When the results of biological research suggest links to the practice of medicine or public health, we enter a realm somewhere between science and technology (/). Call it basic or fundamental research, its name matters less than the difficult problems it brings to the fore. The most important of these is the question of practical application. In this issue of the Journal, Brandes et al. (2) report mixed effects of prescribed and overthe-counter antihistamines on the growth of tumors in mice. What, if anything, should be done? History teaches that, when faced with this question, sometimes it is better to wait and other times it is better to act quickly. In this particular instance, the best answer is to wait. How we arrived at that decision may prove helpful for those in the future who find themselves between science and technology. At their core, these decisions are not just complex, they are downright daedalian. Part science, part ethics, often politicized, they require knowledge from different sources with different characteristics. Consider scientific knowledge. It is a hierarchical structure, ranging from the molecular intricacies of intracellular regulatory systems to the population mortality experience of men and women of many cultures (3). Ever-growing, multilayered, and almost unfathomable, it spans many disciplines. We familiarize ourselves with large segments of it and race to produce new findings, sometimes linking one level with another. Despite our best efforts, the structure of scientific knowledge remains incomplete (4). Ethics is also important. Its hierarchical structure is composed of theories, principles, rules, and cases. Much older than science, ethics is also woven from a different fabric. Less emphasis is placed on observation, more is placed on theory, yet in the end, ethics is eminently practical. The structure of ethical knowledge, along with the methods of reasoning developed to traverse it, helps us to decide the right thing to do. We need both structures for effective decision-making: science because we seek the truth and ethics because we seek the good. No algorithm exists for these decisions, just as no statistic neatly connects the levels of scientific explanation, and no method of reasoning connects the structures of science and ethics. Yet the decisions are there, and we in the health professions are obliged to make them. In an effort to keep the problem manageable, we limit the focus to the particulars and invoke two concepts: evidence (5) and the principle of beneficence (6). The circumstances are these: Two tumor culture lines, when injected into mice and then treated with human-equivalent doses of three compounds with antihistaminic properties (loratadine, astemizole, and hydroxyzine), grew heavier than those same lines unexposed to the compounds. When exposed to two other antihistamines (doxylamine and cetirizine), the tumor wet weights were either no different or less than those of the unexposed. Ranked scores for these compounds on a battery of in vitro tests predicted tumor growth properties. The authors of the report (2) suggest that the experiments be repeated with different tumor lines and in models using chemical carcinogens or human tumors transplanted into nude mice. They also recommend epidemiologic studies. We concur. Analytic epidemiologic studies to better characterize the potential effects of exposures on human tumor growth, perhaps using serial measurements of biomarkers or results of screening tests, could provide important information. Should anything else be done? After all, four of the five antihistamines are available in U.S. pharmacies. Hydroxyzine, for example, is commonly used in the treatment of anxiety and pain in many conditions, including cancer (7); it is also used in combination with synthetic opiates for the treatment of preoperative and postoperative pain. Doxylamine is an ingredient in over-thecounter cold preparations. The circumstances invite consideration of the human relevance of rodent evidence. This issue has been argued for at least two centuries (5), and the keys to the kingdom lie embedded within the complexities of the ever-incomplete structure of scientific knowledge. Although we have learned much from rodent models, it is difficult to assess transferability of specific results. Human tumors and systemic exposure to antihistamines unquestionably arise from conditions markedly different from those experienced by mice in the laboratory. On the other hand, many species possess intracellular histamine receptors, the path-
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Jul 25, 2014
Tanuja Gandhi + 1
Open Access