"Ethics and clinical research" revisited: a tribute of Henry K. Beecher.
Subject: Human experimentation in medicine (Ethical aspects)
Informed consent (Medical law) (Ethical aspects)
Author: Katz, Jay
Pub Date: 09/01/1993
Publication: Name: The Hastings Center Report Publisher: Hastings Center Audience: Academic; Professional Format: Magazine/Journal Subject: Biological sciences; Health Copyright: COPYRIGHT 1993 Hastings Center ISSN: 0093-0334
Issue: Date: Sept-Oct, 1993 Source Volume: v23 Source Issue: n5
Persons: Named Person: Beecher, Henry K.
Accession Number: 14469178
Full Text: The doctrine of informed consent, borrowed from the law of torts, cannot be readily transplanted into therapeutic settings. The broader, as yet unrealized, idea of informed consent, which suggests that parties must make decisions jointly, should guide interactions between physicians and patients or investigators and subjects.

I want to pay tribute to Henry Knowles Beecher by reflecting upon the ethics of human experimentation, past and present. He, and I somewhat later, became absorbed in this topic years prior to the flowering of bioethics. By June 1966, when he published his courageous article "Ethics and Clinical Research,"[1] we had met and talked often about our hopes and fears. We knew that we were exploring uncharted territory, discovering a world whose ethical dilemmas were there to be seen but had largely been ignored. We hoped that our inquiries would persuade our colleagues to examine in depth physician-investigators' responsibilities to medicine, medical science, and patient-subjects in the enterprise of extending the frontiers of medical knowledge. At the same time, we were concerned about the reception our work would receive from the medical community.

I had become interested in human experimentation in late 1964 or early 1965. Many reasons of the heart and mind had sparked my interest. As I reflect upon these origins and my work during the subsequent thirty years, I realize that it has always been my heart that led the way. Only later did my mind begin to impose some order on intense feelings that I can trace back to a number of personal experiences.

First, while on the faculty of the Yale Medical School I had conducted research with "volunteer" subjects. I was then largely oblivious of my responsibilities to disclose to them fully the risks that their participation might entail. My colleagues and I were aware of potential risks. We had taken precautions to minimize them and, should they materialize, to repair any damage. It did not occur to us, however, to share our concerns with our subjects so that they could decide whether or not to take these risks. The unique responsibilities physicians confront in the conduct of research had not been discussed in my medical education, even though we were encouraged to do research.

Second, when I joined the faculty of Yale Law School it was my custom to attend one course or seminar each year in order to learn more about law. One afternoon in the early 1960s I witnessed an intense debate between students and their teacher about how best to protect an accused from the powerful array of forces that the State can so inexorably align against him or her. I was struck by the students' zeal to safeguard the rights of the accused. Their sense of justice and fairness made quite an impression on me. Suddenly I realized that I had stopped listening. Instead, my thoughts had taken me back to my research, and I remembered how little attention I had given to the rights of my research subjects. In subsequent months I often recalled that afternoon and the memories it had evoked. The idea of studying what transpires in human experimentation increasingly captured my imagination.

A third chance encounter reinforced my intention to study the human research process. While perusing a casebook on criminal law, I ran across the trial transcripts of the Nuremberg proceedings against the Nazi physicians. The history of the medical experiments conducted at Auschwitz, Dachau, and other concentration camps had also not been part of my medical school education. The transcripts recounted in sickening detail these medical experiments, carried out "with unnecessary suffering and injury, and... very little if any [protection of subjects from] injury, disability, or death."[2] I had lost many of my cousins, aunts, and uncles in the Holocaust. How many of them, I wondered, had been condemned to participation in these experiments?

I began to immerse myself in the then scant literature on human experimentation conducted in the Western World. I soon realized that the moral, medical and legal dilemmas posed by such research could not be adequately resolved, as generations of doctors had assumed, by a pledge of allegiance to such undefined principles as primum non nocere or to vague aspirational codes. Better safeguards had to be provided, and whatever they might turn out to be, required sustained reflection.

My First Conversations with Beecher

Thus in January 1966 and for the first year with my late colleague Richard Donnelly, I began to teach at Yale Law School a semester-long seminar on the control of human experimentation. The seminar, probably the first of its kind, was announced in the 1956-66 Yale Law School Bulletin rather tersely:

EXPERIMENTATION ON PEOPLE 2 Units. An examination of the variety of "therapeutic" and "experimental" medical procedures which have been carried out on patients and normal volunteers. Central to this exploration will be a detailed study of consent and the role of the state in the supervision of medical experimentation.

While preparing teaching materials for the seminar, I ran across Henry Beecher's monograph Experimentation in Man, published in 1958. He had been my teacher at Harvard Medical School and his lectures on anesthesia had made quite an impression on me. I decided to call him. He told me that he had become even more absorbed in the study of the ethics of clinical research. When I invited him to one of my classes, he accepted eagerly, and during the spring semester of 1966, he returned often to New Haven. We talked and talked. He also made me drink more martinis than I had ever been accustomed to. Remember, these were the months prior to the publication of his 1966 article, and he was quite worried. My students cheered him up. He had made a profound impression on them, not only by what he taught them, but by the moral passion that punctuated his every word.

Those were the days prior to the birth of bioethics. Neither Beecher nor I was interested in creating a new discipline. We came to the study of human experimentation out of a newly acquired conviction that research subjects deserved to be treated with greater respect and that our colleagues had paid too little attention to an increasingly widespread dimension of modern medical practice. As Beecher wrote in the introduction to his 1958 monograph: "The breaches of ethical conduct which have come to [my] personal attention are [the result of] ignorance or thoughtlessness. They were not willful or unscrupulous in origin. It is hoped that the material included here will help those who would do so to protect themselves from the errors of inexperience."[3]

He wanted to teach, not to indict. I too intended to sensitize physicians to the many tensions inherent in the conduct of human research and urge them to study these problems in greater depth. In my first public lecture on human experimentation at Yale Medical School, one and one-half years prior to the publication of Beecher's article, I pleaded that medical schools must become centers for the study of the problems posed by human experimentation. The lecture was not well received. I was criticized for speaking about matters that should not be aired in public.

I realized then that regulation would be inevitable and my exposure to the world of law had begun to teach me a great deal about regulation. Thus, my students and I began to explore such questions as: Who should define the rights and duties of the parties involved in human experimentation, and who should supervise their implementation? The common law doctrine of informed consent,[4] barely five years old, loomed large in our deliberations. I thought then that it showed considerable promise in providing greater protection to subjects of research. Even though as early as 1947 the Allied Military Tribunal had made "voluntary consent" the cornerstone of its Nuremberg Code, that prescription had made little impact on the conduct of research. Perhaps informed consent would fare better.

After revising draft after draft of my class materials over seven years, I finally, in 1972, published a casebook called Experimentation with Human Beings. In its later stages, Eleanor Swift Glass and Alexander Morgan Capron joined me as research assistants. Alex made major and significant contributions to its final version, and once again I want to acknowledge my great debt to him. Extensive sections of the book explored the functions that informed consent could serve for the human experimentation process. That analysis was embedded in a more general examination of the extent and limits of a subject's ability and authority to make decisions on his or her behalf. Equally prominent were materials that sought to explore problems of regulation. Here the overall question was this: "What persons and institutions should have the authority to formulate, administer, and review the human experimentation process?"[5]

As it had been Beecher's hope for his writings, so it was my hope that the book would encourage and facilitate an intensive study of human experimentation and provide better protection for the subjects of research. I believe that my book made a contribution, albeit a limited one, toward that objective. From the perspective of history it will always remain unclear whether the gains I achieved were the result of the book or the public reaction to the Tuskegee syphilis study, both of which date to 1972. I served on the ad hoc advisory panel convened by the Department of Health, Education, and Welfare to investigate the Tuskegee affair, and I wrote the section on our third charge, to make recommendations about necessary changes in "existing policies to protect the rights of patients participating in health research." Our eventual recommendations were largely based on what I had learned over many years.

The Penchant for Theorizing and Abstracting

Before addressing my misgivings about the contemporary protections afforded to subjects of research, I want to go back once again to Beecher's and my early work, and to the birth of bioethics. Our initial explorations were not influenced by theoretical considerations but by concerns that human beings were not being treated with the respect they deserved. In my case this work was also influenced by an ever increasing sense that the conduct of research was often at odds with fundamental democratic values. In short, we were primarily interested in customary medical practices that eventually might call for theoretical formulations.

Leon Kass in his wonderful address at the Twentieth Anniversary Meeting of The Hastings Center illuminated what I here wish to convey. He deplored the penchant of bioethicists, soon after bioethics' birth, for theorizing and abstraction, their emphasis on extreme examples rather than on "the morality of ordinary practice."[6] He pleaded that "we must think less about doctrine and principles [and more] about how to encourage and enhance the formulation of certain sentiments and attitudes. We must return to what animated the [bioethics] enterprise: the fears and hopes, the repugnancies, the moral concerns, and, above all," he asked us to remember "that beneath the distinctive issues of bioethics lie the deepest matters of our humanity" (p. 12). These were Beecher's and my objectives - Beecher's more than mine perhaps. I have engaged in some "theorizing," though I think not with the same penchant for abstraction that Leon Kass deplored.

Our work was grounded in cases. We came to the study of human experimentation out of deeply felt "moral concerns" about medical practices. We felt, to quote Kass again, that there was a "need to think about how to encourage and enhance the formation of certain sentiments and attitudes; [a need to think about] respect, reverence, and gravity [and] what fosters them and undermines them" (p. 11). We believed our inquiries addressed "the deepest matters of our [medical] humanity": the interactions between physicians and patients in medical practice that since World War II had become increasingly infiltrated by the claims of science and its use of patients for the sake of future patients.

From the perspective of hindsight, Beecher and I were not entirely correct in what we emphasized and neglected to stress. In his 1966 article, "Ethics and Clinical Research," Beecher found that twelve of 100 consecutive human studies published in 1964 in an excellent journal" had been "unethical" (p. 1355). It led him to make these "troubling charges": "that many ... patients ... never had the risks satisfactorily explained to them [and that many] have not known that they were the subjects of an experiment although grave consequences have been suffered as a direct result of [these] experiments" (p. 1354). His startling allegations, of course, raise doubts about his accompanying assertion "that American medicine is sound, and most progress in it soundly attained." I pointed this out to him, and he was of two minds about what he had said. Yet he had needed to put it that way in order to support his ultimate conclusion as to remedies: "The ethical approach to experimentation in man has several components ... the first being informed consent [and the second] the more reliable safeguard provided by the presence of an intelligent, informed, conscientious, compassionate, responsible investigator" (p. 1360). Beecher had greater faith in the second than the first prescription. However, there are intertwined problems with his second prescription. It requires first a thoroughgoing reappraisal of the values that should govern the human experimentation process. Only then can physician-investigators begin to learn how to conduct themselves conscientiously and responsibly to fulfill their new moral responsibilities toward patient-subjects and the claims of science.

Turning to My Work

I want to describe briefly the impact of theory on my primary objective of sensitizing physician-investigators to their moral responsibilities toward subjects of research. I believe that my theoretical formulations always stayed close to concerns about the realities of practice. Unlike Beecher, however, I realized that a "conscientious, compassionate [and] responsible investigator" could only come into being, as I have just suggested, after the value conflicts inherent in research are clarified and choices are made about the priorities to be given to competing values. Early in my work I did not appreciate the primacy I now wish to assign to respect for persons.

In the introduction to my book Experimentation with Human Beings I wrote: "When human beings become the subjects of experimentation ... tensions arise between two values basic to Western society: freedom of scientific inquiry and protection of individual inviolability.... At the heart of this [value] conflict lies an age-old question: When may a society, actively or by acquiescence, expose some of its members to harm in order to seek benefits for them, for others, or for society as a whole?" (p. 1). My question assumed, at least implicitly, both the necessity of conducting human research and die inevitability of harm; it asked only when society may "expose some of its members to harm."

Today, I want to put this question more pointedly. When, if ever, is it justified to use human beings as subjects for research, considering that they also serve as means for the ends of others? My new question seeks to emphasize that the oft-invoked moral right to engage in human experimentation is itself in need of a thoroughgoing examination, for that right which finds its justification in the need to advance the frontiers of knowledge can all too readily obliterate "the deepest matters of our morality" by the ways in which we use human beings for our own purposes. In pursuing the question of a fight to engage in human experimentation, I shall touch on only two issues: (1) the nature and quality of the initial encounter between physician-investigators and patient-subjects; and (2) the necessity for an explicit societal mandate to conduct research.

The Invitation to Participate in Research

Whenever human subjects of research serve the ends of others, the morality of protecting their physical integrity, which continues to preoccupy the thinking of physician-investigators, is not the central issue. It is, first of all, the morality with which the invitation to participation in research is extended so that the rights of subjects to be secure in their person and body remain sacrosanct. That fundamental requirement is viewed too dismissively as an impediment to the conduct of research. In 1972 I believed that the requirement of informed consent could serve as "the primary means for implementing the abstract notion of self-determination" and that it expressed "society's desire to respect each individual's autonomy and his right to make choices concerning his life."[7] I was then all too hopeful that the sentiments contained in both assertions would soon guide the conduct of human experimentation. This has not happened.

Let me begin with informed consent and briefly go back first to 1947, when the requirement of consent for participation in research was for the first time (some exceptions to the contrary notwithstanding)[8] compellingly argued by the Allied Military Tribunal. In promulgating the Nuremberg Code, the tribunal set forth as its first principle that in the conduct of research "the voluntary consent of the human subject is absolutely essential."[9] Beecher demurred. Even though his comments on the code in his 1958 Experimentation in Man disclaimed any "attack on the principle of consent," he concluded that "the |obvious' matter of consent is not so easy to live up to as it sounds" and that it is, therefore, far better to rely on the compassion of the investigator (p. 58). In his 1966 article he modified his position somewhat: While consent in any fully informed sense may not be obtainable, "it is absolutely essential to strive for it" (p. 1360). Other physician-investigators remained much more adamant in their assertion that adherence to the Nuremberg Code's first principle is too inhospitable to the conduct of research. Of course, the critics were correct in pointing out that the Nuremberg Code made no provisions for research with children or the mentally disabled. The Nuremberg Code is limited, as are my comments throughout this article, to research with persons who have the capacity to consent. Clearly, special provisions need to be drafted for those incapable of giving consent.

Disclosure practices changed, at least in form, when consent was replaced by informed consent. Yet, as I have repeatedly argued elsewhere, this doctrine, borrowed from the law of torts, cannot readily be transplanted into therapeutic settings, and surely not into research settings, without a prior thoroughgoing reappraisal as to whether the functions it is to serve should be the same for purposes of law, therapy, and research.[10]

The common law judges who promulgated the doctrine limited their task to articulating new and more stringent standards of liability whenever physicians withheld information that the judges believed was owed to patients in light of the harm that the spectacular advances in medical technology could inflict. Shaped and circumscribed by legal assumptions about the objectives of the laws of evidence and negligence, and by economic philosophies as to who should assume the financial burdens for medical injuries sustained by patients, the doctrine was most limited in scope, designed to specify those minimal disclosure obligations that physicians must fulfill to escape legal liability for alleged nondisclosures. The legal doctrine of informed consent was not designed to serve as a medical blueprint for the interaction between physicians and patients or investigators and subjects.

A broader, insufficiently recognized, and surely contested assumption, however, underlies the doctrine: the idea of informed consent.[11] It suggests that physicians and patients, investigators and subjects must make decisions jointly, with patients' and subjects' choices ultimately receiving utmost respect. To translate that idea into reality is a difficult undertaking requiring careful study and explication that has barely begun. Without implementation of this idea, informed consent in the sense it is now being adhered to will remain a charade.

The informed consent requirements set forth in the federal regulations on human research[12] do not adequately address the moral issues that deserve consideration whenever human beings serve as means for the ends of others. The drafters of the regulations should have been aware that physician-investigators would view the informed consent requirements, despite their greater specificity, as similar in intent to what they were used to complying with in clinical practice. This problem becomes even more acute in light of the radical transformation of medical practice since World War II. The astronomical increase in clinical research has, in practice, not led to a clear demarcation between therapy and research, bioethical theories notwithstanding. This vital distinction remains blurred when physician-investigators view subjects as patients, and then believe that patients' interests and not science's are being served by participation in the randomized clinical trials that are so commonly conducted in today's world; or when subjects are insufficiently apprised that attention to their individual needs is compromised by the need to comply with the rigid and impersonal methodology of a research protocol.

The drafters should have explicitly warned investigators that taking informed consent seriously in research negotiations requires them to spend considerable time with prospective patient-subjects. They should have provided explicit instructions on the length to which investigators must go in explaining themselves and their intentions so that patient-subjects will know what is being asked of them. Respect for subjects' human rights dictates that they appreciate that the decision to participate in research entails making a gift for the sake of others.

The drafters of the federal regulations needed to be more punctilious in their promulgations because they conferred on physicians a societal mandate to engage in clinical research on a scale that Hippocratic commandments never envisioned when they instructed doctors to "follow that system of regimen which, according to my ability and judgment, I consider for the benefit of my patients."

I now believe that meaningful informed consent doctrine for clinical research cannot be formulated without committing oneself to a theoretical position, Kass's warning about the snares of abstraction notwithstanding. Mine is this: whenever we use human subjects for the sake of others, using them as means for our ends, the principle of autonomy alone must guide such practices. I hasten to add that I have always used autonomy in James Childress's sense of "respect for autonomy" that "obligates us to respect the autonomous choices and actions of others."[13]

I argued that point in my book The Silent World of Doctor and Patient:

Respect for psychological autonomy requires that both parties pay caring attention to their capacities and incapacities for self-determination by supporting and enhancing their real, though precarious, endowment for reflective thought. In conversation with one another, patients may uncover mistaken notions [and] physicians may uncover [some of] their unconscious preferences and biases.... Without conversation, individual self-determination can become compromised by condemning physicians and patients to the isolation of solitary decision making, which can only contribute to abandoning patients prematurely to an ill-considered fate.

Even though choices are influenced by psychological considerations, it is one thing to appreciate that fact and quite another to interfere with choice on die basis of speculations, or even evidence, about underlying psychological reasons.... Short of substantial evidence of incompetence, choices deserve to be honored.[14]

Childress qualified his position somewhat when he wrote that "respect for autonomy [as] guiding science, medicine, and health care ... cannot be assigned unqualified preeminence." A careful reading, however, makes it clear that he only meant to convey that "other important moral considerations ... must be met prior to soliciting the potential subject's consent to participate - e.g., research design, probability of success, risk-benefit ratio, and selection of subjects." Ultimately he stated unequivocally that "if researchers do not receive the potential subject's voluntary, informed consent, they may not enlist that subject."[15]

I hope that Daniel Callahan will accept my views on autonomy as a moral good, not a moral obsession. What I have talked about so far does not undermine the importance he ascribes to fostering altruism or obligations to the community; for he cautioned his readers that his remarks on obligations toward others should not

be construed as a plea to either jettison or sharply devaluate autonomy as a value and an ideal. That is not my purpose. We live in a world too prone to tyranny, and in the company of a medicine too prone to forget that patients are persons, to want that outcome. The drive for autonomy that was the major moral mark of the 1960s and 1970s in medical ethics was indispensable. It brought patients into a full partnership with physicians in their medical care. There can be no return to those good old days that understood doctors to be good old boys who could work out moral problems among themselves in the locker room.[16]

Yet, that "full partnership" is a precarious one, as Callahan recognized in the same article: " [W]e may well grant that the notion of autonomy, especially patient autonomy, has hardly become triumphant in the daily life of medicine " (p. 40).

My plea for respect for autonomy, or better, for respect for persons, is based on three premises: that it is absolutely essential in situations where patient-subjects are asked to serve as means for others' ends; that it has never been truly tried out; and, since it is "good as a bodyguard against moral bullies,"[17] that it can protect patient-subjects from the moral bullying of investigators too invested in the morality of their scientific pursuits.

The Societal Mandate

Of course, society may decide to grant scientists a mandate to compromise individual autonomy by permitting them to balance it against the need to advance science for the benefit of mankind. Indeed, the federal regulations confer such a mandate on physician-investigators. This mandate, however, has not been subjected to an intense scrutiny and public debate about the limits to be imposed on the prerogatives of scientists to use human beings for society's sake. Such a debate deserves to be carried on with the same intensity as the one that has repeatedly taken place on the question whether it is preferable to rely on a military draft or a volunteer army to protect citizens' and society's interests.

My reading of the Congressional Record, whenever either proposed regulations of research or budgetary allocations for research are debated, leaves me with the impression that Congress is confused about the boundaries between research and practice; that it has, therefore, insufficiently faced up to the fact that the practice of medicine and the conduct of research are different enterprises. The mandate conferred on physicians at the beginning of this century to practice medicine with few constraints cannot be readily transported into research settings. Policymakers must confront their responsibility to formulate a distinctly separate societal mandate for the conduct of research that specifies the lengths to which a democratic society like ours can go in compromising citizen-subjects' rights to autonomy and physical integrity for the sake of medical science. We have been all too willing in our longing to conquer disease and death, as Edmond Cahn once put it, "to possess the end and yet not be responsible for the means, to grasp the fruit while disavowing the tree, to escape being told the cost, until someone else has paid it irrevocably."[18]

Twenty years ago I urged that we resist such a resolution. In the final report of the ad hoc advisory panel of the Tuskegee syphilis study I recommended, and the panel concurred, that Congress establish a permanent body, a National Human Investigation Board (NHIB), with the authority to regulate at least all federally supported research involving human subjects.[19] Among its functions would be the responsibility to formulate research policies, to promulgate procedures for the review of research decisions and their consequences, and to publish important IRB and NHIB decisions.

Senator Edward Kennedy incorporated that proposal in a bill submitted to the Senate. A major reason why his bill was never enacted may have been the Senate's reluctance to expose to public view the value conflicts inherent in the conduct of research. Had the Senate seriously debated the bill, it would have been forced to consider when, if ever, inadequately informed subjects can serve as means to society's and science's ends.

I believed then, as I do now, that the rejection of an NHIB was not just a mistake but a subterfuge to avoid giving greater public visibility to the decisions made in the conduct of human experimentation. Current practices do not provide for institutional review committees' publication of, or unencumbered access to, such decisions. A low level of visibility not only hampers efforts to evaluate and learn from attempts to resolve the complex problems of human research but also precludes the public at large from reacting to what is being done for the sake of the advancement of science.

Local IRBs cannot assume the functions that a National Human Investigation Board should serve. Existing federal regulations, as is true for many statutory enactments, are too vague and broad in scope; they require constant interpretation, refinement, and revision. Such tasks are beyond the capacity and perhaps authority of IRBs. Moreover, as George Annas has observed, "IRBs as currently constituted do not protect research subjects but rather protect the institution and the institution's investigator."[20] While this is perhaps too sweeping an indictment, there is considerable truth to his allegation. The majority of IRB members are on the faculty of the institutions to which investigators belong, and they share similar interests and objectives. Thus, particularly in the murky area of informed consent, it is unlikely that members of IRBs will hold investigators to a standard of disclosure and consent that would protect the subjects of research if doing so would place impediments on the conduct of research and, in turn, affect the professional and personal pursuits of their colleagues in decisive ways.

Respect for Persons

Throughout this essay I have tried to make it clear that in the pursuit of scientific progress we have not taken the human rights of research subjects as seriously as they deserve to be taken. The idea that human beings possess human rights is of such recent origin that the contours of such rights remain ill defined. It is an idea, however, that since World War 11 has captured the imagination of the world community, as the many United Nations' resolutions on human rights attest.

It is important to remember that at the dawn of bioethics, respect for human rights, autonomy, self-determination was foremost in the minds of the philosophers, theologians, and the many others who created this new discipline. Their contributions remain an important legacy. Like the judges who promulgated the informed consent doctrine, these philosophers and theologians, when they entered the scene, were astonished by the low priority physicians accorded to autonomy. Twenty years later respect for the principle of autonomy is once again going out of favor, and it is time to be astonished once again about the principle's short life.

To conclude, my initial interest in the study of human experimentation was shaped by my own practices and what I had read about the practices of others. Beecher's work, even more, was shaped by what he had observed about his research and that of his colleagues. After reflecting about where we began and where we now are, I want to argue more uncompromisingly then I ever have done that respect for autonomy and self-determination in clinical research, whenever human beings serve as means to others' ends, should be a binding commitment, except under the most exceptional and well-defined circumstances, and then only with societal approval.

Perhaps I would put this somewhat differently if I could share David Rothman's optimism that "the record since 1966 ... makes a convincing case for a fundamental transformation [of medical decision making in] the conduct of research. [T]he experiments that Henry Beecher described could not now occur."[21] They do occur now, though Rothman is correct that a Tuskegee syphilis study would not now pass IRB scrutiny. Tuskegees, however, have always been rare events in the annals of medical research; mini-Tuskegees are still all too prevalent. John Fletcher's concerns in one of the earliest volumes of The Hastings Center remain concerns in 1993. His conclusion then continues to ring true today: "Now that the period of concern about the principle of informed consent has crested, and lest this concern be found to be mere sentimentality, more thorough steps to institutionalize and embody the value of personhood in medical research are required."[22]

Henry Beecher's vision of the ethics that should govern research still eludes us. Kass put it perhaps too pessimistically when, in reflecting on the contemporary state of bioethics, he observed that "though originally intended to improve our deeds, the reigning practice of ethics, if truth be told, has, at best, improved our speech."[23] Yet he is correct that improving speech alone does not suffice. We must remember that concerns over conduct brought us into bioethics, and improving conduct remains our ethical task. This task was Beecher's intent, and that is why he wrote "Ethics and Clinical Research," even though he knew that in doing so he would infuriate many of his colleagues. The greatest tribute we can pay to this man of remarkable moral courage is to build on the legacy he has left us.

"Ethics and Clinical Research"

Human experimentation since World War II has created some difficult problem with the increasing employment of patients as experimental subjects when 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. Evidence is at hand that many of the patients in the examples to follow never had the risk satisfactorily explained to them, and it seems obvious that further hundreds have not known that they were the subjects of an experiment although grave consequences have been suffered as a direct result of experiments described here. There is a belief prevalent in some sophisticated circles that attention to these matters would "block progress." But according to Pope Pius XII, "... science is not the highest value to which all other orders of values ... should be subordinated."

I am aware that these are troubling charges. They have grown out of troubling practices. They can be documented, as I propose to do, by examples from leading medical schools, university hospitals, private hospitals, governmental military departments (the Army, the Navy and the Air Force), governmental institutes (the National Institutes of Health), Veterans Administration hospitals and industry. The basis for the charges is broad.

I should like to affirm that American medicine is sound, and most progress in it soundly attained. There is, however, a reason for concern in certain areas, and I believe the type of activities to be mentioned will do great harm to medicine unless soon corrected. It will certainly be charged that any mention of these matters does a disservice to medicine, but not one so great, I believe, as a continuation of the practices to be cited.

There are a number of reasons why serious attention to the general problem is urgent.

Of transcendent importance is the enormous and continuing increase in available funds....

Taking into account the sound and increasing emphasis of recent years that experimentation in man must precede general application of new procedures in therapy, plus the great sums of money available, there is reason to fear that these requirement and these resources may be greater than the supply of responsible investigators. All this heightens the problems under discussion.

Medical schools and university hospitals are increasingly dominated by investigators. Every young man knows that he will never be promoted to a tenure post, to a Professorship in a major medical school, unless he has proved himself as an investigator....

In addition to the foregoing three practical points there are others that Sir Robert Platt has pointed out: a general awakening of social conscience; greater power for good or harm in new remedies, new operations and new investigative procedures than was formerly the case; new methods of preventive treatment with their advantages and dangers that are now applied to communities as a whole as well as to individuals, with multiplication of the possibilities for injury; medical science has shown how valuable human experimentation can be in solving problems of disease and its treatment; one can therefore anticipate an increase in experimentation; and the newly develoved concept of clinical research as a profession (for example, clinical pharmacology) - and this, of course, can lead to unfortunate separation between the interests of science and the interests of the patient.

All so-called codes are based on the bland assumption that meaningful or informed consent is readily available for the asking. As pointed out elsewhere, this is very often not the case. Consent in any fully informed sense may not be obtainable. Nevertheless, except, possibly, in the most trivial situations, it remains a goal toward which one must strive for sociologic, ethical and clear-cut legal reasons. There is no choice in the matter.

If suitably approached, patients will accede, on the basis of trust, to about any request their physician may make. At the same time, every experienced clinician investigator knows that patients will often submit to inconvenience and some discomfort, if they do not last very long, but the usual patient will never agree to jeopardize seriously his health or his life for the sake of "science."

In only 2 of the 50 examples originally compiled for this study was consent mentioned. Actually, it should be emphasized in all cases for obvious moral and legal reasons, but it would be unrealistic to place much dependence on it. In any precise sense statements regarding consent are meaningless unless one knows how fully the patient was informed of all risks, and if these are not known, that fact should also be made clear. A far more dependable safeguard than consent is the presence of a truly responsible investigator.

The ethical approach to experimentation in man has several components; two are more important than the others, the first being informed consent. The difficulty of obtaining this is discussed in detail. But it is absolutely essential to strive for it for moral, sociologic and legal reasons. The statement that consent has been obtained has little meaning unless the subject or his guardian is capable of understanding what is to be undertaken and unless all hazards are made clear. If these are not known this, too, should be stated. In such a situation the subject at least knows that he is to be a participant in an experiment. Secondly, there is the more reliable safeguard provided by the presence of an intelligent, informed, conscientious, compassionate, responsible investigator.

Ordinary Patients will not knowingly risk their health or their life for the sake of "science." Every experienced clinician investigator knows this. When such risks are taken and a considerable number of patients are involved, it may be assumed that informed consent has not been obtained in all cases.

The gain anticipated from an experiment must be commensurate with the risk involved.

An experiment is ethical or not at its inception; it does not become ethical post hoc - ends do not justify means. There is no ethical distinction between ends and means.

In the Publication of experimental results it must be made unmistakably clear that the proprieties have been observed. It is debatable whether data obtained unethically should be published even with stern editorial comment.

References

[1.] Henry K. Beecher, "Ethics and Clinical Research," NEJM 274 (1966): 1354-60. [2.] Trials of War Criminals before the Nuremberg Military Tribunal, volume 2, The Medical Case (Washington, D.C.: U.S. Government Printing Office, 1948), p. 183. [3.] Henry K. Beecher, Experimentation in Man (Springfield, Ill.: Charles C. Thomas, 1958), p. 4. [4.] Natanson v. Kline, 350 P. 2d 1093 (Kan. 1960). [5.] Jay, Katz (with the assistance of Alexander M. Capron and Eleanor S. Glass), Experimentation with Human Beings (New York: The Free Press, 1972), p. 4. [6.] Leon Kass, "Practicing Ethics: Where's the Action?" Hastings Center Report 20, no. 1 (1990): 5-12, at 7. [7.] Katz, Experimentation with Human Beings, pp. 521, 524. [8.] See Michael A. Grodin, "Historical Origins of the Nuremberg Code," in The Nazi Doctors and the Nuremberg Code, ed. George J. Annas and Michael A. Grodin (New York: Oxford University Press, 1992), pp. 127-32. [9.] Trials of War Criminals before the Nuremberg Military Tribunal, vol. 2, p. 181. [10.] Jay Katz, "Duty and Caring in the Age of Informed Consent: Unlocking Peabody's Secret," Humane Medicine 8 (1992): 187-97. [11.] Katz, "Duty and Caring," pp. 188-89. [12.] Department of Health and Human Services, Rules and Regulations 45 CFR 46, [Section] 14.116, 1983. [13.] James F. Childress, "The Place of Autonomy in Bioethics, Hastings Center Report 20, no. 1 (1990): 12-17, [14.] Jay Katz, The Silent World of Doctor and Patient (New York: The Free Press, 1984), pp. 128, 112-13. [15.] Childress, "The Place of Autonomy in Bioethics," p. 16. [16.] Daniel Callahan, "Autonomy: A Moral Good, Not a Moral Obsession," Hastings Center Report 14, no. 5 (1984): 40-42, at 42. [17.] Callahan, "Autonomy," p. 42. [18.] Edmond Cahn, "Drug Experiments and the Public Conscience," in Drugs in Our Society, ed. Paul Talalay (Baltimore: The Johns Hopkins Press, 1964), p. 260. [19.] Tuskegee Syphilis Study Ad Hoc Advisory Panel Final Report (Washington, D.C.: U.S. Government Printing Office, 1973). [20.] George J. Annas, Judging Medicine (Clifton, N.J.: Humana Press, 1988), p. 331. [21.] David Rothman, Strangers at the Bedside (New York: Basic Books, 1991), p. 251. [22.] John Fletcher, "Realities of Patient Consent to Medical Research," Hastings Center Studies 1, no. 1 (1973): 39-49, at 49. [23.] Kass, "Where Is the Action?" p. 8.
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