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Special Sessions

Videos from the Annual Meeting:

Plenary Opening Lecture: Perspectives on Science in the 21st Century
Lecturer: Nobel Laureate Lee Hartwell, Fred Hutchinson Cancer Research Center, Seattle, WA

Merit Award Lecture: The Dose Makes the Toxicologist—Paracelsus As Seen From Switzerland
Lecturer: Hanspeter Witschi, University of California Davis, Emeritus, Bandon, OR

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Plenary Opening Lecture: Perspectives on Science in the 21st Century
Monday Morning, March 17, Time: 8:15 AM–9:15 AM
Exhibit Hall 4F
Lecturer: Nobel Laureate Lee Hartwell, Fred Hutchinson Cancer Research Center, Seattle, WA

Dr. Lee Hartwell didn’t realize as a boy that his youthful predilection for chasing butterflies hinted at his future as a geneticist. Nor did his teen-age tinkering on auto engines give him a clue that he would win a Nobel Prize. But today, his career’s work in cell genetics has changed the way we think about life itself.

Early in his research career, Hartwell set out to find an organism simple enough to experiment on, yet complex enough to provide insight into humans. He made a risky choice: to use yeast, the same single-celled fungus that makes bread dough rise. At the time, most scientists thought yeast was not a good model for understanding the complexity of human cells.

Hartwell persisted, and a series of experiments over several years led to a landmark discovery. He discovered the genes that control cell division-genes that turned out to be the universal machinery for cell growth in organisms from fungi to frogs to humans.

This discovery in yeast not only showed the unity of all life, it also had practical applications for human health.
By identifying “checkpoint” genes that determine whether a cell is dividing normally, Hartwell provided important clues to cancer, which arises from abnormal, uncontrolled cell growth. Hartwell’s discoveries have led him and other scientists to explore ways to stop abnormal cells from dividing. Researchers hope this work will lead to new and better ways to prevent, diagnose, and treat cancer.
For his insightful discoveries, Hartwell received the 2001 Nobel Prize in Physiology or Medicine.

In Vitro Toxicology Lecture AND LUNCHEON for Students
Monday Afternoon, March 17, Time: 12:30 PM–1:20 PM
Sheraton Hotel
Grand Ballroom A
Lecturer: Yvonne Will, Pfizer, Inc., San Diego, CA

Development of In Vitro Screening Tools to Test for Drug-Induced Mitochondrial Toxicities (ticket required)

Sponsored by:
The Colgate-Palmolive Company
Organized by:
The Animals in Research Committee

It is estimated that only 50% of the animal studies predict human efficacy and more importantly human toxicity. In addition, the use of animals should be minimized as much as possible for ethical reasons. Today, there are vigorous, ongoing national and international research and policy efforts to develop alternatives to animal testing. The efforts focus on both in vitro and in silico approaches and methods. For example, the National Toxicology Program (NTP) at the National Institute of Environmental Health Sciences (NIEHS) created the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) in 1998.

Mitochondrial dysfunction is a common mechanism of drug-induced toxicity for a variety of therapeutics, such as certain antiviral drugs, lipid-lowering drugs, NSAIDs and certain cancer chemotherapeutics. Therefore, the early identification of drug candidates that potentially disrupt mitochondrial function is of significant importance in drug discovery. In the past few years we have developed organelle and cell based in vitro screens to detect potential mitochondrial toxicities. These include oxygen sensors to measure mitochondrial respiration in isolated mitochondria and cells, immunocapture of individual electron transport chain proteins that can identify inhibitors of mitochondrial electron transport, and metabolic profiling using oxygen and pH measurements. We discuss the strength and limitations of new applicable high throughput screens and provide recommendations of where to position these assays within the drug development process.

Merit Award Lecture: The Dose Makes the Toxicologist—Paracelsus As Seen From Switzerland
Monday Afternoon, March 17, Time: 12:30 PM–1:20 PM
Ballroom 6B
Lecturer: Hanspeter Witschi, University of California Davis, Emeritus, Bandon, OR

Theophrastus Bombastus von Hohenheim—as he called himself throughout his life—was born in Switzerland (1493) where he lived with his parents during the first few years of his childhood and, later, some 5 years in Basel, St. Gall and its surroundings. The rest of his unruly life he spent traveling; the last few years in Austria where he died in 1541. He is best remembered for the saying “the dose makes the poison”, but his impact on contemporary and later medicine was much broader. Joseph F. Borzelleca gives a vivid description of Paracelsus’ accomplishment in his most readable: “Paracelsus—Head of Modern Toxicology” (ToxSci. 53, 2–4, 2000). In 1993, the Swiss historian Pirmin Meier wrote a book never translated into English “Paracelsus—Arzt und Prophet”, highlighting Paracelsus’ activity in Switzerland. It served as primary source material for adding some details to the work and life of Paracelsus, such as interesting information on his name, on how he looked at disease in a new and holistic manner, his preoccupation with the “invisible diseases”, his “Hippocratic oath” and why he was banned from publishing by the City of Nuremberg in 1530 (most of his voluminous writing was published only after his death in 1541). A few personal reflections on Paracelsus and his role in toxicology will be added.

SOT/EUROTOX Debate: Motion— In Vitro Toxicology is Useful for Regulatory Purposes
Tuesday Morning, March 18, Time: 8:00 AM–8:30 AM
Ballroom 6A
Endorsed by:
Society of Toxicology (SOT)
European Societies of Toxicology (EUROTOX)

Debaters
SOT: George Daston, Procter & Gamble Company, Cincinnati, OH (con)
EUROTOX: Thomas Hartung, European Centre for the
Validation of Alternative Methods, Ispra, Italy (pro)

Each year the SOT Annual Meeting includes a debate that continues a tradition that originated in the early 1990s in which leading toxicologists advocate opposing sides of an issue of great toxicological importance. This year, our debaters will address the proposition: In Vitro Toxicology is Useless for Regulatory Purposes.

In vitro toxicity assays have been in use for a long time and have a large number of applications, but in regulatory settings they are still used largely as preliminary screens rather than as the definitive basis for chemical regulation. A number of reasons underlie the current status of in vitro tests, including that they often do not provide information that is directly usable in risk assessment. Addressing the question of regulatory utilization of in vitro tests is becoming urgent as laws such as the European Union’s 7th Amendment to the Cosmetics Directive come into force, which will not allow ingredients tested in animals after 2013 to be used in personal care products. The debate will present some of the challenges to the use of in vitro toxicity assays as the basis for chemical regulation.

Regardless of framework differences and personal convictions, each scientific delegate will present relevant evidence and compelling scientific arguments to persuade and appeal to the response of the audience in order to obtain the approval or refusal of the motion.

In addition to being a featured session at the Annual Meeting, this debate will again take place from October 5–8 at the 45th Congress of EUROTOX in Rhodes, Greece.

Issues Session: Over-the-Counter Cough and Cold Medications in Children:
Efficacy, Safety, and Use
Tuesday Morning, March 18, Time: 7:30 AM–8:50 AM
Ballroom 6B
Chairperson(s):Charles Vincent Smith, Seattle Children’s Hospital Research Institute, Seattle, WA and Sid Nelson, University of Washington, Seattle, WA
Endorsed by: SOT Presidential Chain

Parents spend around $500 million each year in the U.S. to purchase 95 million boxes containing almost 4 billion doses of over-the-counter (OTC) pediatric cough and cold products, despite the absence of any published evidence of efficacy of these formulations from randomized, double-blind, placebo-controlled studies in children or infants. Both the American Academy of Pediatrics and the American College of Chest Physicians have published statements on the lack of efficacy of these products in children. Nevertheless, many parents, including many parents trained as biomedical scientists, believe that these OTC products provide beneficial effects in their children. Decongestants (alpha-1 agonists) have been linked to cardiac arrhythmias and hypertension, antihistamines with sedation and visual hallucinations, and antitussives with depressed levels of consciousness and encephalopathy, particularly in children under the age of 6 years. A Food and Drug Administration (FDA) review identified 123 deaths in children less than 6 years of age over the last several decades associated with use of OTC cough and cold products. This number has been questioned due to inclusion of examples in which oter factors may have been dominant and, conversely, the identification of true cases may be incomplete. Whatever the true measure, the number of deaths has been interpreted either as small, relative to the millions of children dosed, or as unjustifiable, in absence of evidence of efficacy. Additional concerns are that virtually nothing is known of potentially adverse effects of these products on child development. An advisory panel convened by the FDA in October 2007 produced a vigorous discussion of the need for better data on risks and benefits in children of OTC cough and cold medications. In addition to the direct importance of the topic, this controversy serves as an example of several core issues relevant to toxicologists, regulatory personnel, and consumers. One issue is the recognition that children are not simply small adults, and differences from adults in physiologies and susceptibilities to pharmacological and environmental exposures need to be considered and studied, so that rational judgments and risk/benefit assessments can be made. A second consideration arises from the broader question of how best to use incomplete data for evidence-based risk/benefit evaluations and decision-making processes that can be applied in timely and useful policies. Discussion of these principles will enhance our efforts to identify the most important questions to be addressed by ongoing and future research.

Featured Session: Town Hall Meeting—SOT Strategic Plan—Defining the Future of SOT
Tuesday Afternoon, March 18, Time: 12:00 NOON–1:20 PM
Ballroom 6E
Chairperson(s): George B. Corcoran, Wayne State University, Detroit, MI and Kenneth S. Ramos, University of Louisville, Louisville, KY

The future of toxicology is being debated on multiple fronts. As such, it is imperative for the Society to assess the needs and responsibilities of the membership in leading the evolution of the science and practice of toxicology. In 2005, Council determined that an in-depth review of our direction and organizational structure was warranted and that such an assessment should include broad representation of the membership. Between the summer of 2005 and January 2006, three strategy committees were established to advise Council on future directions in three major areas of Society activities and interests: Science, Communications, and Membership. These groups conducted strategy sessions and carefully reviewed the work of past groups including, the Liaison Task Force, the Recruitment and Retention Task Force, and the Communications Committee. The final reports of the three Strategy Committees were received by Council in April 2007, following member input on-line, at the 2007 Town Hall Meeting, and via correspondence. During the spring, summer and fall of 2007, over four 2-day meetings, Council consolidated strategy reports and member input and developed steps for implementation of a 3-year plan. In addition, areas of diverse opinion have been identified and slated for additional member input. The consolidated Council Strategic Plan, which has been posted on the SOT web site for comment, will be presented at the 2008 Town Hall Meeting. Join members of Council for the official roll-out of the plan to learn what to expect from SOT in 2008–2009 and to share your thoughts on how toxicologists can work together toward creating a safer and healthier world by advancing the science of toxicology.

Gathering Information and Putting the Plan to Paper,
George Corcoran, Wayne State University, Detroit, MI From Plan to Reality: What to Expect in 2008–2009, Kenneth Ramos, University of Louisville, Louisville, KY

Featued Session: Distinguished Toxicology Scholar Award Lecture: Half a Century of Progress in Neurotoxicology: Past, Present, and Future
Tuesday Afternoon, March 18, Time: 12:30–1:20 PM
Ballroom 6B
Lecturer: Toshio Narahashi, Northwestern University Feinberg School of Medicine, Chicago, IL.

Progress in neurotoxicology has come a long way. This presentation highlights the progress in our laboratories during 59 years of my scientific careers. Studies of the mechanism of action of insecticides began flourishing in 1950s when many synthetic insecticides were developed. Our study in 1952 showed that DDT prolonged the depolarizing after-potential of the nerve, suggesting the sodium channel as a target site. This discovery eventually led to voltage clamp studies of DDT and pyrethroids demonstrating the prolonged openings of sodium channels being responsible for their toxic action (1967~). Only 1% of sodium channels needs to be modified by pyrethroids to cause hyperactivity of animals (1994–96). DDT and pyrethroids are unique in that they are more potent in killing insects and in modulating the nervous system at low temperatures than at higher temperatures (1954), and the mechanism lies in the temperature dependence of sodium channel prolongation (1996). Glutamate-gated chloride channels, which are present in insects but not in mammals, are a decisive factor in the selective toxicity of fipronil in insects over mammals (2003–05). We previously demonstrated that the reduced sensitivity of the nerve to insecticides played a significant role in the resistance of insects to insecticides (1958–65). This discovery led to the concept of kdr strains of insects, and eventually to the molecular identification of sodium channel mutations in pyrethroid resistance by many investigators. Another important development occurred in 1960 and 1964 when we discovered the selective and potent sodium channel blocking action of the pufferfish toxin, tetrodotoxin (TTX). This discovery caused explosive uses by many of TTX and other toxins/chemicals as tools for the studies of ion channels, a concept that was almost inconceivable before that time. It eventually led to the development of neuroreceptor/channel-based mechanistic studies of a wide variety of chemicals including neuroactive therapeutic drugs and environmental toxicants (1974). This field now represents one of the most important and popular research subjects in biomedical and toxicological sciences. For example, our recent studies of Alzheimer’s drugs have shown that they stimulate not only the cholinergic system but also the NMDA system, both of which are known to be down-regulated in the brain of Alzheimer’s disease patients (2001–07). Neurotoxicology is now progressing toward the molecular mechanisms of drug action. The role of environmental toxicants in causing certain neurodegenerative disorders is receiving much attention these days.

Keynote Medical Research Council (MRC) Lecture: Biological Energy Conversion and its Toxic Consequences
Wednesday Morning, March 19, Time: 8:00 AM–8:50 AM
Ballroom 6A
Lecturer: Nobel Laureate Sir John E. Walker, MRC Dunn Human Nutrition Unit, Cambridge, UK

Energy in foodstuffs is released by respiration (controlled burning), consuming in the process most of the oxygen that we have breathed in. Of the 1000 or so proteins that are involved, about 100 of them are organized into the respiratory enzyme complexes in mitochondria that function as molecular machines to convert the redox energy derived from food-stuffs into adenosine triphosphate (ATP), the energy currency of biology. The final synthetic step is achieved by a remarkable molecular machine that has a mechanical rotary action. An important toxic by-produce of energy conversion is the production of ROS reactive oxygen species (ROS). ROS are generated during the process of electron transfer, but where and how they are generated remains controversial. The ROS can react with nucleic acids, proteins and phospholipids causing damage to biological processes that may lead to diseases and contribute to ageing. Hence, there is a need to develop drugs to prevent the toxic effects of ROS. All of these issues will be discussed in the lecture.

Featured Session: Meet The Directors Session — A conversation With the Directors: THE NIEHS Strategic Plan
Wednesday Afternoon, March 19, Time: 12:00 NOON–1:20 PM
Chairperson(s): Cheryl Lyn Walker, University of Texas MD Anderson Cancer Center, Smithville, TX

The Meet the Director program is a special 80 minute session that provides an opportunity for the leaders of major federal agencies to engage in a panel discussion of emerging trends in toxicology research and its funding. The session will be a particularly valuable opportunity to update our members on the future directions of the Institute and NTP. There will be a strong emphasis on change of direction and new initiatives that may impact the practice of toxicology in the near and long term. Speakers will identify opportunities where non-agency toxicologists may be able to participate in initiatives of their agencies, and will answer questions of attendees.

Cheryl Lyn Walker, University of Texas MD Anderson Cancer Center, Smithville, TX

Samuel H. Wilson, Director, National Institute of Environmental Health Sciences and National Toxicology Program, Research Triangle Park, NC

William Suk, Deputy Director, National Institute of Environmental Health Sciences and National Toxicology Program, Research Triangle Park, NC

Dennis Lang, Director, Division of Extramural Research and Training (NIEHS), Research Triangle Park, NC

Featured Session: Soapbox Session
Wednesday Afternoon, March 19, Time: 12:00 NOON–1:20 PM
South Lobby, Level 4
Chairperson(s): Harvey Clewell, John Morris, and Hollie Swanson

Each speaker will be allowed to address the audience for up to 10 minutes on a topic they have submitted in advance. Topics can reflect either an area of continuing concern or an issue that has arisen during the meeting, and are expected to be novel, controversial, contrary and/or unpopular. No projector or computer slide capability will be provided, but speakers can hold up a poster as a visual aid if desired. After each speaker, the audience will have up to five minutes to challenge or support the speaker with questions or comments.

Soapbox Session Abstract Submittal Instructions

Soapbox session speaker candidates should email their proposed topics to the chair, Harvey Clewell, or co-chair, John Morris, no later than noon on Tuesday, March 18. The submittal should include the title, presenter, affiliation (if any), and a short (less than 250 word) abstract. They will be contacted with the decision of the chair/co-chair regarding their proposal by 6:00 PM, Tuesday. The decision of the chair and co-chair will be final.

Topics can reflect either an area of continuing concern or an issue that has arisen during the meeting—topics are expected to be novel, controversial, contrary and/or unpopular. They should represent ideas, views, and concerns of interest to the general toxicology community. The Soapbox Session is not intended to serve as a personal forum or a “back door” for rejected abstracts.

Note: No projector or computer slide capability will be provided, but speakers can hold up a poster as a visual aid if desired. Presentations are for 10 minutes with a 5 minute audience participation time.

 

Issues Session: 2007 National Research Council- National Academy of Sciences Reports: Impact on the Future of Toxicology
Thursday Morning, March 18, Time: 7:30 AM–8:50 AM
Ballroom 6B
Chairperson(s):Gerald N. Wogan, Massachusetts Institute of Technology, Cambridge, MA and Cheryl Lyn Walker, University of Texas MD Anderson Cancer Center, Smithville, TX.
Endorsed by: SOT Presidential Chain

This special session has been organized by the 2008 Program Committee to introduce SOT members to the 2007 National Research Council reports from the National Academy of Science addressing key issues impacting our society and profession today. This session will open dialogue on the contents of the reports and their implications for the future of Toxicology. An Introduction by the Session Chairs will be followed by presentations from Chairs of the Committees drafting the three reports to be featured, with a facilitated discussion to follow. These reports are:

Toxicity Testing in the 21st Century: A Vision and Strategy, Daniel Krewski, University of Ottawa, Ontario, Canada

Applications of Toxicogenomics Technologies to Predictive Toxicology and Risk Assessment, David Christiani, Harvard University, Boston, MA

Models in Environmental Regulatory Decision Making, Chris Whipple, ENVIRON Corporation, Emeryville, CA