HESI holds first workshop on Mouse Liver Tumors. This workshop was the first in a series jointly hosted by HESI, ILSI RSI, and the US EPA. The output of these workshops was foundational in informing the International Program on Chemical Safety (IPCS) conceptual framework for evaluating chemical mode of action.
HESI was founded as a
sciences division within ILSI.
(First meeting held
April 5, 1989)
HESI launches its first four technical committees.
Dr. Denise Robinson appointed as HESI’s first Scientific Director.
HESI launches its first four technical committees:
Carcinogenicity Technical Committee
Immunotoxicology Technical Committee
Water Quality Technical Committee
Waste Management Technical Committee
HESI ITC’s role is unique in that it facilitates tri-partite collaborations. It is very responsive to ‘grass-roots’ proposals and therefore has a unique ability to efficiently address questions raised by bench scientists with a good understanding of big picture questions, and it provides strong project management with managers that are also good scientists. For instance, the ITC played an important role conveying that one CRA assay does not fit all – that flexibility in assay design is good. The ITC impacts contributors’ careers by providing growth opportunities and increasing expertise.”
Dr. Hervé Lebrec, Amgen
Dr. Denise Robinson
Dr. Robinson worked as the inaugural Executive Director of HESI from 1992 – 2002, during which time she established much of HESI’s initial governance and programmatic infrastructure. During her tenure, Dr. Robinson greatly increased the number of active programs, HESI membership, and global reach. Dr. Denise Robinson earned her PhD in Pharmacology from Georgetown University School of Medicine. After leaving HESI, Dr. Robinson worked as the head of Science and Technology, Drug Safety R&D at Pfizer for over ten years. She is currently retired and resides in Connecticut, while continuing to devote time to professional organizations such as the Society of Toxicology.
HESI takes an early lead in exploring non-animal methods for safety assessment with the launch of the Alternatives to Animal Testing (AAT) Technical Committee. The Committee’s research, with expert guidance from international safety assessors, ophthalmologists, and vision researchers, contributed to the abandonment of the in vivo Draize eye test in favor of in vitro approaches.
The Water Quality Technical Committee holds a three-day workshop on Disinfection By-Products in Drinking Water with support from the US EPA, US NIEHS, UK Water Industry Research Council, Chlorine Institute, and the American Water Works Association.
The Developmental and Reproductive Toxicology (DART) Committee launches with an initial project focused on conducting extensive literature reviews on non-traditional developmental toxicity endpoint measurement approaches.
The HESI Peroxisome Proliferation Activated Receptor (PPAR) Committee rapidly launches a blinded pathology review study to address emerging concerns about potential carcinogenicity of drugs and chemicals with this mechanism of action.
HESI celebrates its 10 year anniversary with ~100 supporting organizations (about half private sector and half public sector). To see how we have grown to more than 300 members in 2019, click here.
The Water Quality Technical Committee holds a three-day workshop on Disinfection By-Products in Drinking Water with support from the US EPA, US NIEHS, UK Water Industry Research Council, Chlorine Institute, and the American Water Works Association resulting in a comprehensive textbook on best practices for protecting human health.
The Developmental and Reproductive Toxicology (DART) Committee launches with the goal of conducting extensive literature reviews on non-traditional developmental toxicity endpoint measurement approaches. Since its inception, DART has gone on to publish dozens of fundamental, peer-reviewed studies and original research that form the basis for best practices for DART assessment of chemicals and drugs worldwide.
Several publications that came from the HESI-DART committee (2nd species papers; inhibin B paper; micro-CT evaluations of skeletons) were extremely useful to our organization and the regulatory environment surrounding our activities. The 2nd species paper and micro-CT papers were useful to demonstrate the importance of rabbits in developmental toxicity testing and the validity of using micro-CT evaluations in toxicity studies, respectively."
Dr. Dinesh Stanislaus, GlaxoSmithKline
The HESI Peroxisome Proliferation Activated Receptor (PPAR) Committee rapidly launches a blinded pathology review study to address emerging concerns about potential carcinogenicity of drugs and chemicals with this mechanism of action. The study results were published in a foundational paper that still informs human relevance evaluation for hemangiosarcomas observed in safety studies.
This project pointed out to me how issues that had urgency could be addressed quickly through the HESI process, again bringing together international experts from government, academia, and industry. It also pointed out the success of HESI in being able to handle logistical and scientific issues in an expeditious manner, addressing the specific needs of the sponsors and committee members."
Dr. Samuel Cohen, University of Nebraska Medical Center
HESI is incorporated as an independent 501(c)(3) nonprofit charitable organization with its own governance, financing, and oversight.
The Alternatives to Carcinogenicity Testing Committee publishes the results of a multi-year, 30 million dollar study evaluating six distinct transgenic rodent assays.
Dr. Michael Holsapple is hired as HESI’s second Executive Director.
Agricultural Chemical Safety Committee project receives multiple international awards for reducing animal usage and enhanced testing efficiency.
HESI's active scientific committees:
Alternatives to Animal Testing
Alternatives to Carcinogenicity Testing
Developmental and Reproductive Toxicology*
The HESI role in the Alternatives to Carcinogenicity Testing project was a great example of the power of the model and the ability of this model to foster evolution of scientific thinking in an area critical to promoting human health. There were many individuals involved in making this project a success and it was the environment created by HESI that enabled this remarkable cross- functional effort to be so effective. It is clearly a model that has been perpetuated and enabled continuing contributions to the many challenges we face.”
Dr. Jim MacDonald, Chrysalis Pharma Consulting Former Chair of the HESI ACT Program
Nonclinical/Clinical Safety Correlations
Risk Assessment Methodologies
*These two committees are still active with evolving portfolios in 2019
2001 HESI Staff
Seated (from left): J. David Sandler, Scientific Project Manger; Amy M. Burk Fredericks, ILSI HESI Branch and Board Administrator; Karluss V. Thomas, Scientific Project Manager. Standing (from left): Denise Robinson, Ph.D., Executive Director; Cynthia J. Nobles, Senior Secretary; Syril D. Pettit, Scientific Project Manager; Candice Y. Hamilton, Senior Secretary. Not pictured: Mary Anne Hazen, Senior Secretary; Eric L. Moore, Senior Secretary.
The Technical Committee on Agricultural Chemical Safety, a multi-sector, international group of government, academic, and industry scientists, completes a multi-year project to develop an improved testing scheme for assessing the safety of crop protection chemicals. The program receives multiple international awards and citations for reducing animal usage and enhanced testing efficiency. Program outputs are incorporated into tiered testing guidelines across the globe and reduce overall animal testing.
The Health and Environmental Sciences Institute (HESI) Agricultural Chemical Safety Assessment (ACSA) represented an early effort to reduce the number of animals and resources used in chemical safety evaluation by designing a tiered testing paradigm that incorporated existing knowledge of toxicity and exposure. This effort was an important springboard to the current efforts to increase the efficiency and effectiveness of toxicity testing through use of modern technologies to provide the most relevant information for decision-making.”
Dr. Vicki Dellarco, U.S. EPA (retired)
The Alternatives to Carcinogenicity Testing Committee publishes the results of a multi-year, 30 million dollar study evaluating six distinct transgenic rodent assays. The results of this study inform International Conference on Harmonization guidelines for these assays and their acceptance by regulatory authorities including the FDA, EMA, Japan, Health Canada, and other drug safety agencies around the world.
The success of this project is a strong recommendation for the tripartite approach that HESI is promoting. It was decided that ICH Guideline S1B would give companies the opportunity to use transgenic mice if further evaluated. This recommendation took place after evaluation of the HESI project and as a consequence, a lot of companies have replaced the two-year mouse study.”
Dr. Jan Willem van der Laan, Medicines Evaluation Board
Dr. Michael Holsapple
Dr. Michael Holsapple holds a PhD in Pharmacology & Toxicology from Purdue University and was the Executive Director of HESI from 2002 – 2011. Throughout all stages of his career, Dr. Holsapple has maintained an interest in immunotoxicology, including the importance of developmental immunotoxicity testing.
In response to global health concerns about unanticipated arrhythmias caused by marketed drugs, HESI undertakes a multi-site experimental program to inform novel safety testing that led to global safety practices.
Opportunities to enhance exposure-driven approaches to integrating biomonitoring data in human health risk assessment are highlighted in two pivotal publications by the HESI Biomonitoring Committee.
The value and limitations of DNA adduct data for assigning mode of action for tumor development is the focus of discussions and publications from multi- disciplinary international team of safety scientists within the DNA Adducts Committee.
In response to global health concerns about unanticipated and potentially lethal clinical arrhythmias associated with marketed drugs, HESI undertakes a multi-site experimental program to inform novel safety testing approaches. The results of this study published in 2006 - Hanson et al. – inform novel global cardiac safety standards and effectively eliminate the development of drugs with unanticipated arrhythmic effects.
There is no other place, besides the HESI Cardiac Safety Committee, where there is this breadth of expertise and cross-sector partnership focused on an area of fundamental scientific need. And although we don’t often think about this because we’re focused on advancing our pharmaceutical and environmental safety assessment processes, but cardiovascular disease is the number one cause of mortality globally. There are significant public health impacts that can come from what we study and the capabilities we develop in this HESI program."
Dr. Brian Berridge, National Toxicology Program NIH
HESI Genomics Committee publishes its seminal evaluation of the use of genomic microarrays for chemical and pharmaceutical risk assessment in EHP. These articles have since received ~500 citations and thousands of downloads. The effort led to the launch of the first public microarray database that included experimental animal data (Tox-ArrayExpress) and spurred other efforts such as the MAQC (consortium on genomic data quality) and contributed to the identification of novel renal and genetic toxicity biomarkers.
The project wouldn’t have happened [without HESI]. HESI brought people together to collaborate. HESI can bring people together to do a huge research project that no one else would do – this is very valuable."
Dr. Jennifer Fostel, NIEHS / NIH
Challenges and opportunities to enhance exposure-driven approaches to integrating biomonitoring data in human health risk assessment are highlighted in two pivotal publications in Environmental Health Perspectives and Toxicological Sciences by the HESI Biomonitoring Committee in 2006. These papers have been cited hundreds of times in the last ten years and continue to inform contemporary practice.
The value and limitations of DNA adduct data for assigning mode of action for tumor development is the focus of discussions and publications from multi-disciplinary international team of safety scientists within the DNA Adducts Committee. This program led to the formation of the current Genetic Toxicology Technical Committee that has become a global leader in the design and evaluation of methods of genotoxicity testing.
[Health Canada] fully appreciates the strength of the tri-partite approach used to advance applications and uptake of new tools and approaches. The HESI portfolio within GTTC is impactful, hitting all of the latest important topics and helping to advance and improve genetox methodologies. Working together alongside our industry and academic partners’ issues and challenges facilitates arriving at consensus. In addition, much of the work feeds directly into critical international exercises like revisions of OECD test guidelines, which are necessary to ensure the protection of human health.”
Dr. Carole Yauk, Health Canada
FDA and EMEA ‘qualify’ two novel urinary biomarkers of kidney toxicity (in rodents) for use in safety assessment based on results of a multi-year, multi-site experimental study conducted by the Biomarkers of Nephrotoxicity Committee.
HESI’s 3rd Executive Director, Syril Pettit, launches her first full year in the leadership role and leads HESI’s first Annual Meeting in Europe (Prague) in June 2012.
The first three RISK21 framework manuscripts are published and available for download online. These papers explain a transparent, scientifically accountable, and highly visual approach for performing accurate risk assessments in the 21st century.
HESI celebrates its 25th anniversary and expansion of the scientific portfolio to includes 13 scientific committees and more than 60 distinct projects. Over 260 HESI publications are cited almost 5,000 times in over 1,000 scientific peer reviewed journals.
HESI signs MOU with FDA CDER stating a shared commitment to improving human health via enhanced regulatory science partnerships.
Dr. Syril Pettit
Syril Pettit became the HESI’s third Executive Director in November 2011 after serving in other scientific staffing and leadership roles at HESI since joining the organization in 2000. During her tenure, she has expanded the organizational scope and membership and increased HESI’s focus on multidisciplinary solutions to public health problems. Dr. Pettit launched HESI’s highly recognized THRIVE initiative in 2015.
Dr. Pettit holds a Doctorate in Public Health Leadership (DrPH) from the University of North Carolina’s Gillings School of Global Public Health, a Master’s Degree in Environmental Management (M.E.M.) from Duke University’s Nicholas School of the Environment, and a Bachelor’s Degree in Biology from Amherst College. She has authored dozens of scientific articles and lectured at international scientific meetings around the world on topics including public health, oncology, cardiac safety, genomics, collaborative approaches to science, and other drug and chemical safety issues.
The HESI Protein Allergenicity Technical Committee (PATC) holds a Beijing workshop on food allergy and safety assessment on protein allergenicity and toxicity, clinical allergy, and the safety of genetically modified crops, fostering future collaborations with Chinese scientists and regulators.
[The PATC] studies were related to evaluating the relevance of digestibility as a determinant of allergenicity and to assessing whether bioinformatic sequence comparisons should be based on identity or similarity. The outcome of these studies has provided new leads for studies on the process of sensitization and symptom elicitation in food allergy, and for studies on IgE cross-reactivity.”
Dr. Ronald van Ree Academic Medical Center University of Amsterdam
FDA and EMEA ‘qualify’ two novel urinary biomarkers of kidney toxicity (in rodents) for use in safety assessment based on results of a multi-year, multi-site experimental study conducted by the Biomarkers of Nephrotoxicity Committee. These markers are now routinely utilized non-clinically, have been incorporated into commercial testing platforms, and are under evaluation for clinical use.
The multi-laboratory study data generated by the HESI Biomarkers Committee represent an important contribution to the biomarker qualification process. The FDA recognizes the significant effort that went into generating these data, and that they represent the outcomes of the first prospectively and collaboratively designed, executed, and analyzed qualification studies submitted as part of the BQDS process.”
Dr. Janet Woodcock Director the FDA’s Center for Drug Evaluation and Research
HESI Genetox Committee publication wins Society of Toxicology’s Risk Assessment Specialty Section Best Paper award and the Environmental and Molecular Mutagtenesis Editor’s Choice.
COMPARE – HESI’s first public, curated, protein allergenicity database is released and is rapidly adopted as a global standard for safety evaluation.
HESI reaches a new membership high with scientists participating from more than 300 academic, government, NGO, research, and business organizations around the world
HESI THRIVE program recognized by the U.S. White House Cancer Moonshot Program and the Biden Cancer Institute.
HESI signs MOU with EPA to signal shared commitment to environmental science.
Results of HESI’s multi-year ring trial on methods to assess aquatic bioaccumulation in fish are incorporated into new OECD test methods (319A and 319B) and guidance documents.
HESI signs MOU with EPA to signal shared commitment to environmental science and launch a novel collaboration to improve the utility of modeling approaches for predicting absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species.
HESI THRIVE program recognized by the U.S. White House Cancer Moonshot Program for its innovative approaches to driving research that can improve cancer patient quality of life. This same program is named as one of only 30 partners recognized by the Biden Cancer Institute.
Findings of these innovative THRIVE studies will contribute essential evidence focused on minimizing treatment toxicities that impede quality of life - an outcome that is central to making good on the promise of providing patient-centered care that improves the lived experience for cancer patients and their families. HESI brilliantly dovetailed THRIVE's work with the Biden Cancer Moonshot activities to spotlight this broader constellation of cancer research priorities.”
Rebecca Kirch, National Patient Advocate Foundation
COMPARE – HESI’s first public, curated, protein allergenicity database is released and is rapidly adopted as a global standard for safety evaluation. CompareDatabase.org
HESI has been a very effective coordinator for the different voices of the tripartite membership. This composition has made the outcome very useful and, being consensus-driven, reflective of the science behind the allergy hazard assessment. The usefulness derives from the efforts to make the COMPARE Database clearly derived from literature references with data that meets clear performance goals and are peer reviewed. I think COMPARE has had a big impact on how we move forward on the toxin database or sequence comparisons.”
Dr. John Kough, U.S. EPA
Results of HESI’s multi-year ring trial on methods to assess aquatic bioaccumulation in fish are incorporated into new OECD test methods (319A and 319B) and guidance documents.
HESI becomes a fully independent organization by concluding its charter with ILSI.
The field is moving away from live animal testing to alternative methods of risk assessment – this is very easy to say and really hard to do. HESI has helped advance methods for getting away from animal testing and has accelerated progress. When you get more people focusing on the same question, you bring more resources and more energy – you accelerate progress. HESI has done that.”
Dr. John Nichols, U.S. EPA
Over the past 30 years, HESI science has been implemented around the world to improve decision-making, enhance human health and safety, and preserve the environment. Looking forward to the next 30 years, HESI is excited to continue creating a collaborative environment for scientists from academia, government, industry, and NGOs to come together to create science-based solutions for a healthier world.