Fifty years ago this summer, the trial of 23 Nazi doctors and medical scientists for performing cruel and inhuman experiments on concentration-camp inmates led to the creation of the Nuremberg Code, a milestone in the history of medical ethics. The first line of the code, “The voluntary consent of the human subject is absolutely essential,” is generally regarded as the sine qua non for the ethical conduct of research. During the past year, institutions throughout the United States and Europe have been sponsoring events to celebrate the Nuremberg Code as a bulwark of human decency in the pursuit of scientific knowledge.

Although the ideals it embodies are now viewed as unassailable, the code was initially greeted by medical scientists as poorly conceived and unrealistic. For decades, it only sporadically influenced research ethics in policy or in practice; many doctors and scientists resisted applying the principle of informed consent to their own work. The code’s uneven influence can be attributed to the extreme circumstances of its origin, the culture of medicine at the time, and the broad phrasing its authors employed. Like so many ethical maxims (“Love thy neighbor as thyself”), the principle of voluntary informed consent seems uncomplicated. Yet 50 years after it was first articulated, we are still struggling to live up to it.

To Do More Than Hand Down Judgments

The war crimes trial of the Nazi doctors that led to the code was held in Nuremberg, West Germany, from December 1946 to August 1947. Nuremberg was chosen partly for symbolic reasons, for it was there that the Nazi Party held giant, theatrical rallies designed both to impress those faithful to the Reich and to intimidate those who opposed it.

The doctors’ trial began a few months after the conclusion of proceedings against two dozen leaders of the Third Reich, including Hermann Goering, Rudolf Hess, and Joachim von Ribbentrop. Although the American forces occupying Germany had not at first planned to conduct an inquest on human experimentation, their decision changed as information emerged about the medical atrocities committed in the concentration camps. The details of what prosecutors called “the medical case” so shocked them that they decided to pursue the matter as a war crime under the charter of the international tribunal.

Medicine had a central place in the Nazi enterprise, for the Nazis believed doctors had a special role in improving the “Volk.” Jews, Gypsies, homosexuals, the mentally retarded, and others were singled out as corrupting influences in the German national body, much like bacteria invading the individual. The view that these groups constituted a kind of public health menace implied an instrumental role for the medical profession in the business of “diagnosing” and “treating” the problem.

Although many doctors were involved in the Nazis’ racial hygiene policies-and nearly half of German doctors were Nazi party members-those who had access to concentration camp inmates for research purposes had to be well connected with the Nazi political hierarchy. Although we are not accustomed to thinking of the Nazi doctors in the mundane terms of careerism, part of their motivation was typical academic ambition. These scientists wanted to be among the first to make the medical breakthroughs that would advance the military goals of the Third Reich and make them heroes of racial medicine.

The special role given medical science in the Third Reich created an excellent opportunity for a few influential researchers to avail themselves of experimental subjects they could not have obtained under other conditions. The fact that most concentration camp inmates were eventually slated to die helped doctors rationalize their use as research subjects. The urgency of the war effort and the endorsement of the highest state authorities further encouraged these scientists to perform human-subjects research on problems of pressing concern on the battlefield.

One of these was the most efficacious way to thaw Luftwaffe fliers forced to bail out over the frigid waters of the North Sea. To test various thawing techniques Nazi researchers exposed a number of prisoners to freezing conditions and experimented with various methods of reviving them. Other experiments for military purposes included forcing subjects to drink only seawater to determine how long pilots could survive once downed in the ocean and establishing the point at which lungs exploded due to atmospheric pressures, an important issue for fighter pilots seeking to avoid anti-aircraft fire. An estimated 100,000 human beings died horrible deaths in the course of experiments at Auschwitz, Buchenwald, Dachau, Sachsenhausen, and other camps.

The brief against the defendants was delivered on December 9, 1946, by chief prosecutor Telford Taylor. In his opening statement, Taylor declared that the men were on trial for “murders, tortures, and other atrocities committed in the name of medical science.” But the prosecutors soon discovered that the case raised issues that were more problematic than they had realized-among them the lack of internationally recognized codes of medical ethics by which the behavior of the Nazi doctors could be judged. Nonetheless, nearly eight months later, after harrowing testimony about the experiments by surviving victims, the Nuremberg judges sent seven of the defendants to their deaths and sentenced eight more to lengthy prison terms. (None of those who were imprisoned served a full sentence, and many went on to distinguished careers in postwar Germany.)

The three-judge panel decided that it needed to do more than simply hand down the judgments. The members decided to codify the rules they believed should govern the use of human beings in all medical research. The Nuremberg Code begins: “The voluntary consent of the human subject is absolutely essential. This means that the person involved should … be so situated as to be able to exercise free power of choice, without the intervention of any element of force, deceit, duress, over-reaching, or other ulterior form of constraint or coercion.” The code also included provisions requiring that the scientific importance of the question be manifest, that risks to the subjects be kept to a minimum, and that prior experimentation be performed on animals.

Despite its powerful moral influence, the code carried no legal authority. No mechanisms were created to enforce it. In fact, the very circumstances that gave the code its high moral standing-the horrors that surrounded its origins-partly account for its relative lack of influence in the postwar years: ordinary researchers found it hard to believe that the code need be applied to their own work.

Extraordinary Circumstances

In the early years after Nuremberg, revulsion at the entire death-camp phenomenon was so great that it was difficult for many to see how the Nuremberg Code could apply to normal conditions. As the Yale psychiatrist and law professor Jay Katz put it, the medical community’s general attitude was, “It was a good ethics code for barbarians.” But not necessarily for everyone else. Confident of their sound motivations and humane instincts, mainstream medical practitioners felt they were inoculated against the evil that had infected the Nazi doctors. That their actions might fall into the same ethical category was difficult for most such practitioners to conceive.

The fact that the Nazi experiments occurred during wartime also made the code seem remote from the conduct of peacetime research. Although the Nuremberg judges utterly rejected national-security concerns as a rationale for the medical experiments, ordinary people may have viewed these crimes less as the actions of culpable individuals than as the result of specific national policies. While governments at war might order such extreme and brutal measures, surely few individuals would do such a thing on their own initiative.

In fact, the principle of informed consent was far from entrenched in American medical practice at the time. Most large-scale research on human subjects, spurred by World War II, was conducted by the military on institutionalized “volunteers”-conscientious objectors, prisoners, people confined to mental institutions, or, in rare cases, military personnel. Researchers preferred institutionalized subjects because it was easier to monitor them.

Although it is clear in retrospect that the Nuremberg judges purposely chose to enshrine the principle of voluntary consent in the broadest possible terms, the very sweep of their language made the code seem poorly crafted. According to historical research conducted by the President’s Advisory Committee on Human Radiation Experiments in 1994, what struck many medical researchers as especially unrealistic was the code’s seemingly categorical ban on research with any subjects who could not give voluntary informed consent. This appeared to pose an insurmountable obstacle to progress in key areas of medicine such as pediatrics and psychiatry.

The issue of research on children was an especially thorny one. Some of the most important medical research in history has been aimed at conquering childhood diseases, particularly by developing vaccines. Researchers had to experiment on children in order to ensure the effectiveness of the vaccine on its target population and determine the proper dosage. Some of these experiments were of enormous benefit to their subjects as well as to future generations of children. Nonetheless, it was widely recognized that children are not capable of granting consent. The question confronting researchers, then, was whether the authors of the code intended to abandon this whole field of research, even at the cost of saving children’s lives.

The by-now-familiar solution was to establish parental permission as the moral equivalent of the child’s consent, on the grounds that parents will act in the best interest of the child. Although obtaining parental consent became standard practice by the late 1950s, it was not required by federal regulations until the late 1970s. This resolution extended to the most vulnerable members of society the principal lesson of Nuremberg.

However, not all of society’s vulnerable members were equally well protected. Because there were fewer advocates for the mentally ill than for children, the federal government has never enacted regulations specifically targeting the use of psychiatric patients in research. Research on prisoners-another group whose ability to grant consent is compromised-continued through the mid-1970s, when political pressures from a variety of sources forced the federal government to declare a halt on the grounds that consent cannot be truly voluntary in an inherently coercive environment.

The Doctor Knows Best

Physicians in the United States gradually became willing to concede that the use of unconsenting subjects in experiments that could not benefit them was a dangerous encroachment of science on personal privacy. But therapeutic research-studies involving sick patients who might in some way benefit from experimental treatment-was a different story. Doctors jealously guarded the “therapeutic privilege,” the right to withhold information from patients.

Although the field of medicine was changing rapidly, the culture of medical practice still operated largely on an old- fashioned, paternalistic model. According to this view, the trusting, nearly sacred relationship between doctor and patient was based on the premise that the doctor knows best; a good patient was defined as a compliant one. Even if the physician’s care involved the use of experimental drugs or devices as part of a scientific study, doctors were reluctant to involve patients in making decisions about their own care.

Nothing symbolized doctors’ fears of intrusion into their relationships with patients more than consent forms. In the early 1950s consent forms were used in certain exceptional cases (such as invasive procedures that simply could not be performed without a patient’s knowledge and cooperation) but not in the vast bulk of therapeutic research. For the most part, the privacy of the doctor-patient relationship was accepted as serving the public interest.

The philosophy of medical paternalism was codified in the 1964 Helsinki Declaration. Partly in response to the consent problems posed by the Nuremberg Code, the World Medical Association had begun deliberations to formulate its own research code in 1953. The resulting document drew a sharp line between therapeutic and nontherapeutic research; doctors were not required to obtain consent for experimental procedures performed on their patients if this requirement was not “consistent with patient psychology.” This might apply, for instance, to terminally ill patients who could become depressed and unwilling to undergo further treatment if informed of their prognoses.

Few doctors involved in research in the 1950s paused to reflect on the contradictions between their own roles as caregivers and as researchers-the so-called double-agent problem. For example, from the 1940s through the early 1960s, scientists performed a series of secret, government-sponsored radiation experiments on patients who were hospitalized, institutionalized, or seeking treatment for other conditions (such as pregnancy), often without obtaining the patients’ consent. When records of these experiments recently became public, they provoked widespread outrage. At the time, however, there was no mechanism requiring scientists to obtain consent from their subjects. And even though the researchers must have been aware of the existence of the Nuremberg Code, it is doubtful that they felt its provisions applied to research conducted in the context of the doctor-patient relationship.

An Emerging Consensus on Consent

Together these factors worked against implementing the consent requirement of the Nuremberg Code in any formal or consistent fashion in the first decade after it was articulated. But in the early 1960s a wave of medical scandals brought the issue of informed consent to the fore. In 1963, a university team conducted a well-publicized but medically doomed effort to transplant a chimpanzee kidney into a human patient-an experiment conducted partly with federal funds, but without prior animal studies or valid scientific justification. The episode heightened concern about the lack of scientific or government oversight of research using human subjects.

A few years later, Harvard anesthesiology professor Henry Beecher, in an article in the New England Journal of Medicine, claimed to have found 22 obvious abuses of human subjects in the recent medical literature. In one of these cases, researchers injected live cancer cells into debilitated patients at the Brooklyn Jewish Chronic Disease Hospital without the subjects’ knowledge in order to determine whether their immune systems could mount a defense against the cancer. (The subjects were not harmed by the experiment.)

In 1966, the surgeon general announced a policy to govern human-subjects research supported by Public Health Service grants. It required institutions receiving PHS support to create an institutional review board to oversee research involving human subjects and demanded that researchers obtain consent from their subjects.

But if a single event broke the back of medical paternalism in research it was surely the Tuskegee syphilis study. From the early 1930s to the early 1970s, U.S. Public Health Service doctors had studied more than 400 black men with syphilis in Macon County, Ala. The men were not told they had the disease, nor were they offered treatment-even after the discovery of penicillin made treatment much more effective. When a journalist broke the story, a firestorm of outrage swept the country. The requirement for the “voluntary consent of the human subject” had been systematically abused right here in America, in a study that had begun just around the time the Nazis took power in Germany.

The federal government appointed a commission to investigate the scandal in 1972. Recommendations based on its findings, released in 1978, were incorporated into Department of Health and Human Services regulations in 1981 and extended to all federal agencies conducting or sponsoring human-subjects research in 1991. As a result of the Tuskegee scandal, the requirement for voluntary consent in research became deeply etched in the law and in the minds of many who had not seen the need for vigilance before.

The Code Today

lthough it took decades to gain wide acceptance, the Nuremberg Code exerts a profound influence on the conduct of medical research today. An excellent example is the recent ruling by the Food and Drug Administration (FDA) governing research in the emergency room.

Because standard treatments for some conditions, such as head injuries, are ineffective, doctors want to try experimental drugs and devices that they consider promising, based on laboratory work and animal testing. But many emergency room patients suffering from these conditions are unconscious and relatives may not be present. The inability to obtain consent has slowed the pace of vitally needed research.

The FDA ruling permits researchers to enroll patients with life-threatening conditions in certain studies even if they are unable to grant voluntary informed consent, but only if they have informed the community that such studies are going on and that anyone who is admitted to the emergency department with a serious condition could be assigned as a subject. While media accounts have portrayed the FDA decision as a step back from the principle of informed consent, the fact that the agency had to make an explicit exception shows the tenacity with which we now embrace it. The ruling represents one step in the continuing effort to walk the fine line between medical progress and human rights.

The Nuremberg Code also contributed to a sea change in public attitudes toward research, which in turn has spurred debate over access to experimental treatments. It took decades to develop a consensus within the medical community that even ordinary science conducted by well-meaning researchers can lead to unintended harm. Today a system of carefully designed regulations protects desperate people from medical experiments that might only make them worse. In fact, the protections built into the system are so successful that people have become confident of low risks and high benefits if they are granted access to experimental drugs.

In the 1980s, AIDS activists mounted a series of successful campaigns to broaden access to experimental drugs such as AZT. Similarly, women of reproductive age, who were systematically excluded from many drug trials following the thalidomide tragedy of the early 1960s, have sought to participate equally in research in order to capture the potential benefits of experimental treatments and ensure that drugs or devices are developed to meet their needs. For instance, women excrete medications at different rates than men, and since women are more likely than men to use prescription drugs, advocates have argued that they should be better represented in research studies.

Today, concern about informed consent in medical research is greater than ever. In response to the uproar over the Cold War radiation experiments, President Clinton recently announced that henceforth all secret human research conducted in the name of national security would be subject to the rules of informed consent, and that scientists would reveal the names of the sponsoring agencies to participants. What’s more, Clinton’s advisory commission on bioethics, appointed last year, will undertake a review of current practices and requirements regarding the use of human subjects. In particular, the commission should address ways to ensure that voluntary consent is meaningful.

For instance, there is evidence that seriously ill patients often overestimate the likelihood that they will benefit from experimental treatments. Early trials of a new drug may be designed to determine its effects on the body, such as the rate at which it is excreted-not whether or not it is likely to cure the patient. In fact, most experimental treatments don’t work. In order for consent to be truly voluntary, the commission should require that sick patients receive counseling to ensure they understand the implications of research for themselves.

Another issue confronting the commission is whether states should enable people to declare in advance of a serious illness and loss of capacity their willingness to be a research subject in a study that might help them. At least some people who may be candidates for emergency-room research might be willing to make such an advance declaration. This measure would enable researchers to continue to investigate experimental emergency-room treatments without relying so heavily on unconsented research.

The principle of informed consent continues to pose new dilemmas for medical science. It is not always easy to find the balance between human rights and scientific progress. Yet the simplicity and intuitive force of the ideas articulated in the Nuremberg Code ensure their lasting moral relevance.