On Monday, March 20, 2023, I attended the annual SOT/EUROTOX Debate that took place during the 2023 SOT Annual Meeting and ToxExpo at Music City Center in Nashville, Tennessee. This debate is a tradition that started in the early 1990s. It brings leaders in the field of toxicology to debate/advocate opposing sides of an issue that has significant toxicological importance. This year’s debate was on the topic “The Exposome Will Drastically Change the Practice of Toxicology.”
About the Debaters and Chairs
The Debater for SOT in support of the motion was Robert O. Wright of Icahn School of Medicine at Mount Sinai, New York, New York, and the Debater for EUROTOX in opposition to the motion was Robert Barouki of Université Paris Descartes, Paris, France. This debate was chaired by Laurie C. Haws, ToxStrategies Inc., and Félix Carvalho, Universidade do Porto, Portugal.
About the Debate
The debaters explained the concept of the exposome and discussed its opportunities and challenges for toxicity assessments. Specific questions addressed include:
- Is the exposome concept adequately mature to be applied in the assessment of human toxicities?
- Is our understanding of what factors contribute to the exposome sufficiently known?
- Is there a systematic way to measure or model the influence of environmental exposures?
- Are analytical and diagnostic techniques sufficiently advanced to reliably measure the exposome?
- Do we have the necessary mechanistic understanding to allow linking exposures with health outcomes?
- Are we ready to include “all life exposures” in our toxicology practice?
- Are we able to integrate the social exposome with our toxicology practice?
In support of the proposition, Dr. Wright provided the following points:
- Exposomics is an evolution of toxicology and environmental health that is inevitable and continues an overall trend in science toward ’omics. Mendelian genetics was left behind with revolutionized measurement of genetic variation on an ’omics scale (genomics). It begs the question where genetics would be if we test hypothesis using one gene variant per time?
- Exposomics is an exposure science revolution that measures the environment. While it is still developing better exposure tools, it is where genomics was approximately 20 years ago because improved study design and experimental rigor (e.g., methods replication) proceeded genomics.
- Exposomics is not amorphous but like genomics has scientific branches. Genomics is now practiced as multi-omics under the new terminology “trans-omics.” Different standalone disciplines that evolved from genomics and are centered around it include epigenomics, transcriptomics, proteomics, and metabolomics. Whereas, exposomics has divisions including chemical, physical, social, infectious, exposomes, etc., that require the need to bring them together.
- Heritability and complex diseases—what genomics is missing. There are 10–30 times higher heritability estimates in twin studies than it is for genome-wide association studies (GWAS). For example, Alzheimer’s disease is approximately 70% genetic in twin studies but approximately 3% genetic in population-based GWAS. This difference is referred to as “missing heritability” in genetics. In heritability, genes’ work is assumed to be independent of the environment and vice versa. Whereas, biology always shows interactions between genes and the environment, and almost all the missing heritability can be attributed to gene-environment (GxE) interaction.
- There are other things we inherited besides genes that are correlated across generations. These include wealth and poverty, which are drivers of educational attainment, racism, segregation, and cultural practices such as diet, customs, and social networks. Twins share a great deal of environment even if adopted at birth. These factors appear genetic in twin studies because they are studies of family units and less so of populations, capturing a large proportion of “inherited” GxE interaction but referring to it is as “genetic.”
- In laboratory exposome(s), variability in experimental results across labs may be due to several factors, including feed content and quantity, water quality, indoor air quality, temperature variation, light, noise levels, handling procedures, etc.
In opposition, Dr. Barouki provided the following points:
- By definition, exposome is a measure of all life-course environmental exposures from prenatal period onward, including internal body processes, external exposures, and lifestyle factors. Whereas, toxicology is the study of the adverse effects of chemical, physical, or biological agents on living organisms and the ecosystem, including the prevention and amelioration of such adverse effects. While exposomes consider everything, everywhere, all at once, and all over the lifetime, toxicology considers something, somewhere and at the right time.
- The exposome has almost come of age, but we do not know what exactly an exposome study is. Is it a study with few chemicals, different types of stressors, non-targeted screening, or a multi-omics study?
- Exposomics are part of multi-omics approaches but not all ’omics are equal (i.e., exposomics ≠ other ’omics). In multi-omics data, exposomics involves complex exposures while other ’omics (e.g., genomics, proteomics, lipidomics, metabolomics, and proteomics) deal with hazard, mechanisms of action and adverse outcome pathway (AOP).
- Exposome will provide a more comprehensive practice of toxicology, but exposome looks like the addition of exposure sciences and toxicology.
- With exposomics, it is easy to combine exposure and effects, but causality can be supported by human, animal, new approach methods (NAM), and computational approaches plus time matters.
- The exposome is the most innovative 21st-century concept that will influence toxicology practice, but this begs the question on other areas including NAMs, AOP/AON, ’omics, AI, QSAR, DOHaD, PBTK, and NGRA.
- Exposome will support mixture studies, but toxicology already has a mechanism-based strategy for mixture effects (e.g., the TEQ/TEF framework).
- Exposome studies are expected to explore multiple stressors, but toxicology already studies the interaction of chemical stressors with other stressors.
- The exposome includes psychosocial stressors, but experimental assessment of psychosocial stress is possible (e.g., BDNF).
- Since much of the innovation in the field of exposome has already been carried out in toxicology, there is no clarity what drastic change will occur. While scaling up is nice, focus is required in the practice of toxicology and risk assessment.
Conclusion
The audience asked the debaters questions and also made contributions. At the end of the debate, the audience voted by show of claps. Based on the audience’s votes, the Chair concluded that it was a tie.
Future Debate
This debate will take place again during EUROTOX 2023 in Ljubljana, Slovenia, September 10–13, 2023, where the debaters will be take reverse positions.
This blog reports on the SOT/EUROTOX Debate Featured Session that was held during the 2023 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email SOT Headquarters.
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