Gordin Kaplan Award Lecture. Building a relationship: science and the community

An appreciation for the intrinsic relationship that exists among science, scientists, and the public must be established. Both practitioners of science and the public should be made more aware that science is part of everyday life and that the definition of a scientist should be more encompassing. It is generally accepted that the public supports but often does not understand the goals of the scientific community. This is often due to lack of effective communication. The scientific community has accepted accountability to the public and attempts have been made to improve our image. Programs by groups and individuals to interact with the public, particularly school children, have grown. However, there is still a need to expand this area. It is our responsibility to find our niche in science awareness programs as speakers, mentors, or facilitators. Participation in these programs is an essential part of a professional scientist's career and should be encouraged by administration. Interaction with the public improves our ability to explain science in lay terms and the relevance of our work to the community. End points should be established to measure success: not just numbers of students entering "scientific" careers but also science literacy. Developing this strategy will not only improve the image of the scientific community with the public but also build a lasting relationship where needs and aspirations will be mutually appreciated.     

Comments on Gould, PAIN, 74 (1998) 341-343

Journal policies and requirements of funding agencies on financial disclosure of authors and grant applicants have divided editors and scientists who disagree on whether such policies can improve the integrity of science or manage conflicts of interest. Those opposed to such disclosure policies argue that financial interest is one of many interests held by scientists, is the least scientifically dangerous, and should not be singled out. Those who favor open reporting of financial interests argue that full disclosure removes the suspicion that something of relevance to objectivity is being hidden and allows readers to form their own opinions on whether a conflict of interest exists and what relevance that has to the study. The authors believe that the scientific community and the public will be best served by open publication of financial disclosures for readers and reviewers to evaluate.     

The causes and prevention of cancer: the role of environment

The idea that synthetic chemicals such as DDT are major contributors to human cancer has been inspired, in part, by Rachel Carson's passionate book, Silent Spring. This chapter discusses evidence showing why this is not true. We also review research on the causes of cancer, and show why much cancer is preventable. Epidemiological evidence indicates several factors likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors are avoidance of intense sun exposure, increases in physical activity, and reduction of alcohol consumption and possibly red meat. Already, risks of many forms of cancer can be reduced and the potential for further reductions is great. If lung cancer (which is primarily due to smoking) is excluded, cancer death rates are decreasing in the United States for all other cancers combined. Pollution appears to account for less than 1% of human cancer; yet public concern and resource allocation for chemical pollution are very high, in good part because of the use of animal cancer tests in cancer risk assessment. Animal cancer tests, which are done at the maximum tolerated dose (MTD), are being misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half of the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at these high doses. A plausible explanation for the high frequency of positive results is that testing at the MTD frequently can cause chronic cell killing and consequent cell replacement, a risk factor for cancer that can be limited to high doses. Ignoring this greatly exaggerates risks. Scientists must determine mechanisms of carcinogenesis for each substance and revise acceptable dose levels as understanding advances. The vast bulk of chemicals ingested by humans is natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of these natural pesticides tested at the MTD are rodent carcinogens. Reducing exposure to the 0.01% that are synthetic will not reduce cancer rates. On the contrary, although fruits and vegetables contain a wide variety of naturally-occurring chemicals that are rodent carcinogens, inadequate consumption of fruits and vegetables doubles the human cancer risk for most types of cancer. Making them more expensive by reducing synthetic pesticide use will increase cancer. Humans also ingest large numbers of natural chemicals from cooking food. Over a thousand chemicals have been reported in roasted coffee: more than half of those tested (19/28) are rodent carcinogens. There are more rodent carcinogens in a single cup of coffee than potentially carcinogenic pesticide residues in the average American diet in a year, and there are still a thousand chemicals left to test in roasted coffee. This does not mean that coffee is dangerous but rather that animal cancer tests and worst-case risk assessment, build in enormous safety factors and should not be considered true risks. The reason humans can eat the tremendous variety of natural chemical "rodent carcinogens" is that humans, like other animals, are extremely well protected by many general defense enzymes, most of which are inducible (i.e., whenever a defense enzyme is in use, more of it is made). Since the defense enzymes are equally effective against natural and synthetic chemicals one does not expect, nor does one find, a general difference between synthetic and natural chemicals in ability to cause cancer in high-dose rodent tests. The idea that there is an epidemic of human cancer caused by synthetic industrial chemicals is false. In addition, there is a steady rise in life expectancy in the developed countries. Linear extrapolation from the maximum tolerated dose in rodents to low level exposure in humans has led to grossly exaggerated mortality forecasts. Such extrapo     

Mouse-specific carcinogens: an assessment of hazard and significance for validation of short-term carcinogenicity bioassays in transgenic mice

1. The International Conference on the Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for human use (ICH) has agreed that bioassay data from only one species, the rat, supported by appropriate mutagenicity and pharmacokinetic data and also information from new (unvalidated) short term in vivo screening tests for potential carcinogenicity, could be used for the licensing of human medicines. This proposal has been supported by reviews of the utility of testing pharmaceuticals in the mouse which have concluded that the mouse bioassay contributes little to regulatory decisions. The current review was undertaken to identify 'genuine' mouse-specific carcinogens using the Gold Carcinogenicity Potency Database (CPD) for the initial identification of potential mouse-specific carcinogens from published literature. Hazard assessments were completed for these chemicals with particular attention focused on the 'genuine' mouse-specific carcinogens. The significance of such chemicals has been discussed together with consideration of on-going work on the validation of short-term carcinogenicity bioassays using transgenic mice. 2. Seventy-six potential mouse specific carcinogens were identified through the Gold Carcinogenicity Potency Database. Following more detailed consideration a total of ten chemicals were excluded from further consideration (three were multispecies carcinogens, five were considered to be non-carcinogenic in the mouse, and the data for two were uninterpretable). The review focused on the remaining 66 chemicals. There was equivocal evidence of carcinogenicity to the rat for 28 chemicals and inadequate data for a further 23 chemicals. Fifteen 'genuine' mouse-specific carcinogens were identified. These 15 chemicals comprise two genotoxic mouse-specific carcinogens (N-methylolacrylamide (924-42-5), 2,6-Dichloro-p-phenylenediamine (609-20-1); five non-genotoxic mouse-specific carcinogens 2-Aminobiphenyl.HCl (2185-92-4), Captan (133-06-2), Dieldrin (60-57-7), Diethylhexyladipate (103-23-1), and Probenicid (57-66-9); five mouse-specific carcinogens with equivocal evidence of mutagenicity were identified; (2,4-diaminophenol.2HCl (137-09-7), Dipyrone (68-89-3), Ozone (10028-15-6), Vinylidene chloride (75-35-4), and Zearalenone (17924-92-4)), and three mouse-specific carcinogens with inadequate mutagenicity data (Benzaldehyde (100-52-7), Piperonyl sulphoxide (120-62-7), Ripazepam (26308-28-1)). 3. It is suggested that the two genotoxic mouse carcinogens would have been considered as potential carcinogens in the absence of a mouse bioassay. Of the five non-genotoxic mouse-specific carcinogens; three induced tumours in mouse liver only and are considered as being of low potential hazard to human health. The remaining two chemicals would have been missed in the absence of a mouse bioassay (2-aminobiphenyl (2185-92-4) and captan (133-06-2)) and thus are good candidates for evaluation in the short term bioassays in transgenic mice currently being validated. 4. The hardest group of mouse-specific carcinogens to evaluate are those for which there is equivocal or inadequate mutagenicity data. The difficulty in evaluating these particular chemicals emphasises the need for adequate mutagenicity data in addition to adequate carcinogenicity data in order to assess potential hazards to human health. Hazard assessments and a consideration of the potential role for short-term bioassays in transgenic mice for the eight chemicals in this subgroup are presented. 5. A number of general conclusions have been derived from this review. Firstly, there are insufficient published genotoxicity data to allow a full assessment fo mutagenic potential for 57/76 of the potential mouse-specific carcinogens identified from the CPD. This is surprising given the clear value of such data in interpreting bioassay results and the much greater resources required for carcinogenicity bioassays. (ABSTRACT TRUNCATED)     

The micronucleus test and NTP rodent carcinogens: not so many false negatives

In the study by Shelby et al. (1993) on 49 chemicals, the results of the micronucleus (MN) test in mouse bone marrow were compared with the results of the 2 year rodent carcinogenicity assays. Seven of the 25 rodent carcinogens were considered positive in the MN test, 5 following a protocol in which chemicals were given in three daily doses, and a further 2 when the chemical was administered only once. This low rate of positive results has led to disappointment in the MN test as a screen for carcinogens, but a careful examination of the data and of its analysis by Shelby et al. (1993) shows that many of the negative results are appropriate because: of the 18 carcinogens that were negative in the MN test, 1 has been retested and found to be non-carcinogenic, 9 were non-genotoxic and at least 2 were site-of-contact carcinogens not expected to be detected in the bone marrow. Two others were clearly positive in the MN test in other labs. Thus, the MN test 'missed' not 18 carcinogens, but 4 genotoxic carcinogens. The significance of these 4 needs further assessment, since three were liver specific carcinogens and the fourth was a very weak inducer of hemangiosarcomas in female mice only. Overall, the results of Shelby et al. (1993) do not cast such a shadow on the micronucleus test as many feared, and must be examined in the context of all the information available on each chemical. As Ashby and Tinwell emphasize in the accompanying article and in Tinwell and Ashby (1994), the data show that the MN test is capable of identifying human carcinogens and rodent germ cell mutagens, and remains a useful part of genotoxicity evaluation of chemicals.     

A view from the Hill: The human element in policy making on Capitol Hill.

This article examines the process of federal policy making from the perspective of a community psychologist currently working as a congressional staff member. The author describes Capitol Hill as a unique community with its own inhabitants, rules, norms, and social processes. It is only by understanding this culture that members of Congress, staff, lobbyists, scientists, or anyone else hoping to influence the policy process can be effective in shaping legislation. Similarly, the activities in which members of Congress must engage to best understand and represent their constituencies are described as being analogous to those in which ecologically minded community psychologists engage. The primary purpose of this article is to help social scientists understand the policy-making process and the role they can play in influencing that process. It is hoped that the emphasis on the human element will make the process seem less mystifying and more open to influence by scientists who would not ordinarily become involved in federal policy making. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Science and the press: Like oil and water?

Scientists and journalists have traditionally viewed each other warily, but recently scientists from all disciplines have been urged to be more cooperative with reporters. Psychologists, in particular, have more contact with the press than other scientists, and the American Psychological Association has increased its public communications activities substantially in recent years. But if relations are to improve, both scientists and journalists must understand the purposes, values, and procedures of the other. This article reviews the research literature pertinent to the difference in emphases between these two disciplines, the accuracy of scientific reports, and the possibility that the social and behavioral sciences are treated differently by the press than other scientific disciplines. Finally, suggestions for both scientists and journalists are offered to improve cooperation for the betterment of both enterprises and of society. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Research on factors determining health: role of the environment in the 21st century

During the next few decades, actions on matters dealing with environmental pollution will have to be aimed at: 1) eliminating environmental contaminants at the source; 2) identifying biomarkers of exposure and/or adverse health effects; 3) improving our skills at assessing the probability of occurrence of adverse health effects in the community; and 4) informing the Canadian public in a responsible manner. Primary sources of pollution related to human activities should be our deep concern: utilization of energy sources, particularly fossil fuels; agricultural activities, such as deforestation and use of fertilizers and pesticides; and industrialization, responsible for the synthesis of numerous new molecules. Clinical investigators will be faced with rare disease entities characterized by low-level, long-term exposure via food, air, water and soil, and low-incidence responses (e.g. cancer, neurotoxicity, reproductive failure, immunotoxicity). Epidemiologists and toxicologists will be pressed, by the Canadian public, to answer questions regarding the probability of occurrence of health effects as a result of exposure to environmental contaminants. Collectively, as scientists, our attitudes will have to change drastically; high in the order of importance is the need to communicate with the public and to diligently inform our fellow citizens about the relationship between health and environment. In doing so, we might find allies to support our claim that health research in Canada deserves much better support.     

Education of nonscientists about new alcohol research: results of two types of presentations plus 6-month follow-up

Education of nonscientists by scientists is assumed to be beneficial for enhancing public understanding of the research process and increasing public excitement about science. However, evaluation of audience response to receiving such information has rarely been performed. In particular, the effectiveness of communicating new research on alcohol abuse and alcohol dependence has never been evaluated. Evaluation data in the present study show significant knowledge transfer, belief changes, and participant reports of possible behavioral changes in targeted audiences. These occur when alcohol researchers present basic neuropharmacological concepts and new neurobiological research to audiences consisting primarily of chemical dependency counselors, social workers, criminal justice workers, physicians, nurses, family, clergy, and others interested in alcohol-related problems (defined as "clinicians" and the "reachable public"). Together, these results suggest that it is possible to change the beliefs, knowledge, and behavior of chemical dependency clinicians and the reachable public about alcoholism, its causes, and its treatment.     

When psychology informs public policy: The case of early childhood intervention.

The potential of early educational intervention to make a long-term impact on the life chances of socially disadvantaged children has now been clearly demonstrated in research. Yet this article argues that unqualified assimilation of such powerful experimental data into policy carries the risk of perpetuating simplistic models of child development and exaggerating the scope for early intervention. Less attention has been paid to the sense in which long-term effects are embedded in a wider context of family, community, and school processes that affect project children not only at the time of intervention but also throughout their childhood years. It cannot be assumed that such effects will be reproduced in other contexts or at other points in time. The article suggests that failure to incorporate the full implications of a "transactional" model of the transmission of long-term effects into public discussion may in the long run risk undermining public sympathies toward both early childhood programs and this field of psychological inquiry. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delivery of therapeutic drug monitoring services: survey of Australasian clinical pharmacology laboratories

Therapeutic drug monitoring (TDM) services, like many diagnostic services in public hospitals, have been under scrutiny over recent years as funding has decreased. The Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) sought to review clinical pharmacology departments to consider how the changes that have been implemented have affected the delivery of TDM in recent years. A questionnaire was sent to such departments and all those known to be delivering TDM services responded. The survey demonstrated that of the 11 departments contributing TDM assays, 10 had lost tests and staffing to general biochemistry departments; eight departments had been delivering research and development in TDM. The TDM tests retained in clinical pharmacology were typically the more complex chromatographic or labor-intensive toxicology tests or the more expensive immunoassays. If this direction in Australasia is typical of the situation internationally, it should be a matter of great concern to all those with a particular interest in TDM. Is the future of TDM to be one in which only rapid immunoassays will be provided, and by a staff not fully able to provide pharmacokinetic support and interpretation of such tests (i.e., to become simply number-generating services) despite all the pharmacoeconomic data that is increasingly available?     

The role of animal science in natural resource management: current decision making models and future needs

Sustainable systems for land and natural resource management must be biologically, economically, and socially sustainable. Scientists and educators have historically viewed their role as developing new knowledge and technology to enhance biological and economic sustainability. Scientists have traditionally viewed sociopolitical sustainability and policy development as beyond our appropriate roles. Changing public values and perceptions on appropriate land use and natural resource protection are forcing land grant universities and their scientists and educators to re-evaluate traditional paradigms. The animal science community, in concert with the social and other biological sciences, must become more proactive in decision making processes on appropriate land use and natural resource management if we are to remain relevant. This paper describes the current situation and outlines approaches for the research and education communities to be important contributors to collaborative decision making processes on land and natural resource management.     

Sharing and archiving data is fundamental to scientific progress

The persuasive argument for sharing and archiving data is that scientists must build on the shoulders of other scientists, that science is cumulative and replicative, and that science must be open. Sharing and archiving data are just a small part of all that is implied by that principle, but it is inextricably part of our obligation as social and behavioral scientists to conduct our work in the open. Only then can others see and understand what we did, and only then will someone have a chance to confirm that we were right, or to prove that we were wrong. Moreover, data archiving and sharing create opportunities for addressing questions not envisioned by the initial investigators. Indeed, by supplementing or pooling archived data, new and original data sets can be created that permit analyses well beyond the purpose or scope of the initial data collection. Of course, the creativity and labor of initial investigators should be protected, and the privacy of research participants must be safeguarded. These protections and safeguards, however, are not antithetical to data archiving and sharing. They simply raise questions about when and how data archiving and sharing should take place. In our view, the benefits of properly archived and shared data for outweigh the potential for harm. As indicated above, this is a perspective shared by several funding agencies of behavioral and social research, including the NIA.     

Actual situation and problems in the information office of clinical laboratories; questionnaire surveys of central laboratories of university hospitals

The laboratory tests supplied by clinical laboratory comprise an increasing volume in most hospitals. Consultation and effective utilization of laboratory data are important aspects of evidence-based medicine. Effective utilization of laboratory data will also contribute to the efficiency of hospital practice. Questionnaire surveys were conducted to investigate the actual situation in the information office of clinical laboratories in national, public and private facilities of 80 medical universities in Japan. Few facilities demonstrated efficient functioning, although information offices had been opened in six national, one public, and four private universities. The office staff received many questions on specimen handling and analytical methods. In the future, the office will be expected to be actively involved in mutual communications with clinical physicians and an information system such as computerized web is anticipated. Furthermore, a full-time laboratory physician and technicians are expected to provide support as experts in patient diagnosis.     

What do animal cancer tests tell us about human cancer risk?: Overview of analyses of the carcinogenic potency database

Many important issues in carcinogenesis can be addressed using our Carcinogenic Potency Database, which analyzes and standardizes the literature of chronic carcinogenicity tests in laboratory animals. This review is an update and overview of our analyses during the past 15 years, using the current database that includes results of 5152 experiments on 1298 chemicals. We address the following: 1. More than half the 1298 chemicals tested in long-term experiments have been evaluated as carcinogens. We describe this positivity rate for several subsets of the data (including naturally occurring and synthetic chemicals), and we hypothesize and important role in the interpretation of results for increased cell division due to administration of high doses. 2. Methodological issues in the interpretation of animal cancer tests: constraints on the estimation of carcinogenic potency and validity problems associated with using the limited data from bioassays to estimate human risk, reproducibility of results in carcinogenesis bioassays, comparison of lifetable and summary methods of analysis, and summarizing carcinogenic potency when multiple experiments on a chemical are positive. 3. Positivity is compared in bioassays for two closely related species, rats and mice, tested under similar experimental conditions. We assess what information such a comparison can provide about interspecies extrapolation. 4. Rodent carcinogens induce tumors in 35 different target organs. We describe the frequency of chemicals that induce tumors in rats or mice at each target site, and we compare target sites of mutagenic and nonmutagenic rodent carcinogens. 5. A broad perspective on evaluation of possible cancer hazards from rodent carcinogens is given, by ranking 74 human exposures (natural and synthetic) on the HERP indes.     

Industry's efforts: devices and pharmaceuticals

The pharmaceutical industry has been irreversibly affected by the changes occurring in healthcare. Despite the obvious contributions of pharmaceuticals to human health, our customers are demanding that we help the patient and contribute to value, whether it be in terms of cost, clinical outcomes, or quality of life. We are learning to balance the variables to ensure that cost plus quality equals value in the marketplace in three ways: by focusing on the needs of the customers and demonstrating value through outcomes research, by maintaining an emphasis on innovation, and by taking an active role in the public arena to direct the course of our future. Outcomes research proves the value of what we do. Economic data will have to be correlated with clinical data. In addition to standard clinical and economic parameters, we must also provide quality of life data. Collaboration between the academic and the practicing community produces a win-win situation for both parties. Industry and practitioners are bonded together ineluctably in the service of the patient. Working together we can shape our future and the future of our patients.     

Public health surveillance for hereditary hemochromatosis

The recent realization that hemochromatosis is a common condition has created opportunities to develop unified public health surveillance for this disorder and its complications and to design programs to prevent unnecessary illness and death resulting from this disorder. Public health surveillance for hemochromatosis can be used to measure the magnitude of the problem (for example, to establish the number of persons with evidence of early iron overload); identify research needs; reveal the natural history of the disease; detect changes in health care practices, such as use of screening tests; and evaluate interventions, such as phlebotomy. Existing surveillance has been limited to periodic measurement of morbidity and mortality done by using hospital discharge records, health examination surveys, vital statistics, and data from small research registries. The improvement of surveillance will entail the ongoing collection of information from population-based surveys, such as the Behavioral Risk Factor Surveillance System; the collection of data on provider practices (for example, through the National Ambulatory Medical Care Survey); and the establishment of population-based registries. Creating population-based registries requires consensus on case definitions; strategies to encourage case ascertainment and reporting; policies and procedures for protecting privacy and ensuring confidentiality; and partnerships among providers, researchers, and public health officials. Longitudinal data from population-based registries will provide insight into determinants of disease expression, such as pattern or degree of iron overload. This information is critical for developing evidence-based recommendations for population screening, monitoring changes in medical practices, and assessing the effect of preventive measures.     

Potential contribution of screening to cancer mortality reduction

The objective of screening for cancer is to reduce mortality or to improve quality of life. Screening is practiced for several anatomical sites and by several tests. Only cervical cancer screening based on cytological smears has been shown to be effective as a public health policy. Screening for breast cancer based on mammography was shown to reduce mortality in several randomized trials and nonexperimental studies. However, no data are available on its effectiveness at population levels in terms of a public health policy. There are several other valid tests. Application of these tests has failed to demonstrate a reduction in mortality or such an application was never tried and tested. This emphasizes that the prerequisite for effective screening is that the total program is valid and not only the test. At present, knowledge on screening is not fully applied in most European countries. Regular screening for cervical cancer will result in a 90% reduction in the risk of invasive disease. It is likely that the protective effect for breast cancer is about 30%. At the population level, smaller protections are to be expected, and well-organized screening programs are likely to reduce the total cancer death rate by 6 to 10% among females.     

Congress looks at science.

Congress "has been inviting the nation's top scientists… to come to the witness table… . Congress is not trying to crack down on science; rather it is trying… to equip itself for its constitutional role in an area where it has heretofore been rather laggard." The "Federal Government has been extremely generous to science." Science "has become terribly expensive in recent years… . Congress is beginning to demand, in effect, that the scientific community vouch for it productivity… . Congress is aware of its own inadequacy, which is why the scientific community should be pleased, rather than distressed, by the sudden rush of investigations and studies. They present a splendid opportunity for the nation's scientists to help the political process adopt itself to the needs of science." (PsycINFO Database Record (c) 2010 APA, all rights reserved)