Efforts to improve the means to diagnose and treat human genetic diseases have a long history in biomedical research and medicine. Now, preimplantation genetic diagnosis (PGD) provides a new way to prevent the transmission of certain types of human genetic diseases to the next generation. It is an alternative to elective termination of pregnancies.

PGD is used to test for genetic diseases that are due to defective single genes or abnormal chromosomes within days of fertilization and prior to the establishment of pregnancy. The procedure essentially begins with the biopsy of one or more cells of a cleavage stage or blastocyst stage preimplantation human embryo that has been produced by in vitro fertilization (IVF). In certain cases, PGD can be done on polar bodies—discarded by-products of egg formation containing excess chromosomes—of unfertilized eggs. Then, the cell(s), or a polar body, is placed into a tube for single gene analysis (DNA analysis by polymerase chain reaction (PCR)), or for chromosome analysis by spreading the nucleus of the cell on a microscope slide (fluorescence in situ hybridization (FISH)).

The capacity to treat pain has never been greater; but, as you will read in the articles that follow, the problem of undertreated and neglected pain in the United States persists. Deep-seated perceptions and practices undergird this strong and well-documented pattern of neglect. Among the reasons frequently noted for the inadequacy of treatment for pain, however, is that the legal system actually penalizes effective interventions to relieve pain while it leaves neglect of pain unthreatened. It is the mission of the American Society of Law, Medicine & Ethics (ASLME) to explore areas, such as this one, where developments in medicine directly encounter the law and, in turn, create ethical issues for clinicians, regulators, patients, and lawyers.

This special issue of the Journal of Law, Medicine & Ethics is part of a multi-year project in which ASLME, with the wonderful support of the Mayday Fund, has worked to address legal and regulatory barriers to effective pain relief.

Responding to mounting public concern about the shift to managed care, legislation to grant patient protections has dominated the health policy agenda over the past two years. Although some policies, such as laws on maternity length of stay, can be easily dismissed as “body part by body part” micromanagement of medical practice, other initiatives offer substantive, new rights to patients across the spectrum of care. At both the state and the federal levels, the right of enrollees to appeal a denial of treatment or to file grievances about other plan decisions has emerged as a centerpiece of patient protection legislation. Grievance and appeal rights have been embraced as a way to empower patients, to enhance access to treatment, and to improve the quality of care by providing an external mechanism to review treatment denials.

The problem of inadequate pain management for both terminally ill patients and patients with chronic pain has recently been documented by a number of authors and studies. A 1997 report by the Institute of Medicine (IOM), for example, states that “a significant proportion of dying patients and patients with advanced disease experience serious pain, despite the availability of effective pharmacological and other options for relieving most pain.” There are particularly impressive data that pain associated with cancer is not adequately treated.

The problem has been attributed to (1) inadequate education of physicians on approaches to pain management and an often misguided belief that prolonged therapy with certain pain medication will lead to addiction; (2) legal obstacles, such as physicians’ fear of criminal prosecution and other disciplinary actions by state licensing boards for overprescribing narcotics; and (3) inadequate insurance coverage as a result of narrow eligibility criteria for hospice care for Medicare beneficiaries, and inadequate reimbursement more generally for pain management and palliative care.

Managed care has brought wide-ranging changes to the health care system. Some of these changes have been well publicized. Among them are the financial pressures that have resulted in numerous mergers of health care institutions, the restriction on the ability of patients to select their physician of choice, and the ever diminishing number of days that patients are permitted to stay in the hospital. Individual physicians, too, have been affected. For example, they are under pressure to see more patients per unit time and to use fewer resources. Utilization review and payment methods may make them reluctant to undertake the full set of diagnostic tests and therapeutic interventions when they might otherwise have done so.

Preimplantation genetic diagnosis (PGD) is a new method of prenatal diagnosis that is developing from a union of in vitro fertilization (IVF) technology and molecular biology. Briefly stated, PGD involves the creation of several embryos in vitro from the eggs and sperm of an interested couple. The embryos are permitted to develop to a 6-to-10-cell stage, at which point one of the embryonic cells is removed from each embryo and the cellular DNA is analyzed for chromosomal abnormalities or genetic mutations. An embryo or several embryos found to be free of genetic abnormalities are subsequently transferred to the woman's uterus for gestation. Embryos found to carry a genetic abnormality are discarded or frozen. Extra normal embryos may be frozen for future transfer or donation to another couple.

We are living through one of the greatest scientific revolutions in history: the “information revolution” in genetics. The revolution is leading to a deep understanding of biological processes and is uncovering the molecular basis of many human diseases and susceptibilities. It is also confronting society with a vast array of choices, and presenting each individual with the question of what knowledge to seek and how to act on that knowledge, My purpose is to discuss the scientific foundations of this revolution and to foreshadow its consequences.

The current scientific revolution has perhaps one appropriate historical precedent: the chemical revolution that followed Dmitri Mendeleev's key insight in 1869 that the elements could be organized in a simple periodic table.

The surge in genetic research and technology, fuelled in large part by the Human Genome Project, has resulted in the continuing expansion of the range of genetic tests and other genetic information available to physicians, insurance companies, employers, and the general public.’ Genetic tests can provide presymptomatic medical information about an individual, including information about an individual's increased risk of future disease, disability, or early death. These tests can reveal information about an individual's carrier status, that is, the likelihood of parents passing on to their children a genetic condition, and about the health of the individual's family members. Although genetic information provides the promise of early detection and treatment of certain illnesses and disorders, it also poses risks. As a result of the increase in genetic testing and information, legal issues regarding employment discrimination on the basis of genetic information are emerging.

The general perception of how innovative assisted reproductive technologies (ART) are introduced is through a carefully controlled series of experiments in an animal model, such as the mouse. Only after the technique has been proven can one consider confirmatory studies on mammals closely related to humans, such as rhesus monkeys or other nonhuman primates. With this background of a peer-reviewed body of well-established published data, there is sufficient foundation and rationale to propose a clinical investigation to a responsible human subjects institutional review board (IRB). IRBs weigh the benefits and risks of the new methods to human subjects, and then consider the appropriate informed consent procedures for the particular case. Only after a large number of clinical studies are performed at multiple sites and are peer reviewed can the efficacy and safety of the innovative approach be clearly evaluated. At that time, the potential therapy can be responsibly offered to suitable beneficiaries.

The United States, unlike all other industrialized nations, does not have a comprehensive public system for financing health care. Nevertheless, the magnitude of America's public health care financing effort is remarkable. Of the one trillion dollars the United States spent on health care in 1996, almost half, $483.1 billion, was spent by public programs. In 1995, Medicare—our social insurance program for persons over sixty-five and the long-term disabled—overed 37.5 million Americans; Medicaid—our program for indigent elderly and disabled persons and indigent children and their families—covered 36.3 million. In 1996, Medicare and Medicaid spent $203.1 and $147.7 billion, respectively. The payment policies of these massive public health care programs have a profound effect on the provision of health care.

Many of the recipients of Medicare and Medicaid suffer pain. In 1994, 376,200 Americans over age sixty-five died of cancer. Virtually all of these would have been Medicare recipients, and as many as 70 percent of them died in unrelieved pain. Nearly four million Americans over sixty-five endured the pain of inpatient surgery in 1995, again nearly all of whom were Medicare recipients.

Two significant, apparently unrelated, trends have emerged in American society and medicine. First, American medicine is reexamining its approach to dying. The Institute of Medicine, the American Medical Association and private funding organizations have recognized that too many dying people suffer from pain and other distress that clinicians can prevent or relieve. Second, this past decade has marked a sharp increase in the number of physicians prosecuted for criminal negligence based on arguably negligent patient care. The case often cited as a watershed is People u. Einaugfer, which involved a New York nursing home patient whose physician was convicted in 1993 of two criminal misdemeanors after he ordered an elderly dialysis patient to be tube fed through a peritoneal dialysis Catheter.

How is the growing awareness of dying patients’ pain and the increasing willingness of prosecutors to charge physicians with crimes connected? Pain at the end of life is frequently treated with narcotics, prescription drugs that are closely regulated by state and federal law. That complex web of laws—and a growing fear of legal sanctions—has deterred physicians from prescribing controlled substances. As those legal sanctions move from disciplinary actions to criminal charges, physicians’ fears may expand.

In March 1996, the General Accounting Office (GAO) issued the report Scientific Research: Continued Vigilance Critical to Protecting Human Subjects. It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always clear to clinicians. Controversy exists regarding whether certain medical procedures should be categorized as research.”

This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health (NIH) Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy.

Genetic privacy and confidentiality have both intrinsic and consequential value. Although general agreement exists about the need to protect privacy and confidentiality in the abstract, most of the concern has focused on preventing the harmful uses of this sensitive information. I hope to demonstrate in this article that the reason why genetic privacy and confidentiality are so difficult to protect is that any effort to protect them inevitably implicates broader and extremely contentious issues, such as the right of access to health care. Moreover, the tentative legislative and policy steps undertaken and proposed thus far have been, for the most part, misguided, simplistic, and ineffective.

Hospitals long ago shed their role as alms houses for the poor. What vestiges remain of the early American hospital are the tax-exempt, nonprofit hospital form and a general perception that hospitals, as charitable institutions, owe a duty to their communities. The appropriateness of the nonprofit hospital tax exemption has long been debated, and many theories have been advanced to justify the tax exemption of nonprofit hospitals. In a growing number of jurisdictions, however, state and local authorities have gone beyond the theoretical debate and are challenging the tax exemption of their nonprofit hospitals. For various reasons, efforts are afoot to capture greater community benefit from nonprofit hospitals.

At the heart of such challenges is the debate over the nature and extent of the duty charitable institutions owe to their communities. A demand is growing for nonprofit hospitals to earn their tax exemptions by benefiting their communities in concrete ways. Some have been stripped of their tax-exempt status by local authorities or pressured to make payments in lieu of taxes. A number of states have recently implemented initiatives in an attempt to make hospitals more accountable for their community benefits. Many hospitals are responding to this heightened scrutiny in a proactive way, by voluntarily documenting community benefits. A number of nonprofit hospitals and hospital associations are cooperating with—or even sponsoring—state legislation in this area.