Ethical Issues
Report on the Lasker Forum on Ethical Challenges in Biomedical Research & Practice
May 14 - 16, 2003
Acknowledgments
This report grows out of a conference in May, 2003 — the Forum on Ethical Challenges in Biomedical Research & Practice — initiated and sponsored by the Mary Woodward Lasker Charitable Trust, with additional and very welcome support from the Walter and Elise Haas Fund, the Robert Wood Johnson Foundation, the Greenwall Foundation, and the American Association for the Advancement of Science. Together, these non-profit organizations contributed generously to the exploration of a topic of vital interest to medical, patient, and policy communities.
The Lasker Trust expresses its gratitude to the co-chairs of the Forum, Donald Kennedy and Harold Shapiro, who organized the event and who were generous with their time, insights, and wisdom. Dr. Kennedy, supported by his capable assistant Penny Warfield, authored this Forum report and was a contributing editor to the case studies and omnipresent counselor. Special thanks are extended to Margaret Eaton for the original writing and intellectual contributions from which the case studies emerged. The Lasker Trust also wishes to express appreciation to Mark Frankel, with the Association for the Advancement of Science (AAAS) for collaboration with the Trust on the Forum arrangements. Thanks as well to Marty Krasney, the Forum's coordinator, who provided valuable perspectives and advice; and to Ticien Sassoubre for editing comments in the case study material. Finally, the Trust thanks the participants who attended the Forum; their thoughtful insights and comments form the basis for the discussion section of the case study materials. Several of the participants, and most notably Hank Greely, Judy Illes, and Simon Whitney, provided extra help in recording the discussion exchanges.
FORUM REPORT
By Donald Kennedy
Forword
A lively, mixed group of physicians, surgeons, lawyers, bioethicists, journalists and health policy experts came together in Washington in May of 2003 at the invitation of the Mary Woodard Lasker Charitable Trust. The stated purpose of the Forum was to examine some of the pressing ethical and legal issues that are emerging from recent progress in biomedical research and clinical practice. The Lasker principals were primarily interested in a number of problems in the adjoining areas of innovative clinical practice and more formal research, between which lies a gray area in which the innovation could either be considered research (which is formally regulated) or medical practice (which is governed by professional and malpractice standards). The objective of the forum was to map the terrain by illuminating some problem areas along this divide. The project intended to identify: (a) how medical innovations both benefit and fail us, (b) gaps in prevailing practices or regulatory oversight, if any; and (c) challenges posed by innovation to the ethical structure of medical practice. The Forum was conducted through the analysis of the four original hypothetical cases, developed and circulated in advance and explored at the meeting by multidisciplinary working groups. Plenary discussions then focused on common themes that emerged from case study analysis.
As the Lasker Forum was being planned, medical ethics was to be the focus, and some had urged that we consider centering the discussion on some of the well-trodden pathways in biomedical ethics: the long-running debate about stem cells; the question of human cloning; the fine line between treatment and enhancement. The planners chose to focus instead on a broader issue — the process of innovation and the circumstances under which it takes place in the real world. The central problem is perhaps best exemplified by the following circumstance. A skillful physician-scientist encounters a patient with an unexpectedly challenging life-threatening condition. Treatments meeting the usual medical "standard of care" have proved unavailing, but the physician — from animal experiments conducted in his laboratory over several years — believes that a different kind of intervention could work. The novel procedure is applied — and the patient improves!
Most practitioners and patients would applaud the physician for going forward — at least the first time. The level of approval might depend, of course, on just how far out the new procedure was with respect to the standard of care. But in the interest of the patient, most practitioners and most organizations (professional societies, hospital boards, and the like) believe in innovative medicine that preserves health and saves lives.
At some point, however, a question arises about whether an innovation is regarded as a practice variation lying clearly within the scope of the physician's initiative, or as something else. The "something else" would be research: a clinical innovation that is conducted under a planned protocol, with its outcome carefully recorded, and subject to a highly-evolved panoply of oversight and rules designed to protect patients (read: human subjects) from the adverse consequences of premature technology and/or over-enthusiastic recruitment. That innovation sometimes proceeds with little oversight, but at other times it is called research and made subject to extensive controls is something of a paradox. The Forum Co-Chair Harold Shapiro perhaps best captured the distinction in this way: "Why is it that we regulate only when we expect to learn something?"
As the Lasker attendees explored this "gray area" between innovative medical practice and research, some differences emerged — many of them represented in the pages of this casebook. Leading clinical practitioners were clearly worried about their patients' welfare, but equally concerned that ethical considerations might lead to a regulatory environment that would stifle innovation and restrict medical progress. Distinguished ethicists sometimes saw the reputations of distinguished physicians, and the confidence they display, as inducements to patients to ignore risks. These discussions were lively, and although they did not produce a clear consensus, they were useful in sketching a map for some unfamiliar terrain.
Just before the Forum, and again several months after it ended, the New Yorker published articles that fortuitously comprise a pair of intellectual bookends for the discussions of medical innovation that took place there. Both articles were authored by physicians who are also superb medical writers. The first, by Antul Gawande [1], was a long biographical sketch of an influential Harvard physician, Francis Moore, who was launched into a remarkable surgical career by his experience (as a young resident) in treating the burn victims of the famous 1942 Coconut Grove fire. The second, by Jerome Groopman [2], was built around long interviews with the actor Christopher Reeve, who as nearly everyone now knows was paralyzed by a cervical dislocation experienced during an equestrian competition. The interplay between medical aggressiveness and risk on the one hand, and caution and patient protection on the other, forms a dramatic focus in both these stories.
The young Dr. Moore (popular, and widely known around Harvard in those days as "Franny Moore") was about as medically venturesome as it gets. He became chairman of surgery at Harvard's Peter Bent Brigham Hospital at 34, and made a series of extraordinary research discoveries. As a clinician, he could be counted on to deploy and then to advocate procedures that went beyond the "standard of care" boundary, and he became, at least around Boston, a kind of emblem for aggressive practice. Some of Moore's patients' lives were saved with dramatic new procedures that later became widely adopted. Other patients died during Moore's attempts to save them — risks Moore was willing to take in what he believed to be their best interest. But later in his career, after a series of spectacularly failed liver transplants, Moore had a conversion; as Gawande put it, "he never experimented with a major new therapy in human beings again." Instead, he became an advocate for perfecting all new procedures on animals before applying them in the care of human patients, and he authored a series of studies evaluating the outcomes of innovative surgical procedures. In the mid-arc of his career, Moore transformed himself from an aggressive young surgeon into a cautious elder who promoted evaluation of new procedures before adopting them into practice. At the end of his account, Gawande — himself a young surgeon — asks himself which Moore he prefers — and inclines to the young Moore.
Groopman's account of Reeve's effort is dramatic. The actor, equipped with high intelligence, a powerful personality, and a huge incentive to get better, has made a career of persuading scientists and doctors to get on with it. He is dissatisfied with the cautious, conventional medical wisdom about the improbability of neural regeneration, and impatient whenever he encounters any unwillingness to try new methods. Reeve says, "I don't want reckless physicians, but I don't want fearful ones either." At some medical meetings, he annoys his audiences by criticizing medical caution and pushing researchers to do more. One could say, of course, that Reeve's functional impairment, in addition to providing an incentive for cure, also encourages him to be overly tolerant of risk. Given the choice, it is fairly plain that he, too, would have preferred the young Franny Moore. How the author, himself a physician, would have voted is much less clear. Nor would a vote of the Lasker participants have produced a clear preference. This is, after all, the Old Dilemma in medical innovation.
In the end, the ethical challenge in this area comes to rest in a familiar place. It is one with which I became familiar as Commissioner of the Food and Drug Administration in the late 1970s. On the one hand, new technologies and new procedures offer the possibility of dramatic short-term benefit — even rescue — for the patient under treatment. On the other, premature introduction of those technologies or procedures presents real risks of iatrogenic illness; they may damage more than they cure. So the purpose of regulation, whether in the form of patient protection or of restraints on the approval of new drugs and devices, is to slow technology deployment until it has been thoroughly examined for risk. That approach, of course, can lead to lively arguments. I was often asked, in a challenging way, whether I didn't think that the new drug approval process at FDA slowed the progress of innovation. I would answer "of course." Regulation seeks to find a public policy position that balances the costs of premature introduction against the costs of foregone innovation. Those responsible for health policy constantly face a crossfire of charges: that they are not doing enough to protect patients, and that they are doing too much harm to patients, by forestalling innovation. That, too, is the Old Dilemma, and it will be with us some time.
Each of the four cases in this casebook explores this Old Dilemma, each in a different way with a different kind of medical practice — off-label drug use, innovative surgery, assisted reproductive technologies, and neuroimaging. The discussions that followed the presentation of these cases were lively, and sometimes entailed strong disagreements about the circumstances under which society would be justified in regulating some aspect of the physician's work. Some of the scenarios may be judged futuristic, but the rate of medical progress surely justifies the exercise of some imagination in attempting to meet problems before they arise. One thing seems certain: however dramatic the progress, and however the circumstance of medical intervention may change, the Old Dilemma will still be with us.
Preface
The Lasker Forum, attended by sixty-seven participants drawn from various fields including bioethics, basic research, clinical practice, health policy, and law, considered a number of problems in the adjoining areas of innovative clinical practice and more formal and often regulated biomedical research protocols using human subjects. The objective was to examine the extent to which physicians, either in academic medical centers or in private practice, treat patients in innovative ways that are generally intended to benefit the individual patient but that may have wide-ranging implications for medical practice in general — often but not always for the better. Our hope was to identify dilemmas and ethical challenges in this area of clinical innovation that face those who practice and those responsible for policies that might govern it. [3]
The Forum was designed to assess whether there are special issues in this domain that should be considered in more depth. It was conducted through the analysis of four hypothetical cases, developed and circulated in advance and explored by multidisciplinary working groups.
1. Assisted Reproductive Technology. An innovative practitioner in a successful clinic has made improvements in the in vitro culture medium, and confronts literature identifying putative risks to the procedure. This case explores disclosure issues with respect to various risks, and privacy and legal matters involved with embryos not used in the implantation procedure.
2. Microsurgery. A cardiac surgeon has developed a device and associated technique for minimizing the invasiveness of heart surgery. There is involvement of a device firm in which he has a financial interest. Issues involving patient selection, disclosure, and conflict of interest were raised in this case.
3. Off-Label Drug Prescribing. An experienced endocrinologist has consulted for a well-known drug firm in the development of a drug useful in certain adult-onset diabetes cases. In an early trial it appears to be useful in weight control; the endocrinologist urges, but the company rejects, new studies to prove efficacy. Questions are raised about the doctor's potential conflicts and about risk-benefit balancing in his and the company's actions.
4. Magnetic Resonance Imaging. A neuropsychiatric clinic employs fMRI analysis to examining brain patterns in a youth with a personality disorder. The case raises issues about the appropriate use of disturbing visual scenarios and imaging studies in diagnosis, and questions about the subsequent use of the data in legal proceedings.
In each of these cases, participants encountered similar challenges in how best to balance innovation and progress with the interests of individuals. These led to the identification of some themes that proved common to all. Plenary discussions then focused on those themes. The following account begins with an introduction borrowed heavily from Co-Chair Harold Shapiro's keynote address on the Forum's first morning.
Introduction
Liberal democracies have a built-in commitment to change and improvement. Thus innovation has strong value in nations like the United States; but it carries with it, as Shapiro points out, a certain level of moral anxiety. It also imposes a moral duty: because innovation produces both progress and risks, society and its innovators owe some protection to those (patients, clients, consumers, investors, future generations) who may be exposed to unexpected hurts or external costs.
In the environment of health technology and biomedical research, the rapid pace of change continues to alter the landscape in which the rights of patients and others must be evaluated. These changes have shaped the contemporary environment in which innovative medicine and research are practiced — yet the culture and the rules within which we undertake them have remained relatively unaltered. The environmental changes are summarized in the following section to provide context for the Forum's main task.
The Complexity of the Environment
The rapid progress of basic science and clinical technology has brought about a new convergence of institutions. Universities, practitioners, patients, hospitals, for-profit companies, the judiciary and other government agencies are all actors in the contemporary arena in which health is being advanced. None of this is new, surely; but universities and companies now seek more financial return for health investments, and government has a new impetus for controlling costs. Thus new opportunities arise for conflicting interests and competing values.
Patients today come to each medical encounter with many more independent sources of information and sometimes misinformation than ever before: the Internet and the media provide the public access to increasing information about drugs, devices, and other health technologies. As a consequence, patients may bring more power to the patient/clinician relationship; on the other hand, the authority automatically accorded to clinicians through prestige and professional stature may be much desired by the patient but also tilt the power relationship in the opposite direction.
The health care environment involves multiple jurisdictions: state and federal agencies involved with regulation, funding, or reimbursement; professional societies and health insurers (themselves operating under state and/or federal rules) may all be involved. Increasingly, the courts play a significant role. These different jurisdictions and points of control sometimes yield conflicting or inconsistent directions about the way in which clinical innovation is to be managed. In addition, the media now devote increased coverage to biomedical innovation, generating enhanced levels of public awareness, concern, and — sometimes — hope. Finally, the pace of progress in basic science and in medical technology has been extraordinarily rapid. All these changes may have stressed the capacity of social responses to keep up. Finally, the multiplicity of parties and the complexity of the health care system have come to require special mechanisms for allocating the responsibility for patient protection.
The Intersection Between Research and Innovative Practice
There is a broad area in which innovative medical practice — the variations in treatment and procedural intervention that good clinicians regularly deploy — intersects with more formal research in which clinical researchers design studies to obtain knowledge while at the same time claiming to improve the care of those individual patients. Innovative practice — especially in mid-procedure — is regulated primarily by the conscience, behavior and talent of the individual physician, by various forms of collegial oversight — or, sometimes, by fear of litigation. Research involving human subjects entails a whole panoply of oversight arrangements laid on by society. The border between the two is not always clearly defined, and in our Forum discussion it was at first called a "gray zone." That term ignores important internal subdivisions within the domain. On the other hand, it does move us away from an artificial separation, enhanced by the "Common Rule," in which a distinction is made between what is called research and therefore requires more regulatory oversight, and what is called "care" and is thought to require little or none. That leads to the rather wry characterization: "we regulate only when we expect to learn something."
The intersection on which the Forum focused might best be called that aspect of clinical innovation or exploratory practice that involves a departure from the standard of care, and that may or may not increase the physician's duty to consider the ethical implications of his or her treatment. Under these circumstances, the physician is undertaking two moral duties: to provide the best care for the patient, and to record and analyze the results so as to expand the knowledge base available for the treatment of others. At the same time, the physician may be enhancing his or her own skills to advance in the professional hierarchy, or seeking commercial benefits in ways that may be entirely appropriate but could raise perceptions of conflict of interest.
The case studies examined by the Lasker working groups attempted to analyze some areas in which we might learn from such innovative practices. In drug prescribing, for example, many knowledgeable clinicians prescribe drugs for indications beyond those specified in the label. This legal practice is often a source of medical benefit, but may present new risks. In developing technologies for assisting reproduction through in vitro fertilization, changes in culture medium or implantation procedure may be made by physicians seeking to improve the success of the procedure. In the development of cardiovascular devices, marginal changes (away from "substantial equivalence" to pre-existing devices) probably take place fairly frequently; more important still would be departures in the procedures themselves, quite apart from the devices. And new brain imaging techniques might be combined with psychotherapeutic intervention in ways not envisioned by contemporary practitioners. Studies of examples like these helped the working groups to grapple with the often-slippery distinction between "research" and "innovative practice." As the working groups came together, three or four cross-cutting themes emerged. These may shed some light on how society might approach ethical issues that may arise in innovative medical practice.
Thresholds and Models of Oversight
Three rationales would appear to underlie the desirability of ethical oversight in innovative practice. First, society's expectation is that the health and other interests of patients should be protected, as they usually are. Second, society wants to promote thoughtful innovative practice and good research. And finally, whatever custom or structure is adopted should expand the public's confidence and trust in medical research and in the quality of clinical practice. In setting thresholds for oversight, all of the considerations ought to be centered on the well being of patients or, in some cases, of those patients who will come after them. These will include the degree of risk associated with the innovative procedure, and its degree of departure from existing norms, like standard of care — including the adequacy of the knowledge that underpins the risk estimate. The quality of evidence dealing with the new procedure, including the experience of the practitioner with closely related forms of practice, will also matter. Other aspects of the threshold determination would focus on the investigator. Intent matters: is the motive primarily research, or does the procedure focus primarily or entirely on the welfare of this particular patient? What is the experience of the investigator in the new area? Are factors present that put the investigator in a conflict of interest situation? Finally, there is the setting: is it an environment in which substantial institutional support, human and infrastructure, is available? Are third party interests involved, and are there other complexities: intellectual property considerations, financial liabilities, and the like?
Some combination of these factors will enter a societal decision about whether oversight is or is not required — and if it is, whether it should be imposed before the innovation can first be introduced or only afterward, as in tissue or case review. Assuming that it is decided that oversight is necessary, what models are available? There are many potential alternatives: some depend on control of information: informed consent requirements, consumer protection, public education, and various accreditation mechanisms. Others depend on payment: requirements associated with public insurance coverage, and even research funding. Some involve self-regulation by the professions, through medical societies, specialty societies and boards, simple peer pressure, or controls put in place by institutions. Federal and state governments assert oversight through various devices: product approval requirements (FDA), state licensure, and a variety of other state and federal agencies. Finally, there is control through liability: medical malpractice, and product liability. The multiplicity of possible forms can allow some fine-tuning of oversight mechanisms, if any are needed, to fit diverse problems or situations.
In thinking about possible systems of oversight, the following considerations were emphasized. First, whatever is selected should work — that is, should both protect patients and be helpful in improving clinical practice. Second, whatever system is employed should, to the extent possible, make use of presently available systems and institutions — in addition to taking advantage of new and unused outlets — journals, databases, and other information tools. If the threshold for formal, a priori oversight is reached, then the basic requirement is that someone, or some institution, other than the investigator/practitioner be looking at the new technique in order to determine whether or not it should go forward. Finally, whatever oversight mechanism is selected ought to have a capacity for self-improvement; in other words, the knowledge gained from a successful departure should be retained and communicated so that others may benefit. Some Forum participants called this a "duty to learn."
Disclosure
A moral underpinning for all clinical encounters is the need to supply the patient with information about the motives and capacities of the physician and the risks and benefits of what is proposed. When the encounter involves only the usual standard of care, and thus is non-innovative, special systems of administrative oversight (beyond qualification and certification of the physician) are not required. In these situations, the obligation of the physician is to explain and to inform, for the patient's benefit. Disclosure should supply whatever information a reasonable patient would need to reach a decision about his or her treatment.
Where innovation is clearly present, the requirements for disclosure are likely to become more pressing, since the practices involved lack more formal validation. It may be important for the physician to acknowledge conflict of interest, for example in cases where there is a financial or other interest in the technology on the part of the physician or of the institution, or where the newness of the technique makes it important for the patient to learn something about the physician's experience with the procedure, and where he or she is on the learning curve. For certain kinds of technological or procedural innovations, there may be particular requirements. For example, if the physician is prescribing a drug for an indication beyond the one approved on the drug's label, the patient should know that this is being done, and have some information about the clinical experience with that drug for that purpose. In the case of assisted reproductive technology, disclosure needs to take account of long-range risks to the children who would result from a successful procedure. There may also be special requirements for disclosure where regulations exist about which patients are likely to know little. All of these features are fundamentally consistent with the spirit of informed consent.
Much of what should be said about disclosure applies to standard clinical engagements as well as those in which innovation is a feature. Its purposes are multiple. For the patient, it should enable more informed decision-making. Disclosure may also satisfy certain emotional needs allowing the patient to reach a level of comfort about a decision that may involve ambivalence or fear. Disclosure, it was emphasized, may be important for the physician as well as the patient, possibly giving the physician an opportunity to reconsider the wisdom of the procedure and to understand the patient's point of view.
Disclosure is not a straightforward venture. Many patients develop strong identification with their physicians, especially figures of high reputation. The encounter might be influenced by a referral from the patient's primary-care physician: "I'm referring you to Dr. Smith, who is absolutely the best in this field" — carrying the clear implication that the referral is based on Smith's experience with the particular technique involved. The well-known and heavily recommended physician may scrupulously communicate the "check list" of items to be disclosed, but the well-established credibility with which he arrives may persuade the patient to treat risks lightly. For this and other reasons, it may be desirable to involve an experienced third party in disclosure, and institutional oversight processes for dealing with innovative medical interventions sometimes consider such arrangements.
It was pointed out that the duty to disclose may not end with the interaction itself; new information about lingering risks can emerge from patients long after the treatment, or after new insights have been gained about the physiology underlying the disease. That implies a continuing obligation for physicians, who must keep track of delayed adverse reactions in those patients or those who have experienced similar treatment. Patients are also entitled to know how much personal time the physician is prepared to commit to the patient after the procedure. Finally, disclosure is an important activity, about which empirical knowledge is relatively sparse. Formal studies on the impacts of different styles and methods of disclosure on patient choice could improve our understanding of how best to fulfill this obligation.
It should be noted again that most of these considerations apply to disclosure about routine interventions as well as to the more innovative ones. But when there is a departure from the standard of care, the stakes are raised; disclosure practices become a more important challenge for the physician and the institution.
"Duty to Learn"
Where an innovative medical procedure is attempted, there is an expectation that the incremental risks to the patient associated with the departure from "standard of care" is balanced by two potential benefits, one to that patient as well as one to society through the possible improvement of practice. The ethical challenge for the physician is to structure the encounter so as to maximize knowledge while benefiting the patient who is receiving the novel therapy. This first duty of the physician and the system we have called the "duty to learn." The physician and the institution need to devise ways of responding to that duty; a successful innovation, if it is not disclosed to the community, can hardly fulfill the promise that society as well as the patient may benefit from the physician's skill. This duty is tempered by certain realities: some patients present problems so special that the physician's experience may add little or nothing to the knowledge commons.
The Common Rule incorporates a standard that gives physician intent a significant role in determining whether an intervention is practice or research. HIPAA and other regulations (including state laws) create formal requirements for interventions that meet the Common Rule definition. A question considered at some length in the Forum involved what kinds of physician obligations might be required of innovative procedures that do not meet that definition, yet still would be subject to the "duty to learn." In Formal, controlled clinical trials are clearly research, and subject to several forms of regulatory oversight. But there is a form of less formal, "fly-by" learning in which particular outcomes can be evaluated and communicated. In these cases, it is plain that some systematic data collection and analysis are necessary if effectiveness is to be evaluated fairly — but many practitioners lack the resources to make that possible. There was agreement that in general, more serious outcome analysis of that kind is desirable, that it may require adding new mechanisms to help individual physicians with the work, and that such evaluations should include cost effectiveness.
Summary and Outlook
The Forum set out to explore the geography of an area with uncertain dimensions. Despite consideration by many experienced and thoughtful individuals, it proved difficult to deliver guidance about specific situations or to define with any precision the circumstances where additional oversight is warranted. Much of what is good about the practice of medicine happens at the edge of what is certain — in other words, at the margins of the current standard of care. Some of this involves the small increments in procedure or treatment that good physicians regularly undertake. Some involve innovations so significant that they become part of formal research undertakings with a full panoply of institutional and governmental regulatory oversight.
There were differences of opinion — between practitioners and ethicists, and within each category — about the extent to which this area is presenting difficult challenges to clinicians, to the confidence of patients, or to public confidence in medical care. Although the discussions did not suggest significant opportunities for new mechanisms of formal regulation, there was agreement that more could be done to establish a wider understanding of the problems posed by innovation, and of the obligations physicians and their institutions owe where innovative practice is being done. This could include an examination of whether, and according to what model, some degree of more formal oversight should be established. Participants emphasized, however, that investigators and physicians can be encouraged to see good conduct in this area as part of their professional mission, as many specialty boards and academies do, rather than a set of obligations imposed by outsiders. A diverse set of special obligations about disclosure is attached to practice in this area. These require careful thought in the context of the special character of the procedure, and there is a need to study the effectiveness of different styles and modes of disclosure. Novel procedures may impose some added risk, raising the importance of their potential societal benefit and imposing what has been called a "duty to learn" — that is, to share information about outcome with the community of practice. Finally, since the area of concern involves medical practice, it was suggested that a great deal may be gained by modest additions to the curricula of medical schools regarding research design and the analysis of evidence. At the very least it would assist practitioners in understanding when a novel intervention was truly effective.
This area also raises interesting questions of justice, social impacts, and access, and these received limited discussion in the Forum. Should special attention be paid to the possible impact of new innovations, especially if that adds to the cost of treatment? Will they indirectly result in the disenfranchisement of certain groups, i.e., the uninsured and the underinsured? Could there be adverse impacts from innovations (e.g., in neuropsychiatry) that might invite improper uses that would unfairly disadvantage individuals?
These larger questions, and others, were discussed at the end of the Forum in order to explore future areas that might benefit from more focused follow-up meetings. Several areas were mentioned as possibilities for the future. First, "translational research" — that is, research that brings basic science from the bench to the bedside — is an important activity in many academic medical centers. Participants felt that more consideration should be given to how incentives for doing such work might be improved. Ethical and policy considerations may act either to facilitate or to inhibit the transfer of basic science findings to the clinic. The Recombinant DNA Advisory Committee at the National Institutes of Health has an important role in this transfer, but has tended too be dominated by basic science considerations rather than the needs of the clinical community. In certain states — for example, New Jersey — agencies have been formed to intervene constructively in the transfer process, identifying obstacles and improving communication.
It may be that new national institutions may be required to explore issues of this kind. In the United Kingdom, the Nuffield Council has served as a non-government, independent forum for discussing a variety of ethical and policy issues. The Lasker Trust, a powerful "name" in science, might be able to guarantee serious attention to such an agency. Under its aegis, projects of a more specialized kind could be pursued. For example, an increasing number of problems surround information, communication, and their impacts on the conduct of research. An example is the well-known "file-drawer" problem in statistics, which results from the fact that negative results are seldom published and meta-analyses therefore depend upon biased samples. Researchers also face increasing database needs, and confront problems of inter-operability among databases; standardization of the ways in which information is handled, stored, and made available. A particularly troublesome contest has arisen between the need for information to serve important public health needs and the requirements for privacy protection. A project of this kind would require persons knowledgeable about computing technology, bioinformatics, and database management — as well as the process of scientific publication. The focus would be on how this information and its management impacts the quality of care. The relationship between the basic biomedical sciences and the improvement of clinical practice is a vital one; yet, as indicated above, the transfer of technology from bench to bedside is often slower than would be desirable. Some of the difficulty may lie within the basic biomedical system itself. A study on the status of the profession in biomedical sciences, including its cultural values and norms in conducting the "stewardship of the profession," could help to identify barriers to transfer. It would examine the way in which the "prestige economy" works in biomedical research, how the rewards structure (promotion and appointment) work, and how these act to influence ethics, values, and behavior. It would consider the support and conduct of research, authorship customs and publication policies, peer review and the behavior of referees, disagreements over credit, and other aspects of the values of the profession. On the clinical side, a parallel analysis could explore and compare the differences in professional tradition, training, publication practices, and the like. Useful comparisons could also be drawn with other national systems of regulation, credentialing, licensing, and insurance.
APPENDIX A.
INFORMAL EXPERIMENTS: THE ETHICAL ISSUES*
Harold T. Shapiro
Professor of Economics and Public Policy
Princeton University
Keynote Address, Lasker Forum on Ethical Issues in Biomedical Research. American Association for the Advancement of Science. Washington D.C. May 15, 2003.
I would like to begin by extending my own word of welcome to all of you to what I hope and believe will be an interesting, instructive and perhaps provocative few days. I also want to express my appreciation to the Lasker Trust, which has a distinguished record in its support of biomedical science, for their enthusiasm and support for this Forum. Most of all, however, I want to thank Don Kennedy, whose own enthusiasm and dedication is primarily responsible for bringing us together to discuss what I believe is a fascinating and potentially important set of issues.
The intent of my remarks is not to set out my own views on the matters we will be discussing. Although I certainly have views on the subject, my expectation is that they may be substantially altered by our discussions, and I see no reason for my views to be given any special priority by having them take up all the verbal space in this opening session. Indeed to the best of my ability, I hope to put my own views in some kind of transitory suspended state so that I can critically re-examine them in the light of our deliberations. The intent of these opening remarks, therefore, is to try to sketch out, in very broad terms, some of the longer term perspectives within which the particular focus of our discussions will fall.
As we think about the ethical issues that might arise when deploying unproven therapies in a clinical setting, what I will refer to as informal experimentation, we are submerging ourselves in a very long stream of human history and concern. As you all know, the relationship between healer and patient has been the focus of moral and/or cultural concern throughout the records of such ancient civilizations as Mesopotamia, China, Egypt and Greece. What is less well known is that in all the ancient civilizations of which we have some record, it was not only the healer-patient relationship, but attitudes toward informal medical experimentation or innovation in a clinical setting that was understood as generating social, cultural and ethical issues. Indeed in these pre-modern societies, all medical experimentation was both informal and necessarily in a clinical setting. In any case, the issues we will be discussing in the next two days or so deposit us in a very ancient, but continuing stream of human history. In modern times these matters fall somewhere in the space between clinical practice and research protocols using human subjects.
Indeed the relative impact of tradition and innovation on medical therapies in the pre-modern world is an interesting aspect not only of the history of medicine and medical ethics, but of evolving cultural attitudes toward the development of human knowledge. Most of you are probably familiar with the existence of the famous Hammurabi Code of Laws which emerged as a cultural product of ancient Mesopotamia. Fewer of you, however, probably recall that the Code deals with issues of informal medical experimentation or medical innovation and medical malpractice, which was normally thought of as the same thing! In particular, there were very heavy penalties for innovations that did not work, especially if they were tried out on patients with high social status. The same was true in ancient Egypt where doctors were strongly discouraged from trying new therapies, and the medical handbooks of the era, even in the much later Hellenized versions, extolled the wisdom of the ancients as the basis for a sound medical practice. Indeed if a patient died after the application of a new therapy, the doctor might very well be executed for malpractice, while if the patient died using traditional therapies, no penalty was imposed! Even the Chou dynasty of China [ca. 200 BC] had set out penalties for medical malpractice, which in ancient China and in the pre-scientific world in general was often equated with medical innovation. Of course as many of you know, ancient Chinese medicine focused on preventive strategies rather than therapeutic modalities. Indeed the ancient Chinese thought of surgery as undignified and doctors — perhaps wisely, given how little was known at the time — were inclined to look for more metaphysical approaches to disease and health.
Interestingly, however, in ancient Greece, the cradle of our civilization, there was a more balanced approach to tradition and innovation. Indeed many believe that the productive interplay between tradition and innovation in ancient Greece is one of the cultural attitudes that makes western civilization so distinct. Indeed in Plato's ideal state, which from our perspective leaves much to be desired, the physician was to be completely free to follow their professional judgment. As you might expect, the Greco-Roman world also accorded a much higher social position to doctors than other ancient civilizations. In that world, doctors were members of a free profession and often negotiated their dealings with their patients through formal contracts.
In summary, in the ancient world new therapies were often introduced only in extremis, and/or practiced on those whose moral status no longer mattered. Indeed this practice or set of attitudes has remained a part of medical practice well into modern times and down to the present day. In my judgment, one of the under-explored areas of bioethics is the moral standing of those near death and what physiological, cultural and ethical meaning can be given to the phrase "near death."
For the most part, however, the scientific, political, economic and cultural forces of the Enlightenment dramatically changed our attitudes toward experimentation and innovation. In the last two or three centuries, innovations of all kinds — scientific, cultural, economic, political, etc. — have become central to how we understand ourselves, how we live our lives and the prospects we see before us. Indeed experimentation and innovation are now seen as perhaps the most valuable and creative of human activities. Perhaps this is why I have often wished I were a scientist in order to more directly participate in one of the most creative human activities ever, and an activity with great moral resonance.
However, for reasons I will articulate in a moment, the extraordinary burst in innovative activity of all sorts that resulted from the forces released by the cultural attitudes of the Enlightenment inevitably raised new ethical issues, and in the field of biomedicine, or biomedical science, these new ethical issues now seem to have become, in part, the domain of bioethics.
Since I am quite aware of both the imperialistic tendencies of bioethics as a field [i.e., its ever-expanding notions regarding the scope of human activity that seems legitimately to come within its purview] and the rising impatience of many investigators and practitioners with the constraints that bio-ethicists tend to introduce, I want to say a word about the subject matter of this meeting and the undeniable fact that ethical behavior always involves what will appear to some as bothersome constraints on our freedom of action.
Our conference will deal with the ethical issues that might arise in the context of deploying unproven medical technologies/practices/drugs and other clinical modalities within a clinical practice environment. As such, it is a distinctively different environment from that of research protocols using human subjects. To be sure, there are some similarities. For example, both may use human subjects for purposes beyond the welfare of the subjects themselves. There are, however, important differences. For example, the various interests being pursued may give rise to fewer conflicts of interest. At the same time, however, these informal experiments currently lack any third party oversight. Perhaps one of the key objectives of our discussions is to increase our understanding of whether or not the ethical obligations that ought to exist between doctors and/or investigators on the one hand and patients/human subjects on the other is substantively different when deploying unproven therapies in a research environment as compared to a purely clinical setting.
In particular, we want to understand better the ethical principles that should govern the introduction of unproven medical products and/or services within a clinical practice environment. Moreover, we would like to understand who, if anyone, should oversee the fulfillment of these obligations.
I think the discussions we are about to engage in are clearly an exercise in applied moral philosophy. The problem is that for most people outside this room, thinking carefully about our ethical obligations is not an everyday activity. We simply trust our instincts and/or our habits of mind. Nevertheless, our everyday activities are full of ethical resonance since virtually all our actions impact the interests of others. From time to time, therefore, it is important to pause and consider whether our habits of mind should be adjusted in some way. The particular matters we will discuss which involve the deployment, one way or another, of unproven therapies in a clinical practice setting not only involve very direct interactions with other persons, but by their very nature involve the consideration of the mutual ethical obligations between doctor and patient under circumstances which may be characterized as containing not only various conflicts of interests, but competing ethical obligations.
Whether we want to refer to the ethical issues that necessarily arise in such circumstances as bioethical issues or simply as ethical issues that need to be addressed is not important. What is important is to recognize that these situations involve well-intentioned parties that necessarily have their own sets of legitimate interests which may not be completely coincident with each other. As a result, conflicts of interest inevitably arise, and while these cannot be avoided, they can be acknowledged, managed, and possibly even regulated. In this latter respect it is important to remember, however, that not all ethical issues are public policy issues, and therefore not all bioethical issues are resolved best by regulations and/or legislation.
To put the matter in somewhat different terms, one of the underlying questions we must address is in what way those deploying unproven therapies in a clinical practice environment need to take the interests of their patients into account when they act, and to assess what restrictions physicians ought to place on their our own freedom of action in pursuit of their legitimate and entirely praiseworthy objectives. These are both very practical matters, and equally importantly, are matters of determining what constitutes, in these circumstances, ethical behavior.
My own entry into the field of bioethics is relatively recent and to me quite unexpected. Indeed when I received a call from the White House to inquire whether I would be willing to chair NBAC, my first reaction was that there must have been some bureaucratic error! Unfortunately, what the White House could not have known is that I seem to suffer from a very peculiar, not well understood and possibly widespread neurological disorder that has one troubling symptom: namely that if someone asks me to do something I take it as conclusive evidence that I have the talent to do the task! As a result, not only did I accept the assignment, but I now teach classes dealing with matters that fall within the intersection of bioethics and public policy at both the undergraduate and graduate levels. At the time I told myself that the reason for my appointment was that I had no announced public position on any of the most controversial issues in bioethics. Perhaps, therefore, the only real qualification I had was that I had not spoken publicly about issues that I had not thought deeply about.
My education in bioethics, therefore, began late, but prospered mightily due to the intellectual and personal generosity and patience of other members of NBAC, some of whom — like Jim Childress, Bernard Lo, Tom Murray, and Alta Charo — are here with us today and are some of the real pioneers in this arena. I am glad to have the opportunity to thank them publicly.
Before I address more fully my perspectives on the over-arching or cross-cutting themes of this conference, I think it may be useful to remind us all of certain aspects of the contemporary environment within which our discussions will be taking place. In this respect, I will focus only on those characteristics of the contemporary environment that might well color the tone or the atmosphere, the "ether" so to speak, of any discussions surrounding ethical issues.
First and perhaps most obviously and importantly, it is critical to recognize that we are living and will continue to live in a society characterized by rather stormy moral weather. In short, we must expect an era where a large variety of new ethical challenges will be constantly before us. There are a number of reasons for this, but I will highlight only four.
To begin with, we are living in an era of change — indeed a period of very rapid change — and change itself always is accompanied by a certain amount of moral anxiety as we try to work out the reallocation of resources, prestige, and status that always accompanies change. In short, the kaleidoscope of changes that now color almost all aspects of our lives means that the rules that we use to live together [our obligations to others] are in constant need of some revision. While modern liberal democratic societies are based on the assumption that change will be pervasive and we can acknowledge that these societies have a truly admirable record at continually working out a revised set of rules, this "working out" always involves considerable moral anxiety, since it inevitably involves winners and losers not only as society's stock of wealth, income, status, etc., gets reallocated, but because our notions of human responsibility and opportunity change.
Thus whether anxiety gives rise to change or change gives rise to anxiety, anxiety and change will be constant companions on our life's journey, and in the era that lies before us, we can expect both rapid change and high levels of moral anxiety.
Second, the current era of globalization will dramatically alter the nature of our ethical obligations to those who reside far from us in both a cultural and geographic sense. In an earlier era, it was much easier to say that our ethical obligations either stopped at our borders, or that our ethical obligations to our nation or to those that share our geography and culture always trumped those to humanity as a whole. In the era before us, this is a more difficult proposition to support. Moreover, since the biomedical enterprise is becoming ever a more thoroughly global one, ethical obligations in this arena can also take on an expanded set of concerns. In any case, in the era of HIV and SARS, it is clear that even issues of national health status are dependent on situations abroad. More generally, as people, ideas, capital and products travel over the world's surface in unprecedented volumes, the web of mutual dependence and obligation that ties us to people everywhere gets thicker and thicker.
Let me turn to the third environmental factor which emanates from the very successes of the biomedical arena itself. Since change is especially pervasive in this arena, we can expect for reasons I have already outlined to be faced with wave after wave of new ethical concerns. As a result, the very success of the biomedical enterprise and all the wonderful changes it generates brings with it both great dividends and new ethical challenges. One of the key ethical challenges, for example, is to decide how this new understanding ought to get deployed and who ought to receive the benefits. To put all this in a more coherent ethical framework, however, we must recall that with all new discoveries come at least four major types of ethical challenges.
They are:
- What is ethical use?
- Who decides what is ethical use?
- Who ought to deal with and absorb the cost of the unexpected side effects?
- How should we deal with the impact on the human narrative?
This latter issue, the impact of scientific discoveries on the human narrative, is perhaps the most important source of unease regarding events of the scientific frontier. By human narrative, I mean the revealed and/or constructed stories that societies develop in order to give some transcendental meaning to their efforts. In view of the contingency of all individuals and their mortality, these stories or narratives serve to connect them to future and past generations in a manner that gives some meaning to their efforts and that enables them to make sense of a world that is somewhat beyond their understanding. Historically, the key characteristics of these narratives are first to ascribe something special to the planet Earth and to human beings, and second to "position" human beings as occupying a place between the natural world that they can understand and control and an aspect of the world that is beyond our understanding. Scientific developments that threaten these characteristics require a change in the narrative, and this is not only an emotionally difficult task, but the narratives themselves are, at very least, great feats of the human imagination, and reconfiguring them is an intellectual challenge as well. In the long sweep of things, the discoveries of Copernicus, Darwin and those who have revolutionized contemporary biology and astrophysics have certainly undermined the contents of many traditional human narratives. After all, we now know we share the same genetic code as all other living things, and that the planet Earth is a tiny speck in an ever expanding universe that is slowly going nowhere, but obeying the laws of thermodynamics. With such new knowledge it is more difficult, for example, to maintain narratives that depend on the uniqueness of human beings and the planet Earth. Indeed it has required us to stop speaking about the meaning of life and focus on how to live a meaningful life. This is one of the many fundamental transformations in the human narrative that our changing knowledge base has required.
In any case, the general proposition or observation that new knowledge raises serious ethical and cultural issues is a very old one. Indeed the history of western literature from its very beginnings in classical times to the present reflects these very concerns [e.g., Sophocles' Antigone, the Argo and Prometheus legends, the continuing popularity of the Faust legend, Mary Shelly's Frankenstein, Somerset Maugham's The Island of Dr. Moreau, Capek's RUR, the 20th century horror movies that focus on science falling into evil hands, etc.]. All these authors and many more reflected on the ambiguity of scientific progress in the sense that while our increasing knowledge base increased our potential to control our lives, it brought with it a new and expanded portfolio of ethical responsibilities. Moreover, this literature has always been concerned about whether or not there was any limit to humankind's capacities and responsibilities.
Thus while ethicists might seem like a tiresome lot, always getting in the way of good works, continually making progress both more difficult and less fun, in the end they are simply trying to help us understand how we can make the most rewarding use of our new knowledge and how in that process we accommodate the interests of others. These interests include the interests both of those who experience change as a loss, and of future generations and ethicists can help us understand why such interests should cause us to place any restrictions on our current freedom of action. These are difficult issues, and we cannot expect them to be resolved easily or "once and for all." In this respect, it may be helpful to recall that while the central issue of political philosophy — namely, why and under what circumstances we should obey anyone — certainly remains incompletely resolved, attempts to carefully consider this issue have yielded untold dividends. Thus even if we fail to solve some of the ultimate questions, we can still make remarkable progress in finding more redeeming ways to live together and new habits of the mind which allow all of us to live a more meaningful life.
Finally, the biomedical enterprise is becoming an ever vaster enterprise, where formally a set of somewhat independent actors are now deeply interdependent in a new set of symbiotic relationships that are more tightly than ever tied to the dynamics of private markets. Independent voices are increasingly rare and conflicts of interest are increasingly common.
For all these reasons and many more, ethical issues will continue to be before us with all the moral anxiety that change brings. Our consolation for all this is twofold, namely: (i) change has many positive benefits, and in a liberal society change is associated with increased freedom and the fuller realization of our individual humanity; and (ii) perhaps these concerns are a sign that we are taking ethics more seriously.
We must also recognize, however, that these issues are in some ways much more difficult to resolve in a liberal democracy where we are committed not only to individual autonomy and moral pluralism as almost the supremely important values, but to the notion that almost every aspect of our lives will sooner or later be replaced by a better idea. Thus even though many still look to authority and tradition for comfort in a dangerous and rapidly changing world, liberals, like myself, continue to celebrate change as adding to our freedom and enabling us to more fully realize our humanity. For liberals, therefore, the pain, dislocation and loss inherent in change are happy burdens, but for others it remains troubling, and events on the scientific frontier may make them a little queasy. We should not make the intellectual error of thinking of these people as Luddites. Their reactions have little to do with lack of education and understanding, or any fundamental opposition to scientific progress. Their concerns have everything to do with the challenge of adapting their human narrative, deciding what is ethical use, concern with unexpected side effects, and wondering who gets to decide how and where this new technology gets deployed.
Indeed in the American context these difficulties and concerns often end up being resolved by the courts. I am not a lawyer, much less a constitutional scholar, but I am struck by how often we rely on the courts or on Presidential executive orders to make decisions that are too controversial for the Congress, or in some cases the state legislatures to make. It is therefore never clear which bioethical issues will be left to the courts, which to private decision makers, and which to the Congress.
While liberals have opted for a difficult ethical environment, I hope it is clear to everyone here that this is precisely the environment most conducive to the continuing vitality of the scientific enterprise. It is not an accident or a coincidence that the ideas of the Enlightenment that focused on a continuing reassessment of our beliefs and understandings, and the notions that we might experience a permanent diet of revolution whether of the Marxian or liberal variety, both arose in the 19th century — coincident with the birth of the modern scientific revolution.
I will conclude my remarks with a brief cautionary note about the history of bioethics as I understand it. In the popular imagination the history of bioethics seems to center around particular episodes thought of as "scandals," or at the very least serious ethical lapses. We all recognize the emotional reaction to such names as Tuskegee, the radiation experiments, the Nazi and Japanese experiments, and the material underlying the Beecher and Pappworth reports, to name a few of the better known examples. The important narrative, however, lies elsewhere. It lies in our growing determination to more fully recognize the moral status of each person and in finding ways to advance the scientific frontier while respecting our ethical obligations to all.
Nevertheless, the history of bioethics in this country reveals a clear pattern not only of our inability as individual scientists and investigators to distinguish between the various interests we serve, but of our reluctance to face up to these conflicts. We need therefore, to consider the appropriateness of developing procedures or "habits of the mind" that help even saints to manage the inevitable conflicts they face. In our area of particular focus — namely, informal medical experiments that involve the deployment of unproven therapeutic modalities within a clinical practice setting — such conflicts often exist. Therefore we need to begin a series of serious conversations between those carrying on these informal experiments and others with interests in this matter. By serious conversations, I mean conversations where all sides agree that they may change their mind and, therefore, enter the discussions as I enter these discussions — namely, with a partial and perhaps transitory suspension of their initial beliefs. In my judgment, such an approach is necessary in order to maximize the chance of finding common ground with respect to the habits of mind that should inform those working in this area and those whose interests are involved in other ways.
Most importantly, we have to face the fact that the key actors here are all doctors and that medical education does a notoriously poor job in training future physicians on how to evaluate, design, and carry out either formal or informal experiments. Finding the appropriate remedy to this deficiency in contemporary medical education might go a long way to helping us all develop those habits of mind that are fully cognizant of the ethical responsibilities experimenters have in this area. These procedures or habits of the mind may or may not help us prevent the work of sinners, but they are meant primarily to help the saints among us to continue our good work while respecting the moral status of persons, and in particular, to behave with the understanding that to employ or use human beings for any purpose beyond their own welfare is a privilege.
APPENDIX B.
Lasker Forum on Ethical Challenges in Biomedical Research and Practice
List of Participants
1. Dr. Grover C. Bagby, Oregon Health & Sciences University
2. Dr. Patricia Baird, University of British Columbia
3. Mr. Robert Bazell, NBC News
4. Dr. Paul Berg, Stanford University Medical Center
5. Dr. Elizabeth Blackburn, University of California, San Francisco
6. Ms. Susan Brink, U.S. News & World Report
7. Mr. W. Michael Brown, Lasker Foundation
8. Dr. John H. Campbell, University of California, Los Angeles
9. Dr. Christine Cassel, Oregon Health & Science University
10. Dr. Lynn Cates, Veterans Administration
11. Dr. Alta Charo, University of Wisconsin Law and Medical Schools
12. Dr. James F. Childress, Center for Biomedical Ethics
13. Dr. Bette-Jane Crigger, Veterans Health Administration
14. Ms. Barbara J. Culliton, TIGR Center for the Advancement of Genomics
15. Dr. Rebecca Susan Dresser, Washington University School of Law
16. Dr. Margaret L. Eaton, Stanford University
17. Dr. Ruth Faden, Johns Hopkins University
18. Rabbi David Feldman, The Jewish Center
19. Mr. James W. Fordyce, Lasker Foundation
20. Mr. Stephen Foster, The Overbrook Foundation
21. Dr. Mark Frankel, American Association for the Advancement of Science
22. Susan Grandis Goldstein, Religion & News Weekly
23. Dr. Henry T. Greely, Stanford University
24. Dr. Kathy Hudson, Johns Hopkins University
25. Mr. James E. Hughes, Lasker Foundation
26. Dr. Neen Hunt, Lasker Foundation
27. Mr. Peter Barton Hutt, Covington & Burling
28. Dr. Judy Illes, Stanford University
29. Dr. Jeffrey Kahn, University of Minnesota
30. Dr. Nancy Kass, Johns Hopkins School of Public Health
31. Dr. Donald Kennedy, Stanford University
32. Dr. Patricia A. King, Georgetown University Law Center
33. Dr. Michael Klag, Johns Hopkins University School of Medicine
34. Ms. Lori P. Knowles, The Hastings Center
35. Dr. Greg Koski, Harvard Medical School
36. Mr. Martin Krasney
37. Dr. Jennifer Kulynych, Ropes and Gray
38. Dr. David Lepay, U.S. Food and Drug Administration
39. Dr. Bernard Lo, University of California, San Francisco
40. Dr. Peter Lurie, Public Citizen's Health Research Group
41. Dr. David Magnus, University of Pennsylvania
42. Dr. Anna Mastroianni, University of Washington School of Law
43. Dr. Richard Merrill, University of Virginia Law School
44. Dr. Jon F. Merz, University of Pennsylvania
45. Dr. Jonathan D. Moreno, University of Virginia
46. Dr. Thomas H. Murray, The Hastings Center
47. Dr. Craig Nichols, Oregon Health & Sciences University
48. Dr. Philip Noguchi, U.S. Food and Drug Administration
49. The Honorable John T. Noonan, U.S. Court of Appeals, Ninth Circuit
50. Dr. Sherwin B. Nuland
51. Dr. Pilar N. Ossorio, The University of Wisconsin Law School
52. Dr. Patrick Reilly, Association of Clinical Research Professionals
53. Dr. John A. Robertson, The University of Texas School of Law
54. Dr. Karen J. Rothenberg, University of Maryland School of Law
55. Dr. William M. Sage, Columbia Law School
56. Dr. Richard Schilsky, The University of Chicago Hospitals & Health System
57. Ms. Noel Schwerin, Backbone Media
58. Dr. Harold T. Shapiro, Princeton University
59. Dr. Lee M. Silver, Princeton University
60. Dr. Gregory B. Stock, University of California, Los Angeles
61. Mr. William C. Stubing, The Greenwall Foundation
62. Dr. Jeremy Sugarman, Duke University
63. Mrs. Leslie Tucker, The Pew Charitable Trusts
64. Dr. LeRoy Walters, Georgetown University
65. Dr. Simon Whitney, Baylor College of Medicine
66. Dr. Keith Yamamoto, University of California, San Francisco
67. Dr. Paul Yock, Stanford University
APPENDIX C.
About the Mary Woodard Lasker Charitable Trust
The Mary Woodard Lasker Charitable Trust was established in 1994 to ensure a universal commitment to the medical research enterprise so that science can wage a successful battle against premature death and physical disabilities from life-threatening disease.
The Trust carries on the legacy of its founder, Mary Lasker, a citizen-champion of medical research, through programs, educational forums, and media outreach efforts that raise awareness about the opportunities and challenges of medical research. The Trust enables superior leadership to secure the future of medical science through public policy initiatives, and it supports scholarly research that informs the funding debate, especially on issues that illuminate both the health and economic payoffs from research.
The Trust sustains a deep commitment to the Albert and Mary Lasker Foundation and its centerpiece effort, the Medical Research Awards Program. Since 1945, the Awards Program has recognized outstanding achievements in basic research, clinical research and public service on behalf of medical science. The Awards serve not only to mark milestones against disease and illness; they also create a venue for bringing the importance of medical science to the attention of the nation's leaders and the general public. The Foundation rests on the belief that scientific investigation, and knowledge of basic human biology and disease processes, are the most reliable, efficient means by which to achieve prolongation of life and reduction in human suffering. Many biomedical advances that we now take for granted were originally the work of Lasker Awardees, advances ranging from deciphering the genetic code to understanding the mechanisms of immunity, from developing the heart-lung machine to creating the polio vaccine.
As biomedical science enters a new era of advancement and challenge, the Trust embraces the goal of refitting Mary Lasker's mission, as a champion of medical science, to urgent national and global priorities that are shaping science policy, funding and research directions. With stunning advances in molecular biology and medical technologies, the sequencing of the human genome, and new therapies emerging from stem cell research and cloning, the rapid progress of science has generated new ethical questions, legal issues, and challenges to public policy. Therefore, the most recent initiative of the Trust, the Ethics Forum project, aims to increase professional as well as public understanding of these daunting concerns and to guide the responses of national leaders to them. The Forum presupposes that support for basic and clinical research may be threatened by deep philosophical divisions in our society about the research enterprise; and that positive steps must be taken toward defining common ground as practitioners, policymakers and the public are confronted with the personal and social consequences of advances in research. The Trust promotes the Forum as an opportunity for professionals with diverse views to participate in respectful debate about the human values that should be considered as research moves forward, about the responsibility of scientists to the public, and about the benefits of research as measured against the concerns that it may raise.
[1] Gawande A. Desperate measures; Francis Moore remade modern surgery. But he couldn't live with the consequences. New Yorker, May 5, 2003, p. 70.
[2] Groopman J. The Reeve effect. New Yorker. November 10, 2003.
[3] Inquiries about the complete set of case studies should be directed to Neen Hunt at the Albert and Mary Lasker Foundation, at 212-286-0222.