The Nuremberg Code of ethical principles for experiments involving human beings has as its first requirement that “the voluntary consent of the human subject is absolutely essential.” Since the time of the trials that supplied its motivation the principles have been amplified and detail and distinctions have been added. For example, the Declaration of Helsinki, adopted by the World Medical Association in 1964, again laid down general principles related to voluntariness, balance of risk and benefit, and scientific soundness. However, it also noted that the ethical issues with regard to two distinctly different types of human experiment vary. These two types are clinical research (i.e., “medical research combined with profession care”) and nonclinical biomedical research (i.e., “nontherapeutic biomedical research involving human subjects”). In actuality, we may distinguish three types of human biomedical experimentation. Two of these are therapeutic and nontherapeutic experimentation. The first is directed primarily to the benefit of the experimental subjects who are being treated with some new experimental therapy for their ailment. In the second an experiment is designed to increase medical knowledge and uses volunteers who are healthy or whose illness is not related to the experimental study. One key difference between the ethical requirements specified by the Declaration of Helsinki for therapeutic and nontherapeutic experimentation was that the second approach required participation only by volunteers whom we assume are able to and do give their informed consent. However, in the first approach if consent were not obtained, the physician must specify the reasons and present these before an independent committee.

“[A] murder prosecution is a poor way to design an ethical and moral code for doctors,” observed the California Court of Appeal in 1983. Yet, physicians who have chosen to help terminally ill patients to commit suicide have trespassed on illegal ground. When skilled medical care fails to relieve the pain of terminally ill patients, some people believe that physicians may assist in these suicides. Others reject any kind of physician involvement. The debate on assisted suiczide and active euthanasia has focused on whether these acts can ever be acceptable. We propose to shift the debate to a less divisive issue: whether a caring physician who provides a suffering and ill patient with a prescription for a lethal dose of medication should be prosecuted as a felon. Even assisted suicide's opponents may object to such criminal prosecution. We propose to modify existing criminal laws to give physicians who assist their terminally ill patients in suicide, under carefully defined circumstances, a legal defense against criminal charges.

The voluntary and informed consent of subjects has been the central focus of concern in research reviews, overshadowing the importance of all other considerations. The Nuremberg Code, with its rights-based protection of the subject's autonomy above all else, made it difficult to justify research with no intended benefit when subjects are incompetent to make a valid informed choice to participate. Subsequent codes providing for research with incompetent subjects followed the lead of Nuremberg, substituting the informed authorization of a proxy for the informed consent of the subject.

Mr. Bernard was a homeless man, aged 58. His medical history revealed alcohol abuse, seizure disorder, and two suicide attempts. Brought to the emergency room at a local hospital after being found “semi-comatose,” his respiratory distress led to his being intubated and placed on a ventilator. The healthcare team suspected the patient ingested antifreeze. Transferred from that hospital to the intensive care unit (ICU) of the university hospital, his diagnosis was “high osmolar gap with high-anion gap metabolic acidosis, most likely secondary to ethylene glycol ingestion and renal insufficiency.”

Physician-assisted suicide is a novel idea having affinities with both suicide and euthanasia. It has affinities with suicide because it involves a self-inflicted death, and it has affinities with euthanasia because the physician is instrumental in the death. It is, however, not exactly either, making it the subject of an exciting debate.

Research is ongoing concerning the medical risks and benefits of routine neonatal male circumcision. Interpretation of the data, however, is controversial. Circumcision presents a number of challenges in obtaining informed consent because of a variety of interesting issues. It is a nonemergent, elective procedure that allows for evaluation and discussion over time. In this respect, observation of the informed consent process for circumcision is relevant to other medical decisions, such as advance directives, discussed between primary care providers and patients. Obtaining informed consent for circumcision has its constraints. The process generally occurs over a brief hospital stay. There have been recent changes in the official position regarding the procedure by professional medical societies, and it raises considerable psychologic issues for the provider and may Impact the way in which Information is provided.

Among the many striking features of modern medicine is one that has rarely received its due, save by those specialists in the arcane and remote: medical historians. Medicine is a profoundly historical enterprise, deeply marked by and in continuous, if only implicit, dialogue with its own history. Historical reflection on medicine is therefore an especially compelling undertaking. A case in point: scratch almost any physician today and you find an abiding commitment to “Hippocmtic morality.”

It is universally accepted that informed consent to participate in medical research should be given by subjects. People have the fundamental human right to freely choose, without coercion or withholding of information necessary to make a reasonable choice, whether they will undergo any risks associated with a research project. United States researchers have known for some time that they have the duty to inform potential subjects of the nature of proposed research and the risks and possible benefits, and to seek consent. Investigators also have the duty to design the research so that it will be scientifically valid while minimizing foreseeable and avoidable harms.

No discussion of the informed consent process would be adequate without attention to dilemmas and challenges arising in research in foreign countries, particularly in the less developed countries. In an era of the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), for example, much attention to research issues concerning devastating health conditions in developed and less developed countries has occurred with renewed vigor.

There has been no informed or honest debate in North America over the issue of liberalized euthanasia. Despite thousands of newspaper stories, scores of learned academic articles, a handful of closely analyzed legal decisions, and hours of broadcast news and talk show imagery, a full discussion is yet to begin.

Assume this hypothetical situation: an American pharmaceutical company, Maxwell Fisch Pharmaceuticals, Inc. (Maxwell), wishes to perform clinical trials involving a new antipsychotic medication, Klezac. Klezac is in its third phase of the clinical stage of the drug research process. Once the testing is complete, Maxwell plans to submit a New Drug Application, the official request to begin marketing Klezac, to the Food and Drug Administration (FDA). The new drug is expected to receive FDA approval in 2 or more years. The company decides to shift its research and development activities to Z, a small, developing country. In doing so, Maxwell is following the course taken by numerous other drug companies who wish to take advantage of faster governmental approval in foreign sites and ensuing cheaper research costs.

Several inquires about healthcare over the past several decades have shown that the evolution of healthcare practices exhibit their own microcosm of local and political influences. Likewise, other studies have shown clearly the ways in which both external and internal institutional factors establish the sectors within which healthcare is delivered. Although restrictions have always been present in some form, it seems obvious that whatever the precise form of healthcare delivery that results from current changes in its organization, there are going to be broader restrictions not only on the choices that providers will be able to make about individual patients' care and needs, but also regarding the character of their clinical judgments. Indeed, there are already reports of instances where physicians' contracts with managed care organizations forbid them to disclose the existence of services not covered by a plan.

In advanced technological societies there is growing concern about the prospect of protracted deaths marked by incapacitation, intolerable pain and indignity, and invasion by machines and tubing. Life prolongation for critically ill cancer patients in the United States, for example, literally costs a fortune for very little benefit, typically from $82,845 to $189,339 for an additional year of life. Those who return home after major interventions live on average only 3 more months; the others live out their days in a hospital intensive care unit.

Today's clinical AIDS research is in trouble. Principal investigators are confronted with young and frequently highly knowledgeable patients. Many of these people with AIDS (PWAs) are often unwilling to adhere to the trial protocols. These PWAs believe they are ethically justified in breaching trial protocols because they do not consider themselves true volunteers in such trials. PWAs argue that they do not really volunteer because existing legislation prevents them from buying and using experimental drugs or from testing alternative treatment strategies. Their only access to such agents is participation in clinical trials.

What proportion of available healthcare funds should be allocated to hip replacement operations and what proportion to psychiatric care? What proportion should go to cardiac patients and what to newborns in intensive care? What proportion should go to preventative medicine and what to treating existing conditions? In general, how should limited healthcare resources (people, facilities, equipment, drugs…) be distributed If not all demands can be met?

The institutional review board (IRB) Is charged with assessing the risks and benefits of research projects Involving human subjects. Ethical considerations and federal regulations require that an IRB, in part, must find that the potential risks of participation are proportional to the potential benefits (If any) and to the Importance of the knowledge that may be learned before the IRB can approve the voluntary assumption of risk by a research participant. Adequate assessment of the risks and benefits requires careful scrutiny of the study design In relation to the study objectives.

D.T. a 35-year-old woman, was found to have breast cancer. At the time of mastectomy axillary lymph nodes were positive and the cancer was classified as adenocarcinoma, grade 4. The patient underwent conventional chemotherapy. When it became apparent the disease was metastatic, the patient's oncologist contacted a well-known cancer center regarding the possibility of treating the patient with high dose chemotherapy and autologous bone marrow transplantation (HDC/ABMT). The patient's health insurance provider informed the patient, however, that the treatment—estimated to cost in the range of $150,000–200,000—was “considered experimental or research in nature” and therefore was not included in coverage. D.T. did not pursue this further. Approximately 2 years later, cancer was detected in the patient's spine. This time she applied to another well-known cancer center for HDC/ABMT. The cancer center agreed to accept her on the condition of proof of ability to pay for the treatment. Again her insurer refused coverage on the same grounds as before. D.T. found another source for the money, underwent treatment, then sued the insurance carrier. She sought a declaratory judgment that the treatment was covered under the insurance policy. The court ruled in favor of D.T. finding the contract phrase “considered experimental” ambiguous.

I graduated from medical school in 1957. I first went into hospital practice for 3½; years, and then went to Africa for 5 years before returning to Holland to resume practicing as a Family Physician. I have also participated in the postgraduate training and education for family doctors in Amsterdam, Currently, there are approximately 2,300 patients in my practice, about average for a Dutch physi- cian. Ten percent of those patients are over the age of 65.