Society's Choices: Social and Ethical Decision Making in Biomedicine (1995)

During the past 30 years, the study of ethical issues in the life sciences has become a public concern, debated in the press and, increasingly, guided by governmental commissions, professional societies, and community organizations. The issues have sometimes demanded public attention, as have cases of the abuse of human research subjects, and, at other times, more gradually raised public concern, as have the possibilities provided by advances in genetic technology. More and more, the ethical implications of such issues as health care delivery and commercialization of biotechnology are being pursued in a public fashion. The recent Clinton administration task force on health care reform involved ethicists as consultants; the ethical aspects of academic-industry relationships in the biotechnology industry was the subject of recent congressional hearings. Despite the increasing activity in this area, however, there has been little systematic study of the various collective processes through which we subject these ethical and social issues to debate and analysis. In an attempt to delineate the elements of these processes as they are practiced in this country, the committee found it useful to define more clearly one of the central notions of this discussion-namely, ethical issues or dilemmas.

The word "ethical" is often used interchangeably with the word "moral," although both words also have narrower and more specific meanings (e.g., "ethical" may refer to an issue such as conflict of interest in political set-

tings; "moral" may refer to an issue such as sexual conduct as well as very broad and undefined meanings referring to human values in general). It is difficult, perhaps impossible, to define precisely what these words mean. Often the definitions one finds in the ethics literature define ethics and morality in terms of values, moral principles, virtues, and the like, terms that are in turn defined in terms of ethics and morality. Even if we assume that we share a common, intuitive understanding of these terms, moreover, it is not clear how we come to view a given issue or question as an ethical one. For example, cloning a human being is viewed as an ethical issue whereas international trade agreements typically are not-even though both involve moral choices and affect the vital interests of Americans.

Nearly every public issue requires moral judgments in its resolution. These judgments may be visible or invisible, explicit or implicit, addressed as such or ignored. Thus it is not particularly helpful to decide which public issues are inherently "ethical." However, we can usefully distinguish between issues that are discussed and resolved with reference to the ethical questions they pose and issues debated on other grounds. The former are those discussed in terms of moral ideas, such as dignity, freedom, rights, fairness, respect, equality, solidarity, responsibility, justice, and integrity. Some of these are personal virtues, others are features of social life; some are powers, others ideals. What they have in common is that they are mentioned when one tries to speak of right and wrong, and that they are invoked in discussions that go beyond assertions about facts and descriptions of events to claims about why things ought to be done in certain ways or what ought to be done.

Perhaps there exist (or once existed) societies in which a single code of morality is so universal and so comprehensive that its members know right from wrong in every situation without need of debate and deliberation. Ours is certainly not such a society. Americans often disagree about standards of justice, conceptions of fairness, and the requirements of integrity; and even when they agree they may still not apply these concepts in the same way to a given subject. Moreover, they may disagree over the facts of the case to which moral standards are to be applied. The discussions and debates that ensue are "ethics" discussions and debates. They form an important subset of the social choices that we routinely confront.

Some "ethical issues" consist in deciding how to react to a moral outrage or scandal. In these cases there is virtual unanimity on the wrongness of what has occurred and no moral argument is needed. Other "ethical issues," however, represent genuine quandaries. With these issues the answers are unclear; they provoke moral disagreement, whether between people or in the form of ambivalence or uncertainty in the mind of individuals. The creation of the Ethical, Legal, and Social Implications (ELSI) Program of the Human Genome Project, for example, was stimulated by

genuine uncertainty about the possibilities brought about by new capabilities in genetics. While some perceived new genetic technologies to be encroaching on sacred territory-our identity as humans-many others focused on the potential of these same developments to end suffering from gene-linked diseases and disabilities.

People who disagree over ethical issues can attempt to ignore their differences or to outflank or overpower their opponents. Or they can seek to expand their understanding and perhaps reach agreement or compromise through open discussion and rational moral deliberation, investigation, and argument. This is the potential role of bioethics debates, whether undertaken between neighbors concerned over a personal experience in medicine, or between clinicians perplexed by the moral dimensions of a case, or among presidential appointees to a bioethics commission.

One hallmark of moral deliberation is its ideal of impartiality. Ethical deliberation should be distinct from the pursuit of self-interest; it should also be different from advocacy. Each person, when he or she takes the moral point of view, is supposed to put aside self-interest and the emotions of the moment. Though our cultural, psychological, and religious differences may create some barriers to common agreement, each of us expects the considerations and arguments that lead us to our positions on moral issues to be plausible to other reasonable people who deliberate on these same issues. For example, when we oppose experiments on unconsenting human subjects, we argue that the subjects' right of self-determination is violated, and we expect others to agree that these rights exist. If not, we marshall arguments in support of that proposition, and again appeal to considerations that we expect to be persuasive to those who disagree with us. There is no guarantee that unanimity will be reached, nor even that any consensus that emerges will be well advised and without error. Yet there is widespread agreement on the rules of procedure in ethical argument. Few would be persuaded by a person who backed up a claim about right and wrong by an appeal to personal tastes, feelings, or preferences, for none of these have the essential quality of impartiality.

Our society's capacity for dealing humanely and wisely with the impact of technological and scientific innovation is enhanced by the creation of forums in which this kind of impartial deliberation can be carried out. This deliberation may draw on many resources: actual experience in the use of these technologies and in the practice of medicine; the personal values and life experiences of participants; bodies of formal analysis, such as economics and the law, which reflect and systematize moral judgments; and, not least, the intellectual and scholarly resources of the field of ethics. This report emphasizes the wide variety of settings in which these deliberations are occurring and the diversity of intellectual resources that can be brought to bear on public moral discourse.

The tasks of ethics bodies convened to address issues in biomedicine have originated from clashes of values, norms, principles, and practices that have occurred in a number of arenas, especially: biomedical research involving human subjects; health care decision making, delivery, and financing; advances in medical diagnostics and therapeutics; and academic industry relationships in biotechnology. From these spheres have come new technologies, the proper use of which is controversial; allocation crises and perplexing questions of distributive justice; changes in the organization and delivery of health care and concerns about the appropriate role of physicians; and financial and policy incentives that have spawned new relationships of questionable appropriateness between researchers and their sponsors. It was in the sphere of human studies research that the ethical dimensions of biomedicine and the need for public involvement in defining these dimensions was first recognized.

The use of human beings as research subjects has ancient roots. The Hippocratic tradition recognizes the uncertainty of medical practice. In the famous Hippocratic aphorism, "Life is short, the art long, experience fleeting, experiment perilous,judgment uncertain," there is an awareness that innovative practice carries dangers. Yet no explicit discussion of the ethical dimension of experimental medicine is found in this literature; little more is found in the literature of subsequent centuries.

Specific attention to this issue flowered in the mid-nineteenth century through the work of Claude Bernard, who introduced techniques for comparing different treatment methods. In An Introduction to the Study of Experimental Medicine (1865), Bernard declared:

This linkage of practice and science became crucial in the early twentieth century as medical innovations made possible the noninvasive monitoring of human functions. Inventions such as the blood pressure cuff, electrocardiograph, X-ray, and blood chemistry using small quantities of blood,

allowed scientists to monitor physiological functions without the required invasive techniques that previously dictated the use of animals. Also, mathematical models and statistical techniques made possible discriminating analysis of differences between treatments. In the 1920s and 1930s, it was seen as appropriate for patient care to become a venue of scientific teaming, and for the line between treatment and experimentation to be erased. At that time, Alfred Schwitalla, regent of the medical school at St. Louis University, wrote: "The sick human being, it is true, is not a laboratory animal, but neither is he so isolated in his human glory that he must consider himself outside the possibilities of some, carefully controlled, watchfully supervised experimentation" (Schwitalla, 1929).

The need to assert a clear distinction between practice and research became apparent at the end of World War II. The heinous experiments carried out during the war led to the enunciation of ethical standards that proscribed scientific zealotry and the desire for social benefit at the expense of human consent and dignity. The Nuremberg Code of 1948 is probably the most widely recognized of such declarations. Designed as a standard by which to judge the actions of the perpetrators of the wartime experiments, including the physicians involved, the code filled an important void in the existing medical standards.

Consent of the subject is the linchpin of the Nuremberg Code. The first principle of the code states: "The voluntary consent of the human subject is absolutely essential" (Nuremberg Code, 1949). The code's ten principles establish a wall of protection for the subject and place independent responsibility for avoiding harm to the subject on the shoulders of investigators. The ethical principles enunciated in the Nuremberg Code remain important guides for human experimentation today.

The Nuremberg Code stimulated additional influential statements on the ethical use of human subjects in research. One such statement was issued in 1953 by the Clinical Center at NIH. Titled "Group Considerations for Clinical Research Procedures Deviating from Accepted Medical Practice or Involving Universal Hazards," these were the first federal guidelines for human studies research and the first official statement requiring committee review of human studies protocols.

The Declaration of Helsinki, adopted in 1964 by the 18th World Medical Assembly in Helsinki, Finland, was another such statement. The declaration specified that experimental protocols for clinical research should be sent to a "specially appointed committee for consideration, comment, and guidance," making it the first international research guideline to address the concept of independent review (Levine, 1986). The Declaration of Helsinki included no mechanisms for enforcement of its guidelines, however, except for a recommendation that the results of research not complying with the declaration be rejected for publication. The ultimate duty to

serve as protector of human subjects of biomedical research remained the physician's.

Many observers assumed that these proclamations would be sufficient to assure ethical behavior by physician investigators, but revelations in the 1960s of further abuses of human subjects made it clear that this was not true. In 1966 came the news that researchers at the Brooklyn Jewish Chronic Disease Hospital had injected live cancer cells under the skin of elderly patients to test immune competence. The patients had not given, and in some cases could not give, adequate consent to participate in the investigation.

Also in 1966, physician Henry Beecher gave a lecture (and later wrote an article) that presented 22 research studies in which there were serious problems related to the use of vulnerable, disadvantaged, and unaware human subjects. In some of the studies the risks were not adequately explained to the subjects; in others, subjects were not even made aware that they were participating in an experiment. Beecher concluded, "It must be apparent that they would not have been available if they had been truly aware of the uses that would be made of them" (Beecher, 1966).

The controversy stimulated by these and other revelations led to a 1966 surgeon general's ruling that required all medical institutions funded by the Public Health Service to empanel human studies committees made up of scientists, clinicians, and lay members of the community. These committees had two major functions: (1) to evaluate whether the consent form to be signed by subjects was complete and clear; and (2) to decide whether the experiment could be conducted in a manner safer for the subjects, or whether it was safe enough to be conducted at all. Human studies committees declared by their presence that biomedical research was a public enterprise, and that members of the public had important views to offer about its ethical dimensions. The tasks of human study committees later became further refined with the promulgation of federal guidelines. In 1971, the Department of Health, Education, and Welfare (DHEW) issued a publication entitled "Institutional Guide to the DHEW Policy on Protection of Human Subjects," which contained detailed considerations of institutional review and informed consent requirements.

While the creation of research review committees raised public and investigator consciousness about the ethical dimensions of biomedical research, the revelation in 1972 of the Tuskegee Syphilis Study, an observational study of untreated syphilis in black men, begun in 1932, revealed the need for even clearer guidelines and more forceful measures for compliance. A now-infamous litany of ethical abuses characterized the study: no informed consent was obtained from the participants, the men were steered away from treatment even after the discovery in the 1940s that penicillin could effectively treat the disease, and they were deceived into believing

that they were receiving treatment when they were not. Congress convened an independent panel that concluded that the Tuskegee Study was highly unethical and should be immediately halted. The panel also declared the protection of human subjects to be a widespread problem and expressed concern that no uniform policy existed for the protection of human subjects of federally funded biomedical research. Among other recommendations, the Tuskegee panel advocated the strengthening of guidelines regarding the review of research protocols by independent committees. These recommendations were reflected in formal policies promulgated in 1971 in the DHEW publication entitled "Institutional Guide to the DHEW Policy on Protection of Human Subjects," mentioned above.

In 1973, the Senate Committee on Labor and Public Welfare held a series of hearings regarding human experimentation that included discussion of such issues as research on human fetuses, sterilization of the mentally retarded, and use of prisoners (Senate Committee on Labor and Public Welfare, 1973). The hearings received extensive television coverage and further increased public awareness of and concern about ethical problems in biomedical research. There was considerable public outrage over reports of fetal research, particularly over a research project that had been conducted in Finland using the perfused heads of aborted fetuses. This study, together with the Tuskegee study, was the stimulus for congressional action on research ethics in the form of the National Research Act of 1974 (P.L. 93-348).

The National Research Act established The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (see Chapter 4 for more information on this commission). The National Commission was charged to identify ethical principles that would guide research on human subjects and to develop relevant guidelines for researchers and institutions. The Act also formally established the requirement that research institutions must have an institutional review board (IRB) as a mechanism for the protection of human research subjects (see Chapter 3 for more information on IRBs).

Thus, during the 1970s and 1980s, serious efforts were made to distinguish biomedical research from medical practice. The inherent possibility of conflict between benefit to the patient and benefit to knowledge and society has been acknowledged, and, groups like IRBs and commissions have been entrusted to help investigators, research subjects, and society decide how best to judge the trade-offs.

Recently, President Clinton appointed a 15-member Advisory Committee on Human Radiation Experiments to provide advice and recommendations on the ethical and scientific standards applicable to human radiation experiments carried out or sponsored by the United States government between 1946 and 1974. The group has been charged with reviewing

several specific experiments about which questions have been raised concerning whether subjects were treated properly. Composed of experts in medicine, science, ethics, and law, the advisory committee will submit its report in 1995. The rapid establishment of the advisory committee in response to reports of potential past abuses demonstrates the capacity of the federal government to respond to ethical issues.

The seed that was planted in the public consciousness by abuses of human research subjects would later sprout in other areas. The doctrine of informed consent, central to the ethics of clinical research, was at the heart of the movement in the 1960s and 1970s toward greater patient autonomy. At the same time, medical technology began to flourish and health care began its transformation into the business-like enterprise it is today. The resulting specialization, fragmentation, and depersonalization of health care became sources of social and ethical quandaries of great concern to individuals and the public.

Revelations that persons had been subjected to medical experimentation without their knowledge or consent led to great concern that similar situations not occur in the context of medical practice. This concern was directed not only at the potential for the recurrence of blatant abuse, but also at routine questions of disclosure and decisional authority. The newfound interest in greater patient autonomy posed a serious challenge to the historical authority of physicians, who had previously seen patient participation in medical decision making as largely discretionary. Joseph Fletcher's pioneering Morals and Medicine (1954) had urged physicians to afford patients freedom of choice and ''the fullest possible knowledge" of the medical facts and available alternatives, but the true focus of Fletcher's book was on the dying patient's "right to know the truth" (Faden and Beauchamp, 1986). Physicians continued to consider it their professional responsibility to make treatment decisions for patients, and even to employ what has been called "benevolent deception" when communicating with patients. An excellent account of the history of ethics in medical decision making can be found in David Rothman's Strangers at the Bedside (1991).

A cluster of legal cases in 1972 explored the issue of disclosure of information by physicians to their patients and the implications of this disclosure for patient self-determination. While traditional practice standards had permitted professional discretion to dictate what physicians told patients, Canterbury v. Spence, Cobbs v. Grant, and Wilkinson v. Vesey chal-

lenged these standards, claiming that even when a medical procedure is skillfully performed, physicians may nevertheless be liable for adverse consequences about which the patient was not adequately informed. The decisions in these cases combined features of negligence and battery theories into a new approach to informed consent in the medical setting that attempted a fairer balance between patients' rights to self-determination and the demands and complexities of both the physician-patient relationship and the legal setting (Faden and Beauchamp, 1986). Partly as a result of these decisions, the traditional model of medical practice, characterized by paternalism and authoritarianism, eventually gave way to a new model of informed consent, where the competent patient's decision-making authority became primary.

Ironically, the triumph of patient autonomy raised a new set of ethical quandaries. Many clinicians fear that strict observance of patient autonomy may override good medical judgment, encourage moral detachment on the part of the physician, and even work against the patient's best interests (Brock, 1991; Pellegrino, 1993). Patient autonomy also raises questions about increased public costs for expensive but not necessarily beneficial technologies, as well as about prolonging the quantity of life at the expense of quality of life. Empirical research in this area would enhance our understanding of the attendant ethical quandaries.

In addition to the changes in patient care engendered by a new emphasis on patient autonomy, the continuing technological revolution in medical diagnosis and treatment has further altered the delivery of health care and the relationship between patient and provider. Where the physician had once been viewed as omniscient, new medical technologies demythologized the individual physician's role. People began to view physicians less as personal therapeutic forces than as accomplished wielders of technology.

Coincident with the growth of new medical technologies has been an increase in specialization in the health establishment and the proliferation of health care delivery "teams" to administer specialized care. It is not always the physician who leads the team or has the initial or greatest contact with the patient or client. For example, health maintenance organizations (HMOs) might assign a nurse practitioner or physician assistant as a primary care provider or gatekeeper to specialized care, instead of a family physician. A cardiac surgeon may lead both the preoperative and operative teams, while a cardiologist and a cardiac nurse intensivist might lead the postoperative aspects of care. All of these caregivers share in the responsibilities for care of a patient, but each may be distant from total accountability for the patient's welfare.

This arrangement has contributed to a sense of isolation on the part of the patient. Sometimes, it seems that no one is in charge; that no one is

there to take overall responsibility; that everyone can, with some justification, feel that almost anything should be taken care of by someone else on the extended team. Advanced technology and the increasingly complex organizational styles it has engendered tend to isolate patients as human beings at just the time when and in the settings where their confrontation with suffering and death may be most intense. The impersonal tone of medical care and the surge in the medical expert industry spurred a growing discontent among patients as health care consumers (Reiser, 1993).

These developments, along with physician paternalism, set the stage for the emergence of a distinct patient rights movement in the early 1970s, a movement that primarily addressed patient rights in hospital care. In 1970, several consumer groups successfully petitioned the Joint Commission on the Accreditation of Hospitals (JCAH) to redraft its standards to address patients' concerns. In 1973, the American Hospital Association published the Patient Bill of Rights, the first explicit statement of the rights of patients and the responsibilities of physicians and medical institutions. Considered by many to be a landmark in the quest for patient autonomy, the bill acknowledged patients' rights to complete and current information in terms that they can understand, to informed consent prior to treatment, to refusal of treatment, and to be advised of and refuse to participate in experimental treatments (American Hospital Association, 1973).

Other developments in the 1970s and 1980s further facilitated a growing acceptance of patient autonomy as the hallmark in both clinical decision making and research. The National Commission's Belmont Report (1978) emphasized the need for informed consent and protections for research patients in research trials. The commission's work on informed consent was later continued and applied more to the clinical treatment context by the President's Commission, two of whose reports dealt specifically with the patient's right to informed consent and with the right to refuse life-sustaining treatment (President's Commission, 1982, 1983).

In the last decade, the rights and concerns of patients have held a central place in ethical and health policy discourse. Patient advocates are now employed in many hospitals. State court decisions concerning the right to refuse medical treatment have continued, culminating with a Supreme Court decision recognizing a competent refusal of treatment as a constitutionally protected liberty (Cruzan v. Director, Missouri Department of Health, 1990). Physician-assisted suicide and euthanasia continue to stir divisive national debate. The recent focus on outcomes research, and calls for increased participation of consumer consultants and advocates in health-care decision making and policy, are just a few examples of a growing trend to involve patient consumers in all levels of health care policy (Reiser, 1993). Finally, the national debate on health care reform has focused significant attention on patient concerns and needs.

Over the past 50 years, the structure and financing of health care has changed in many ways: medical care once rendered by a personal physician is now parceled out among many specialists and often takes place in vast, impersonal institutions. Its costs, once paid out of pocket by the patient or even provided gratuitously by the physician, are now paid by insurers or by government. In many respects, these changes are beneficial: specialists may provide more skilled care, institutions may supply more sophisticated technology, insurers may pay what the individual could not. At the same time, these changes pose threats to the features of human life that we have designated as ethical, such as individual rights, dignity, liberty, and fairness.

The American hospital began as a charitable institution for the sick poor and evolved into an institution that, relying on community support, made its facilities available to those who could pay and those who could not on a nonprofit basis. This was accomplished by philanthropy and the widely accepted practice of cost-shifting, by which those able to pay subsidized those unable to do so. However, by the 1970s, the need to control rising health care costs and pressure from third-party payers to do so forced hospitals to assume an increasingly business-like mentality. One important third-party payer was the government, which administered Medicare. As hospital costs escalated, payers and providers resisted the financial burden of those who could not afford to pay or had inadequate or no insurance. Determinants of hospital economic viability, like occupancy and proper payer mix (i.e., the proper percentage of patients covered by third-party payers), set the stage for concerns about fair access and about conflicts of interest between hospitals' economic health and patients' physical health.

Financial and organizational systems also vary greatly among institutions: some are wealthier than others, resulting in differential availability of care. Sometimes institutions located in the same city, and staffed by the same specialty teams, operate according to widely variant standards of care. For example, a major county hospital in an urban center might offer dialysis to patients only when symptomatic uremia has progressed to a critical stage, because the hospital cannot afford more dialysis capacity. At a major private teaching hospital in the same city, patients may be dialyzed at lower symptomatic levels (perhaps even before they feel ill from renal failure), since reimbursement and private resources allow it.

Insurance companies have adjusted to the changing environment by segmenting the market, leaving more and more of those outside the work force without insurance and health care. Insurers have also attempted to cut costs by excluding innovative, expensive therapies from coverage on the grounds that they are experimental. This means that those with the

means to pay for treatment when an insurance claim is rejected have access to care that is closed to persons who are less affluent. In addition, the practice of denying coverage for treatment of preexisting conditions can severely limit many people's freedom to change employers and can cause enormous out-of-pocket expenses even for those with insurance.

As insurance companies try to manage their risks, so too do physicians. In our increasingly litigious society, malpractice suits against physicians are common place, especially as the personal physician is replaced by the more remote specialist. Operating under the threat of malpractice, physicians sometimes perform procedures that are medically unnecessary or marginal in order to protect themselves from the accusation that they did not do everything possible. Inappropriate use of tests and technology carries its own risks to patient health and raises the overall costs of health care, as do the large amounts of money paid by physicians for malpractice premiums.

Thus, these changes in the structure and financing of health care put persons in need of health care into a system that may ignore their dignity as individuals, impose on them or on society as a whole costs that are unfair, and distribute services in an inequitable fashion.

There are many engines driving technological advance in the biomedical sciences, but it is not entirely clear that maximal stoking of those engines is necessarily the route to equitable distribution of the good that new knowledge can bring. Congressman George Brown, Jr., Chairman of the Committee on Science, Space, and Technology of the U.S. House of Representatives, has argued that the free-market drive to technology, based on the notion of sustained economic growth, may not be the most direct path to improved quality of life for all. He observes, on the contrary, that freewheeling market forces and the drive for high-technology solutions to our society's problems may in fact displace nontechnological, readily distributed preventive solutions in favor of inequitable, expensive, and sometimes even less effective solutions (Brown, 1993). Implied in his argument is the notion that high-technology solutions to biotechnological problems are more likely to produce ethically contorted and difficult situations than are the simpler, low-technology solutions that are driven by concern for the fair and equitable access for all to elemental human needs. Our country's experience with biomedical technology lends some credence to this idea.

During the latter half of the twentieth century, federal investment in research and development has fueled a steady stream of advances in science and technology in general and in biomedicine in particular. The federal government, through NIH, is the principal supporter of biomedical research in U.S. universities and research institutes. But despite the

effectiveness of this massive technological effort in fields from physics to material science, as well as the development of biomedical procedures, there have been increasing calls to examine the potential harm that might flow from advances in science and technology.

The biomedical advance that perhaps most effectively illustrates the sometimes troubling consequences of technology was the development of kidney dialysis techniques to save the lives of patients with terminal renal disease. The technology was effective but expensive, and therefore not universally accessible. In the early 1960s, a kidney dialysis team in Seattle, recognizing that it would not be able to treat all medically deserving patients, established a selection committee to choose patients who would receive the treatment (Jonsen, 1993). The committee came to be called the "God Committee," and the well-publicized pain of its dilemma and its choices was relieved only by the passage of legislation that provided funding for treatment of all kidney patients. This experience served to alert both the general public and the medical community to the problems created by limited resources and the desperate need to anticipate such situations and institute equitable solutions.

More recently, advances in molecular genetics have delivered the promise of both technical benefits and ethical problems. Large collaborative efforts have already succeeded in isolating and characterizing some of the genes responsible for a number of our society's most burdensome genetic disorders, including cystic fibrosis, Huntington's disease, fragile X syndrome, and certain forms of common cancers (breast, colon, and prostate). Population-wide screening tests for these and many more disorders may be within reach. The Human Genome Project, well on the road toward its objective of producing a detailed map of the entire human genome, promises to identify many additional targets for genetic screening tests and gene therapy. Yet, it is likely that social and ethical concerns about employment and insurance discrimination and about the value of knowledge about one's future health will develop in concert.

Recent dramatic changes in the research and development relationships between industry and academia threaten to upset the time-honored traditions of the biomedical sciences. In the past, academic scientists provided a constant stream of basic biomedical research and a cadre of new investigators as a source of renewed talent. Their activities were generously funded by NIH. Industry would center its attention on the development of their ideas into marketable products. Today, however, the process is undergoing radical change as commercial interests seek to direct scientific discovery.

The ethical issues raised by the tendency of universities and government laboratories to establish closer ties with industry through Cooperative Research and Development Agreements (CRADAs) need to be carefully examined. This need is starkly illustrated by a controversial proposed agreement between Sandoz Pharmaceutical Corporation and Scripps Research Institute, which is being renegotiated under pressure from both the NIH and Congress. The agreement would have given Scripps more than $300 million over 10 years, starting in 1997, in exchange for worldwide license to all Scripps medical or manufacturing inventions (excluding existing research agreements). A joint scientific council (with a Sandoz majority in members) would have been able to influence the direction of research by the Scripps scientists. Under the proposed agreement, Sandoz would have reviewed invention disclosures before they could be filed with the government, and even ongoing Scripps research projects could be transferred to Sandoz facilities for further research and development (Anderson, 1993).

A variety of changes in law and science policy have caused scientists to seek such business-related agreements. Although Congress has steadily increased the funding for NIH-supported biomedical research each year, these increases have been inadequate to meet all increased needs and costs of research. The number of scientists working in biomedical research, the number of individual investigator (R01) grant applications, the proportion of each grant that goes to cover indirect costs, and the average size of each grant have all increased steadily over the years. Such factors underlie the declining success rates of applications for NIH support, from a peak of 45.3 percent in 1975 (Institute of Medicine, 1990) to only 29.3 percent in 1991 (NIH, 1992), and the prospects point to continued decline. The emphasis on obtaining funding and producing publications as measures of success for academic promotion and tenure confounds the problem, causing scientists to seek other sources of research funding. Industry is one obvious source.

Additionally, the insights associated with the genetic revolution have been more readily transferable to industry than previous technologies. As a result, many leading molecular biologists in the academic world have established complex ties with the biotechnology industry. Such relationships have become so prevalent that public agencies such as the U.S. Food and Drug Administration that need unbiased advice from knowledgeable scientists have encountered increasing problems avoiding conflicts of interest when empaneling advisory groups. Finally, both Congress and the executive branch have issued laws, regulations, and executive orders that encourage commercial development of government-funded science (e.g., the Patent and Trademark Amendments of 1980; the Stevenson-Wydler Act of 1980; the Small Business Patent Procedure Act of 1980; and the Federal Technology Transfer Act of 1986).

The types of social and ethical issues that arise from these developments include the availability and cost of new DNA-based products, delay in or reduced numbers of academic research publications due to considerations of commercial profit, "pipelining" of information or inventions to preferred companies, diversion of faculty from other university responsibilities such as teaching, delays of benefit to society, and shifts in the focus of research programs in order to optimize profitability, not scientific advance. The implications for the university of university-industry research relationships in biotechnology have been explored in depth by Blumenthal and his colleagues (1986). These issues demonstrate how social changes can have ethical implications. The issues have attracted public attention, and will do so increasingly, because of concern on the public's part that scientists maintain their honesty and integrity (so that the innovations can be reliably beneficial), their openness and cooperation (so that biomedical science can progress as rapidly as possible), and their commitment to public, not personal, gain (so that all will benefit from publicly supported research).

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