History of the Toxicology Forum
(January 2018)

 

In the beginning…

 

The exact origin of an organization as diverse as the Toxicology Forum is easily lost, but in this case, we know the origin precisely. As described by Dr. Philippe Shubik in 1993 it occurred when he was attending a meeting at the Given Institute of Pathobiology (U Colorado) in Aspen, Colorado in 1974. It happened that Dr. Alex Malaspina was attending a meeting at the Aspen Institute during the same week.  

 

Dr. Shubik said the two “met walking down the street, and fundamentally the idea of a toxicology forum grew out of the conversation we had that day. We came from very different parts of society at the time. I was entirely academic, and Alex had the pulse of industry”.  Dr. Malaspina said that the driver was that “there was no mechanism for scientists from many sectors to talk to one another, to debate the issues. Dr. Shubik coined the word ‘Forum’ coming from the Roman forum.” By the next year, the first meeting occurred in Aspen at the Given Institute which has served as the summer home for “scientists from the many sectors, industry, academia, government and also the public interest groups to get together and debate the issues”.  (Shubik; Malaspina 1993).  Dr. Shubik also noted that in the early meetings the intent was to model the operation of the Forum meetings in a manner similar to the Gordon Research Conferences. These are focused on leading edge science in now many topics and are held in small college towns so that the opportunity for participant discussions is enhanced.

 

The Toxicology Forum conducts transparent dialogues among various segments of society concerned with problems in toxicology.  A carefully balanced approach to the topics and issues presented at the Forum, with alternative positions presented for each issue. The unique, non-adversarial atmosphere of Toxicology Forum meetings results in frank and open discussions that do not need to arrive at consensus. From the beginning, transcripts of the presentations, presentation materials and discussions with attributions have been put in the public domain. Anyone who pays registration can attend. These unique features allow the public, other scientists and governments to evaluate what is discussed for content and balance and accountability.

 

Drs. Shubik and Malaspina recognized the opportunity for something like the Toxicology Forum in 1974 and went from an idea to the first meeting in Aspen within one year.  Who were these men?

 

Dr. Shubik was trained as a physician at Oxford and obtained his DPhil under Nobel Prize winning toxicologist Howard Florey and Isaac Berenblum at Dunn School of Pathology. They developed the ‘two-stage’ theory of carcinogenesis. He came to the United States in 1949 and became Professor of Oncology at Chicago Medical School in 1950. He was appointed to the fist US National Cancer Advisory Board in 1972. By 1974, he relocated his laboratory to Nebraska and became the Director of the Eppley Institute for Cancer Research. It was widely discussed that while there, Dr. Shubik became troubled by the lack of communication and collaboration between the major sectors involved in cancer research and treatment, namely the pharmaceutical industry, the government and its regulatory agencies, academia and consumers. He had been involved in the annual cancer symposia held at the MD Anderson Cancer Center on fundamental research in cancer which had a similar objective to the Forum but with an international science focus. Another influence in his thinking is that he had been a practicing oncologist for nearly 20 years. Science needed to be measured against improvements in health.

Dr. Malaspina was a multiple graduate of MIT. His undergraduate degree was in chemical engineering, followed by MSc and PhD (1955) degrees both in nutrition. This work led to publications on feeding complementary food proteins in man, and, on nutritional aspects of heat-treated fats. His academic origins and interests were in nutrition, something that persisted for his long career during which he developed and promoted micronutrient and iron supplement programs in developing countries. He joined Coca Cola as Director of Quality Control in 1961. With the development of more sophisticated regulatory processes in the 1970s, he became deeply immersed in the interface between corporate food science and regulation. He published on food treatment processes, including engineering aspects, holding several patents. In 1974, he was Director of Quality Control of the new Coca Cola Corporation.

Over the more than four decades that have followed since these two men envisioned it, the Forum has remained faithful to their vision, grew and most of all survived. Considering that very contentious issues are discussed every year, many involving issues of high public interest, this has been a remarkable achievement.

Growth and Development of the Forum

The first meeting in Aspen was followed one year later by the first of what was to become the annual meetings in Washington, DC in 1976. By 1978, the Forum had “grown like Topsy” (Shubik 1978). In retrospect, two questions present, ‘why did continued growth occur and how has the organization persisted?’ The answer is the people who participated with such passion and that the discussions made a real difference to science.

Within a few years of the first Aspen meeting, regular meetings also were held in Europe in Geneva, several cities in France and Germany, Copenhagen, Oxford and perhaps most remarkably in Budapest two weeks after the inauguration of the first democratically elected government after the fall of the Berlin Wall. In Europe, Professor Dr. Arpad Somogyi played a key organizational role from his position in the German Department of Health and in the European Commission along with people such as Professor René Truhaut. The trend to push the meetings into new areas to promote international dialogue started with meetings in Nigeria in 1979 and then Istanbul and Beijing in 1988.  Dr. Somogyi also has made crucial contributions to the Toxicology Forum since its inception. While at the Eppley Institute in Omaha he was one of Dr. Shubik’s closer associates, and was intimate in the discussions that led to the formation of the Forum in the US. Later, with his move to Berlin he became the central instrument in setting the ground for the Forum in Europe. With the assistance of the late Prof. Nicolai P. Napalkov, Director General of WHO, Dr. Somogyi was directly instrumental in setting up several meetings of the Forum at Geneva’s WHO Centre International des Congres until 1986. In 1987 he organized the European Forum meeting at the Reichstag in Berlin, and assisted in the organization of Forum meetings in France, the UK, Denmark, Hungary, China, and Nigeria. After his appointment at the European Commission, Dr. Somogyi was successful in establishing Brussels as the permanent venue for the Fall European meetings of the Forum, and has continued to be a central organizer of those meetings as the Vice- President of European Affairs for the Toxicology Forum. 

 

For the first two decades, four people made a large impact on the shape of the programs with the help of many others from academia, industry and government who were critical.  Drs. Shubik (an academic) and Malaspina (private sector) were concerned always for new things that pertained to important issues in toxicology and society. In the early years, two other scientists played a very large role in program development, Dr. Ian Munro of Health Canada in Ottawa and Dr. David Clayson (first at the Eppley Institute and then from Health Canada; see Clayson 2002). Leadership from the US Food and Drug Administration also was important including Herb Blumenthal, Richard Ronk and Gary Flamm. Early industry supporters included Drs. George Scott of Procter and Gamble, Richard Hall of McCormick, and John Kirschman of General Foods. Leading academics such as Professor Donald King at the University of Colorado were also instrumental. This far-sighted group of scientists plus many others supplying suggestions and participation for important meetings made the Forum.

The evidence is that these discussions did make a difference. The record is clear that the important objective of getting people from the four sectors together (scientists from universities, government, industry and consumer groups broadly defined) can be approached in several ways. The first is that these four groups did get together usually with one or more reporters from the trade press. Because the sessions usually focused on issues in anticipation, often by several years, of a regulatory or scientific direction, it was and has been normal for government people to provide a perspective on what science is needed to help make better decisions. This often resulted in harnessing the creativity of the academic and private sector to provide information with greater innovation and opportunity than might have been anticipated. Similarly, the academics and government scientists heard perspectives from the private sector which sometimes led to a different way of considering the problem. This often happens from a lack of familiarity with the tools or process options available to industry. Finally, the record shows that consumer oriented organizations offered perspectives on the kind of information that was needed to provide confidence.

Another general perspective is clear from a review of the archival transcripts of the Forum meetings; that is, the importance these meetings had on the problems that were discussed. Certainly, one factor has been that the people present have always been opinion leaders in toxicology internationally. The period following World War II coincided with an explosion in the production of new chemicals for industrial, agriculture and consumer use. More aggressive steps to reduce mortality from chronic disease saw the introduction of new pharmaceuticals starting with the antibiotics. This was accompanied by changes in regulatory toxicology and increasing challenges in food safety. The science of toxicology was advancing and consumer and political concerns about safety assessments increased greatly with the introduction of new drugs and risks from a wide range of activities.  New awareness of the risks of cigarette smoking (Surgeon General’s report in 1964), fungal toxins such as aflatoxin in food (1961) and pesticides in the environment were brought to wide public attention (e.g. Silent Spring in 1962). In addition, the post- war expansion of travel and trade brought with it a need to develop measures to protect public health and facilitate international regulatory agreement between trading partners (Poulsen 2002).

The record of the Toxicology Forum also can be examined in terms of citations to presentations and discussions in transcripts. Sessions presented at the Toxicology Forum have been cited in journals concerned with cancer, immunology, food technology, toxicology, public policy, and general science (including Science). For issues that were contentious, it is not uncommon to find citations in papers arguing both sides of the issue, which is a testament to the efforts of the organizers to maintain balance. In addition to citations in scientific publications, Toxicology Forum transcripts have appeared in PhD theses, government files and books in multiple languages.

By examination of the literature, several of topics where Forum discussions made a difference can be identified. This list includes the safety assessment of saccharin, butylated hydroxyanisole, heterocyclic amines, some flavorings and colors, and mineral oils in foods. Many safety issues can be identified such as formaldehyde in occupational and consumer environments, allergens in occupational environments and some other chemicals critical to occupational health. Critical pharmaceutical discussions on dose selection, short versus long term animal bioassays, and on classes of compounds such as steroids were held. Environmental chemicals, particularly dioxins, were the subject of many sessions. For each of these materials, the organization was demonstrably important in facilitating discussions on mechanistic issues and standards of evidence. 

Overlaying particular topics such as these was the development of regulatory processes (Poulsen 2000). This included the 15-year discussion to codify many of the toxicology tests used today and the dramatically increased importance of mechanism of action in addition to whole animal toxicology (pharmokinetics, pathology). Above all else this allowed information on the relevance, especially of tumors, to humans including certain rodent bladder and forestomach tumors, as well as nasal cell carcinomas in rats. Critical examples of this include compounds that have thresholds for cancer such as formaldehyde, the alpha-2 micro-globulin rodent carcinogens, and particular strains of rodents for safety assessment, and the important question of human relevance.

Another way to consider the early impact of the Forum is by examination of very timely discussions. Examples of this include the 1992 session on breast implants and other implantable devices on cancer and immune response on the very day the US FDA announced its 14-year ban. A 1993 session on bovine spongioform encephalopathy (BSE) included a presentation by Professor Prusiner who spoke before he received his Nobel Prize for research on prions and well before dramatic regulatory actions were taken by the UK (in 1996). The example of BSE illuminates that discussions outside traditionally perceived areas of toxicology are frequently the subject of sessions.

 

Recent years

 

Programs in the past 15 years have emphasized similar themes with emerging chemicals and pharmaceuticals of concern and issues in human health and the environment.  A strong emphasis on new scientific tools (genomics, proteomics, metabolomics) and how these science tools allow better decisions on safety and benefit are dominant themes. Importantly, there has been increased emphasis on challenging the chronic rodent bioassays in terms of human relevance.  Similarly, alternatives to the chronic rodent bioassay have been the subject of multiple discussions.

 

While the specific issues and regulatory mechanisms may vary depending on the continent and country involved, the make up of Toxicology Forum meetings continues to be a valid and productive way to explore and discuss issues relevant to government, industry, academia and consumer groups. This formula has been embodied in the motto of the Toxicology Forum, “Understanding through Dialogue”.

 

 

Primary Sources:

 

  • Interviews with Drs. Frank Baker, Richard Hall, Don Hughes, Alex Malaspina and Ian Munro.
  • Remarks by Phillip Shubik and Alex Malaspina, Transcript, Winter Toxicology Forum 1993, pages 47–48.
  • Remarks by Phillipe Shubik, Aspen Toxicology Forum, 1978, p.1
  • Presentation by Dr. Emil Poulsen, European Toxicology Forum meeting, 2000 (on-line, www.toxforum.org )
  • Clayson, D. (2000) David Barringer Clayson (1924–2000). Regulatory Toxicology and Pharmacology 32:227.
  • Literature search using academic and other on-line searching methods,
  • Review of Toxicology Forum transcripts.