DRUGS

Drugs are notoriously difficult to define and yet present some of the most difficult ethical issues for the science and technology on which they are based. At the simplest level, drugs are molecules whose biochemical effects have been classified as socially desirable or undesirable in different times and places. Dorland's Medical Dictionary defines a drug as a "chemical compound that may be used on or administered to humans or animals as an aid in the diagnosis, treatment, or prevention of disease or other abnormal condition, for relief of pain or suffering, or to control or improve any physiologic or pathologic condition" (p. 510). But this ignores so-called recreational drugs, which may be described as substances used mainly for their psychoactive properties and pleasurable effects.

Historically drugs have been derived from plants and other natural materials and thus their production relied on indigeneous forms of knowledge and premodern techniques, often appropriated for modern applications. Over half of drugs in clinical use today continue to be derived from natural sources—including the excretions of insects, animal organisms, or microbes—from which they are extracted through direct or indirect processes (Aldridge 1998). The other half is synthesized through chemical processes that are now industrialized.

International Regulation

Ethical issues relating to human exploitation of indigenous knowledge and resources—sometimes called bio-prospecting—became central with the rise of a multinational pharmaceutical industry in the mid- to late-twentieth century. International treaties now provide safeguards that guarantee countries sovereign right over their genetic resources and a share of pharmaceutical profits derived from them. Yet such treaties also make national drug policy inflexible, inhibit innovation, and do not necessarily guarantee that indigenous groups that provide genetic materials are fairly compensated.

Given the high profit margins and relatively recession-proof nature of the pharmaceutical industry, drug production, marketing, distribution, and consumption are tightly regulated through a complex series of legal protocols and social controls that start from a set of international treaties that are coordinated through the United Nations Single Convention (1961), still the foundational document of international drug control (McAllister 2000). Prior to 1961 nine separate international treaties governed illicit or addictive drugs, primarily narcotics (opium and its derivatives), coca and its derivatives, and marijuana/hashish. The Single Convention defined the boundary between licit and illicit drugs, as well as legitimate medical and illegitimate, nonmedical, or recreational use, granting expert committees of the World Health Organization (WHO) authority for adding or altering drug schedules, which define how strictly drugs are regulated according to the level of their abuse liability. The Single Convention also mandated that national governments create and maintain drug-control agencies, and otherwise required signers to conform their domestic drug policies to its international mandate.

Regulation in the United States

Regulatory regimes are divided in the United States between illicit drugs, regulated by the Federal Bureau of Narcotics (FBN), the Treasury Department unit responsible for enforcing the Volstead Act (alcohol prohibition) and the Harrison Act, which transmuted into the Drug Enforcement Administration (DEA) in 1973; and licit drugs, regulated by the Food and Drug Administration (FDA) following the Food, Drug, and Cosmetic Act (1938). The 1938 Act granted the FDA authority to designate which drugs would be available only with a physician's prescription (Swann 1988). The liberalization of prescription laws in the 1960s and 1970s culminated in direct-to-consumer (DTC) advertising briefly becoming legal in the United States in the early 1980s prior to an FDA-imposed moratorium finally lifted in 1997. Supranational organizations such as the European Union have limited the spread of direct-to-consumer advertising (DTC) of prescription drugs. New Zealand is currently the only other country besides the United States that allows DTC, although it is under consideration elsewhere.

Well into the twentieth century, proprietary medicines were unregulated in terms of production, advertising, marketing, or distribution. Heavy advertising of commercial compounds emerged in the mid-nineteenth century United States, as patent medicine manufacturers were among the first to market their products nationally. Total advertising expenditures for proprietary medicines soon exceeded those of all other products combined; it was not unusual for nineteenth-century advertising budgets to exceed $100,000 per year, and some reached the million-dollar mark.

Narcotic drugs were restricted to prescription by the Harrison Act (1914), an outcome of growing international concern about widespread use and abuse of opiates, which were one of the few effective drugs then considered part of the medical armamentarium. An ongoing search for a non-addicting analgesic mounted by the National Research Committee propelled early-twentieth century innovation in the U.S. pharmaceutical industry in the context of concerns about addiction liability (Acker 2002). Addiction remains a classically public problem to which a coordinated federal response is understood as necessary, despite disagreement over the form that it should take. The United States remains the largest consumer of illicit drugs and has continued to struggle against what has proven a largely intractable problem. Basic research efforts into the neurobiochemistry of addiction led to the visualization of multiple opiate receptors, long hypothesized to exist, in the early 1970s. Federally funded studies of drug addiction have shifted away from the social and health consequences of abuse, and toward the use of molecular and animal models in establishing the basic neurobiological and now biogenetic mechanisms of drug action.

Drug Evaluation

Classified according to what is known about their mechanism of action, as well as their predominant effects on human and animal populations, both prescription and over-the-counter drugs must now be evaluated for safety, efficacy, abuse liability, and therapeutic effects. First their metabolic effects must be determined in animal models. Clinical trials in healthy human volunteers take place after pharmacokinetic studies in animals. Trials are divided into four phases, three of which take place before licensing and one of which occurs once patients are prescribed the drug by participating physicians. The large-scale clinical trials system in place in the United States since the 1960s is complex, lengthy, and expensive. Both the FDA and the National Institutes of Health (NIH) reluctantly became involved in regulating and coordinating the testing and licensure system for new drugs (Hertzman and Feltner 1997). Ethical concerns relevant to clinical trials include determinations of the capacity for informed consent of experimental human subjects; balancing rights to privacy and confidentiality with public access to information; the design and execution of double-blind, placebo-controlled studies; and how to go about occasionally halting a trial as adverse effects become clear.

Ethical questions are raised both in terms of the type of drug development, production, marketing, and distribution being promoted; and the conditions of use. Drugs play a different role depending upon whether they are administered within allopathic or homeopathic therapeutic regimes. Homeopathy involves the administration of minute dosages of drugs designed to produce symptoms in healthy persons that mimic the symptoms of the disease for which the person is being treated. Developed by Samuel Hahnemann (1755–1843), homeopathy has been the target of many conflicting claims concerning its safety and efficacy in the face of the dominant practice in western medicine, allopathic treatment, which seeks to produce conditions that are incompatible or antagonistic to the disease. Many aspects of complementary and alternative medicine (CAM) are now being explored through large-scale clinical trials, since tremendously high percentages of U.S. patients now seek alternative practitioners in conjunction with allopathic practitioners, leading to a vast and less regulated market for so-called nutraceuticals, off-label use of pharmaceutical drugs, and herbal remedies untested by scientific regimes.

One of the major events in twentieth century history of drugs was the coincidence between the trend toward deinstitutionalization of mental hospitals that began in the 1940s with the psychopharmacological revolution that occurred upon introduction of a major tranquilizer, chlorpromazine (CPZ, marketed as Thorazine in the United States and Largactil in Europe), in the 1950s. This was followed by the first popular use of pep pills (amphetamines) and the mass marketing of minor tranquilizers such as Miltown in the late 1950s, which brought advances in psychopharmacology to popular attention (Smith 1991). Since that time periodic concerns have surfaced as to the social value of drugs used for performance enhancement or marketed widely as lifestyle drugs in ways that have changed the meaning of medical use. Pfizer Pharmaceutical's introduction of Viagra, a drug used to temporarily correct erectile dysfunction and targeted toward relatively affluent male consumers, brought to light disparities in insurance coverage of lifestyle drugs such as the lack of insurance coverage for female contraceptives, whose coverage has been restricted due to the abortion controversy. This Viagra gap illustrates one of the persistently troubling ethical issues in the domain of drugs, namely that of research and development targeted toward developing or widening markets among the affluent through lifestyle or look-alike drugs that are simply a means for drug companies to gain market share, compared to the relative lack of attention to drugs for treating orphan diseases that seriously affect small numbers of individuals, or those diseases—such as malaria or schistosomiasis—that mainly affect individuals in the developing world.

While the FDA is often regarded as an agency that largely serves the needs of the pharmaceutical industry, three major reproductive health controversies of the 1960s and 1970s propelled the FDA into taking a somewhat proactive regulatory role. These were the development of hormonal methods of contraception; widespread prescription of Thalidomide to pregnant women in Europe, while the drug was still experimental in the United States when it was demonstrated to cause severe birth defects; and prescription of diethylstilbestrol (DES), which caused in utero defects and increased rates of cancer in the children of women who took it. These controversies arose simultaneously with interrelated social movements that targeted health and physician-patient relationships, including the patients' rights movement, the consumer rights movement, the women's health movement, and, later, the HIV/AIDS movement. These social movements sought to limit the use of certain classes of therapies such as electroshock (ECT) and drugs such as the major tranquilizers or benzodiazepines (Valium) among certain populations. They also agitated for increased inclusion in clinical trials, earlier and more democratic access to experimental drugs, and expanded patients' rights including privacy, confidentiality, and informed consent.

Pharmacogenomics

Pharmacogenomics is the attempt to identify individual, genetic variation in drug response—metabolism, transport, and receptors—and to extend those findings to population genetics through a variety of information and visualization technologies. Pharmacogenomics promises individually tailored medications that would likely decrease adverse drug reactions, currently the fourth leading cause of death in the United States.

Projects in this research arena raise novel ethical and legal issues related to the creation of sample repositories or banks of genetic materials that would enable hypothesis-driven research on statistically significant differences in the phenotypes of human subjects. Such research could help establish the safety, efficacy, and compatibility of certain classes of drugs for particular individuals or populations; and could be used to create a complex set of biomarkers that describe the particular complement of different neuroreceptors that an individual has that may make him or her more or less responsive to a range of addictive substances (tobacco, opiates, and others) or prescribed medications. Pharmacogenetic databanking is potentially useful for avoiding adverse consequences but could also create a rationale for genetic and health-related discrimination. As with previous advances in the field of pharmacology, pharmacogenetics presents a double-edged sword, and its meaning and ethical value will be determined by the social contexts in which it is deployed.

NANCY D. CAMPBELL

SEE ALSO Bioethics;Clinical Trials;Complementary and Alternative Medicine;DES (Diethylstilbestrol) Children;Food and Drug Regulatory Agencies;HIV/AIDS;Medical Ethics;Sports.

BIBLIOGRAPHY

Acker, Caroline. (2002). Creating the American Junkie: Addiction Research in the Classic Era of Narcotic Control. Baltimore, MD: Johns Hopkins University Press. Thorough historical study of addiction research up to the 1940s, including the ongoing search for a non-addicting analgesic.

Aldridge, Susan. (1998). Magic Molecules: How Drugs Work. Cambridge, England: Cambridge University Press. Highly accessible general introduction to drugs.

Balance, Robert, Janos Pogany, and Helmut Forstner. (1992). The World's Pharmaceutical Industries. Brookfield, VT: Edward Elgar.

Campbell, Nancy D. (2000). Using Women: Gender, Drug Policy, and Social Justice. New York: Routledge. Social and cultural history of the representation of different populations of women who have used illicit drugs in the twentieth-century United States.

Courtwright, David T. (2001). Dark Paradise: A History of Opiate Addiction in America, enlarged edition. Cambridge, MA: Harvard University Press. Classic historical demography on opiate addiction in the United States.

Cozzens, Susan E. (1989). Social Control and Multiple Discovery in Science: The Opiate Receptor Case. Albany: State University of New York Press.

Dorland's Medical Dictionary. 1980. Philadelphia: Saunders Press.

Healy, David. (2002). The Creation of Psychopharmacology. Cambridge, MA: Harvard University Press.

Hertzman, Marc, M.D., and Douglas E. R. Feltner, M.D. (1997). The Handbook of Psychopharmacology Trials: An Overview of Scientific, Political, and Ethical Concerns. New York: New York University Press.

Liebenau, Jonathan, Gregory J. Higby, and Elaine C. Stroud, eds. (1990). Pill Peddlers: Essays on the History of thePharmaceutical Industry. Madison, WI: American Institute of the History of Pharmacy.

McAllister, William B. (2000). Drug Diplomacy in the Twentieth Century. New York: Routledge. Detailed diplomatic history of the global regulation of drugs.

Musto, David F. (1999). The American Disease: Origins of Narcotic Control Policy, 3rd edition. New York: Oxford University Press. Foundational text in the field of drug policy history.

Smith, Mickey C. (1991). A Social History of the Minor Tranquilizers. New York: Haworth Press.

Swann, John P. (1988). Academic Scientists and the Pharmaceutical Industry: Cooperative Research in Twentieth-century America. Baltimore, MD: Johns Hopkins University Press.

Terry, Charles, and Mildred Pellens. (1970 [1928]). The Opium Problem. New York: Bureau of Social Hygiene. Reprinted by special arrangement with The American Social Health Association, Montclair, NJ: Patterson Smith. Fascinating compendium of over 4,000 nineteenth- and early twentieth-century studies on the effects of opiates.

White, William L. (1998). Slaying the Dragon: The History of Addiction Treatment and Recovery in America. Bloomington, IL: Lighthouse Institute. The best of very few historical works on drug treatment regimens.