Environmental Factor, July 2008, National Institute of Environmental Health Sciences

Wilson Reports on State of the Institute at May Meeting

By Eddy Ball
July 2008

Wilson said that NIEHS is proactive in pursuit of its bottom line of "scientific excellence" in all areas of research and has a "future that is stronger than the past." (Photo courtesy of Steve McCaw)

University of Pittsburgh Department of Pharmacology Chair Bruce Freeman, Ph.D., spoke in support of "out-of-rank" decisions. "We're very glad for our investigators when you reach out and make these special motions of raise-to-pay to support promising research." (Photo courtesy of Steve McCaw)

Other Council members seemed to agree with George Leikauf, Ph.D., who observed after Wilson's presentation, "I think we're going in the right direction." (Photo courtesy of Steve McCaw)

Copeland noted at the beginning of his scientific talk that "mitochondrial medicine is now a [trans-NIH] Roadmap proposal that has just been approved by all NIH directors." (Photo courtesy of Steve McCaw)

Wilson welcomed two new members to the Council - University of Iowa Civil and Environmental Engineering Professor Gerald Schnoor, Ph.D., above, and U. S. Navy Captain Michael Macinski. (Photo courtesy of Steve McCaw)

Contractor Kevin Beverly, above, followed the proceedings carefully. Beverly is the executive vice president of Social & Scientific Systems, which supports the Sister Study and the Epidemiology Support Services Contract for the Institute. (Photo courtesy of Steve McCaw)

On May 29 - 30, the NIEHS National Advisory Environmental Health Sciences Council held its 124th meeting in Rodbell Auditorium. As the first item on its agenda, the members were presented with an encouraging report on the progress NIEHS continues to make toward its goal of scientific excellence.

The presentation by NIEHS Acting Director Sam Wilson, M.D., was dominated by the findings of the recent NIH Office of Management Assessment (OMA) review of NIEHS management practices between 2004 and 2007 that was requested by the U. S. House of Representatives Appropriations Subcommittee. Wilson's report outlined the Institute's process and planning for its Corrective Action Plan, which he estimated could be completed and sent to NIH Director Elias Zerhouni, M.D., as early as June.

"We see the OMA report as a positive step in the management of the Institute," Wilson observed. "We can make use of these findings in a very constructive way... to move ahead." When Wilson opened the floor to discussion, member Dan Liebler, Ph.D., asked for "a little more granularity on the discussion of the [findings of the OMA] grants-making subcommittee," which had questioned the Institute's protocol during the review period in regard to what are known as "out-of-rank order" or "raise-to-pay" awards.

According to Wilson, the issue was not the awards themselves, but rather the documentation to justify them. These kinds of decisions, he added, account for only about one percent of all awards at NIEHS. He said these decisions are usually made to encourage new investigators, foster especially innovative research or broaden the Extramural portfolio to meet needs considered important to the NIEHS mission.

As Executive Secretary and Acting Director of the Division of Extramural Research and Training Dennis Lang, Ph.D., explained, "The problem we faced was that the justification for those decisions, while done appropriately, were not written down and attached to funding plans that became a part of the final record."

Lang reinforced Wilson's commitment to corrective action. "That's a relatively easy thing to fix," he said, "and we started doing that a couple of rounds ago, so at the moment I think we are totally in compliance."

In his review of NIEHS highlights since the last meeting, Wilson lauded the April workshop spearheaded by NIEHS Associate Director Sharon Hrynkow to get NIEHS "to the table during the conversation on climate change, [which is] a key topic in environmental health." He also recognized the ranking of NIEHS by the Scientist survey of training institutions as one of the best places to work for postdoctoral fellows nationally.

Moving on to the trans-NIH initiative on autism, Wilson described the role of NIEHS in leading a Town Hall Meeting at the University of California Davis in May. The meeting, Wilson explained, was part of the process for development of the NIH Interagency Autism Coordinating Committee (IACC) strategic plan for research. "This Town Hall Meeting was very effective and had the structure that was appropriate for getting input [from the community and research scientists]," he said. "The information will be included in the strategic plan as we move forward" (see Extramural Update(http://www.niehs.nih.gov/news/newsletter/extramuralupdate.cfm)).

In addition, Wilson praised several other important developments:

Publication of the National Toxicology Program's Draft Brief on Bisphenol A, which he called "a significant contribution by the NTP in protection of human health"
The U.S. Japan Cooperative Meeting organized by Associate Director Bill Martin, M.D.
The Superfund Basic Research Program/Worker Education and Training Program Workshop in April
Outstanding research publications, highlighting recent Extramural papers on polyketide synthase function(http://www.ncbi.nlm.nih.gov/pubmed/18403714?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum) and proliferating cell nuclear antigen(http://www.ncbi.nlm.nih.gov/pubmed/18316726?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum) and Intramural papers on functional plasticity in hippocampal neurons(http://www.ncbi.nlm.nih.gov/pubmed/18287055?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum) and physiological functions of the Krüppel-like zinc finger protein Gli-similar 2(http://www.ncbi.nlm.nih.gov/pubmed/18227149?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

At the request of members, the meeting returned to the two-day schedule format and included more time for discussion than at other recent meetings.

As this photo of NIEHS Director of Science Policy Joyce Martin, J.D., shows, just because Council meetings are serious business doesn't mean that there's no room for humor. (Photo courtesy of Steve McCaw)

More Time for Discussion… and Science

A more flexible schedule for Council had several benefits for members, not the least of which was an opportunity to hear a talk by NIEHS Principal Investigator William Copeland, Ph.D.(http://www.niehs.nih.gov/research/atniehs/labs/lmg/mdnar/index.cfm) Copeland's talk, "DNA Polymerase λ [Gamma] and Mitochondrial Disease," had been re-scheduled twice. Copeland heads the Mitochondrial DNA Replication Group within the NIEHS Laboratory of Molecular Genetics.

In his introduction of the speaker, Wilson described Copeland's findings as "seminal scientific information that is incredibly exciting."

DNA polymerase gamma (pol λ), Copeland explained, functions to replicate mitochondrial DNA, which in turn is responsible for the body's energy production. Defects in mitochondrial DNA (mtDNA) can lead to a long list of diseases that can affect anyone during a lifetime and impact a variety of tissues, especially the heart, brain, liver and kidneys, which are organs that utilize substantial amounts of energy.

Direct mitochondrial diseases affect about 1 in every 2000 births, with about half developing in childhood and the other half presenting in adults, and mitochondrial deficits have a secondary role in many other diseases, such as Parkinson's Alzheimer's, Huntington's and diabetes. About ten percent of autistic children show biomarkers of mitochondrial disease.

Like nuclear DNA, mtDNA is sensitive to mutagens and carcinogens, including some anti-cancer and anti-viral drugs. Because it is the only known DNA polymerase in mammalian mitochondria and a gene frequently found mutated in mitochondrial disease, understanding the role of pol λ dysfunction by mutations in the POLG gene may be useful in discovering ways to intervene in mitochondrial disease and other diseases where mitochondrial DNA depletion and mutation play a role.

Copeland explored additional mitochondrial diseases in a review(http://www.ncbi.nlm.nih.gov/pubmed/17892433?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum) he published earlier this year in Annual Review of Medicine. A report on a lecture about mtDNA replication by Sherine Chan, Ph.D., a research fellow in Copeland's group, also appears in the Science Notebook section of this issue.

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