph.D., of the World Health Organization, explored One Health Initiative(http://www.onehealthinitiative.com/index.php) Exit NIEHS problems, such as emerging zoonotic diseases and food-borne illnesses, underscoring the need to bring together the disciplines of environmental health and infectious diseases. Later in the meeting, NIAID grantee Gregory Gray, M.D.(http://www.epi.ufl.edu/?q=node/216) Exit NIEHS, returned to these themes in his discussion of his work at the University of Florida Center for Emerging Infectious Diseases.

How something from the environment influences the development and function of the immune response and affects its ability to fight infection was a topic that emerged early in the workshop. Dioxin appears to do so by decreasing T-cell function and also increasing inflammation in the infected lung, according to Paige Lawrence, Ph.D.(http://lifesciences.envmed.rochester.edu/test/index.html) Exit NIEHS, whose research focuses on characterizing molecular mechanisms by which pollutants change the immune system's ability to respond to respiratory infections. “Inflammation is important for fighting infection, but too much inflammation is detrimental,” she explained.

“What is the impact of inflammatory responses in obesity and type 2 diabetes?” John Groopman, Ph.D.(http://www.jhsph.edu/faculty/directory/profile/3683/Groopman/John) Exit NIEHS, was curious to know, given the huge public health implications of these diseases. Because the immune response is suppressed by multiple environmental exposures, the link between such diseases and infections could not be explained solely by a simple mechanism. The timing of infection and exposure are critical, Groopman noted, and the answer may be more than immune response alone can explain.

Rethinking intervention strategies

Fernando Polack, M.D.(http://pediatrics.mc.vanderbilt.edu/directory.php?did=7978) Exit NIEHS, called for a combination of environmentally and genetically driven intervention strategies to improve health outcomes. His research on levels of endotoxin exposure in rich and poor communities of Buenos Aires, Argentina, suggests that early-life exposures to endotoxins can change the innate immune genotype. According to him, intervention strategies that fail to address the disparate environmental factors associated with the problem leave susceptible populations at a major disadvantage throughout their lives.

Other presenters critiqued the notion of looking at diseases through the lens of a single determinant such as endotoxin. The group dismissed the paradigm of one pollutant, one target, and reiterated the need to look at the totality of response to understand the interactions among the pathogen and environment, and immune response.

Emphasizing actionable science

Along with acknowledgement of the need to understand the mechanisms by which pathogens and toxicants influence each other in the disease process and to prove causality, there was a unanimous recognition of the importance of moving beyond purely mechanistic studies to more translational and actionable science.

“This [workshop] opportunity allowed participants to emphasize additional factors, which are at least as important as individual chemical exposures, and to look at global issues of parasitism, malnutrition, [and] infectious diseases, which often get ignored,” concluded Peter Spencer, Ph.D.(http://www.ohsu.edu/xd/research/centers-institutes/croet/faculty/profiles.cfm?facultyID=520) Exit NIEHS, of the Oregon Health and Science University.

Spencer's observations, and the substance of the presentations and discussions, will be included in a paper organizers plan to submit for publication in the near future.

Citation: Feingold BJ, Vegosen L, Davis M, Leibler J, Peterson A, Silbergeld EK(http://ehp03.niehs.nih.gov/article/info:doi/10.1289/ehp.0901866). 2010. A niche for infectious disease in environmental health: Rethinking the toxicological paradigm. Environ Health Perspect 118(8):1165-1172.

(Bono Sen, Ph.D., is the science education and outreach program manager for the NIEHS journal Environmental Health Perspectives.)

Karl Western, M.D. speaking with colleague

NIAID Senior International Science Advisor Karl Western, M.D., right, was on hand to show his institute's support for expanding collaborations. Western moderated the session on One Disease, One Health and the Emergence/Reemergence of Disease. (Photo courtesy of Steve McCaw)

William Stokes, D.V.M. sitting in the audience

The audience included several NIEHS and NTP scientists, including Rear Adm. William Stokes, D.V.M., center, who leads NTP efforts in alternative testing and in the One Health initiative. (Photo courtesy of Steve McCaw)

William Suk, Ph.D. giving his closing comments

In his concluding remarks, Director of the NIEHS Center for Risk and Integrated Sciences William Suk, Ph.D., commented on the way the workshop brought in people from very different disciplines and perspectives. "Sometimes even arranged marriages work," he said of the cross-disciplinary and cross-divisional energy generated by the workshop discussions. (Photo courtesy of Steve McCaw)

NIEHS/NTP Director Linda Birnbaum, Ph.D.

In her concluding remarks, NIEHS/NTP Director Linda Birnbaum, Ph.D., reinforced the need to move beyond looking for single causes for diseases and focus instead on the intersection of different factors in causing disease. She also looked ahead to working even more closely with NIAID and its grantees in future collaborations. (Photo courtesy of Steve McCaw)



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