Joseph Palca

A Word to the Wise

Legislation with sweeping impact often can seem quite obscure and innocuous. Consider this example. Title I, Subtitle A, Part III, Section 121, Paragraph (c) of the National Institutes of Health Revitalization Act of 1993 contains the following sentence: The provisions of section 204(d) of part 46 of title 45 of the Code of Federal Regulations (45 CFR 46.204(d)) shall not have any legal effect. On its face, this sentence would not seem to merit much attention, and in fact, as the bill sailed through Congress this past year, it didnt get much. But little more than a year ago, this sentence would probably have prompted a presidential veto, because for the first time in more than a decade, it allows the federal government to fund research on in vitro fertilization (IVF). What a difference a year makes. The history of 45 CFR 46.204 (d), as it is fondly known to its intimates, tells a fascinating story of science policy problem solving. The expunged section of the Code of Federal Regulations concerns the protection of human subjects. It prohibits funding of IVF research without approval from an Ethics Advisory Board. The requirement was established in the mid-1970s, when the possibility of test-tube babies thrilled the public but troubled ethicists, philosophers, and theologians. By itself, 45 CFR 46.204(d) would not have limited the governments ability to fund research on in vitro fertilization. The Carter administration created the Ethics Advisory Board but then let its charter expire. Before it went out of existence, the board had completed a report on the ethics of IVF and embryo research. The board had determined that IVF was an ethical procedure and that research intended solely to improve the success rate of the process was also ethically acceptable. But the Reagan and Bush administrations failed to renew the boards charter, and without a board, government couldnt fund IVF research, so there was a de facto moratorium. Both the research community and research administrators at the National Institutes of Health chafed under this restriction. For researchers, it meant that private funds had to be used for IVF research. That didnt stop medical centers from offering in vitro fertilization to infertile couples, and over the decade of the 1980s the number of IVF centers around the country grew from a handful to several hundred. There have now been 23,000 babies born by IVF in this country, but the success rate of the procedure is still depressingly low and the cost alarmingly high. For research administrators, its been frustrating not to be able to support a promising medical technology. …

Scientific Misconduct: Ill‐Defined, Redefined

Bureaucracies work most efficiently with matters that are well defined. Fail to compute your alternative minimum tax, and a bureaucracy will spring into action. Commit an act of scientific misconduct, however, and a bureaucracy tends to fibrillate. Scientific misconduct tends to be a lot like pornography: people think they know it when they see it, but it is extremely difficult to define. Bureaucrats have a hard time deciding when misconduct has occurred and then proving it when they are convinced that it has. For example, after nearly a decade of investigations, appeals bodies tossed aside two controversial cases. The cases involved AIDS researcher Robert Gallo, who was accused of misusing a sample of the AIDS virus provided him by another researcher and immunologist Theresa Imanishi-Kari, a colleague of Nobel laureate David Baltimore, who was accused of fabricating data. Justice may have been served by these decisions, but they did not reflect well on the governments ability to deal with misconduct cases. Of course, its unfair to blame the federal bureaucrats alone. Few in the scientific establishment can be accused of doing a good job of dealing with scientific misconduct. But because federal money is involved, Congress has insisted that the government try to do better. To that end, as part of the 1993 National Institutes of Health Revitalization Act, Congress required the Secretary of Health to create a Commission on Research Integrity. That commission, chaired by reproductive biologist Kenneth Ryan at Harvard Medical School, proposed thirty-three improvements (Integrity and Misconduct in Research, Report of die Commission on Research Integrity, U.S. Department of Health and Human Services, Washington, D.C., 1995). Secretary of Health Donna Shalala then asked her science policy advisor, William Raub, to make recommendations on how to implement the commissions recommendations. Raub made his recommendations on 14 June of this year. The most significant - and most controversial - change the commission recommended was in the definition of scientific misconduct. At present, it is based on the three sins of falsification, fabrication, or plagiarism. The Ryan commission concluded that this did not go far enough in defining an unacceptable breach of professional ethics by scientists. For example, a scientist, who knowingly sabotaged anothers work would not be guilty of misconduct under the current definition. In addition, a scientist could leave a collaborators name off a paper despite his or her significant intellectual contribution without being guilty, of plagiarism. …

Animal Organs for Human Patients

Having worked long and hard to come up with a manageable set of procedures for dealing with organ transplants from one human to another, health officials have more work ahead of them. Recent scientific progress threatens to take xenotransplantation--using animal organs for human patients--off the drawing board and into the clinic. That means a new set of social, legal, and ethical guidelines for when such transplants will be allowed. For the immediate future, this shouldnt be an enormous problem. Only a few experimental protocols using xenografts are ready for clinical trials. But it is certain that the number will grow, and federal agencies are already trying to decide how to regulate this new biomedical frontier. The history of xenografts is long and controversial. As long ago as the first decade of this century French scientists experimented with rabbit, pig, and goat kidneys to treat patients with renal insufficiency. Later attempts were made with lambs and nonhuman primates. One patient received a chimpanzee kidney in 1963 and survived for nine months. In 1984 surgeons at Loma Linda University transplanted a baboon heart into sixteen-day-old Baby Fae, and as recently as 1993 researchers at the University of Pittsburgh transplanted livers from baboons into human patients. In every one of these cases, the transplants failed because of immune rejection of the foreign tissue. Still, lately the prospects for success have grown. Research has brought a better understanding of the various types of immune response that lead to organ rejection, and research teams have developed strategies to cope with the problem. New immune modulating drugs have also arrived that increase the odds of success. There have always been moral objections to using animal organs in humans. To some it seems dangerously close to playing God. Others object to using vertebrate animals for selfish human needs. Still others worry that the cost will create inequities in health care. The procedure is certain to be expensive, and there is a realistic concern that only the rich will be able to afford lifesaving animal organs. The Food and Drug & Administration has recently decided that its regulatory authority extends to many proposed xenotransplant protocols, but not for any of these ethical reasons. The FDA decided two years ago that any cells that were manipulated after they were taken out of a living animal and then put back into a human would be subject to agency oversight. The rationale for this, according to Philip Noguchi, director of the FDA Division of Cell and Gene Therapy, was that if the preparation of cells involved a manufacturing process, the FDA is responsible to make sure that the manufacturing does not create safety issues for the recipient. …

Doing Things with Embryos

A federal advisory panel has given its ethical blessing to research on human embryos - at least some kinds of research on human embryos [see also embryo research panel symposium, this issue, pp. 36-461. The panels final report makes it likely, but still not certain, that the National Institutes of Health will begin funding such research, which until now has been off limits for federal support. The de facto moratorium on federal funding for research on human embryos and in vitro fertilization (IVF) came about because of a quirk in the rules for the protection of human subjects of experimental research. The rules said all IVF research had to be approved by the Ethics Advisory Board (EAB), a legislatively mandated body at the Department of Health. But the Bush and Reagan administrations declined to create an EAB, so no research could be approved. The advisory panel, dubbed the Human Embryo Research Panel, was formed last year at the urging of Dwayne Alexander, director of the National Institute of Child Health and Human Development. The NIH Revitalization Act of 1993 removed the requirement for EAB approval, thus breaking the bureaucratic logjam. But Alexander was not anxious to plunge headlong into the tricky ethical currents of embryo research, and asked that a panel be established to guide NIHs funding decisions. From the time the panel members first met in February, they were greeted with a hostile reaction from the religious right. In addition to appearing at meetings, pro-life/anti-abortion activists flooded panel members with mail, castigating embryo research in general and in some cases leveling personal attacks against members of the panel for even considering its ethical acceptability. I was surprised at the personal nature of some of their objections, says panel member Thomas Murray, director of the Center for Biomedical Ethics at Case Western Reserve University. Murray says many critics made ad hominem attacks against panel members, and that many of their criticisms were irrelevant to the panels mission. For example, Murray says some letters he received carried a line drawing of a fetus with a catheter stuck into its brain. In fact, the embryo panels charge was to consider research on the early embryo - prior to the formation of a neural tube, let alone a brain. The panel presented its conclusions at a public meeting on 27 September. The panel placed potential research projects into three categories: acceptable, unacceptable, and possibly acceptable, but needing further consideration. Research aimed at improving the success rate of IVF and research involving defective embryos that would otherwise be discarded following IVF procedures were the kinds of projects the panel deemed acceptable. …

The fifth commission.

The ability to learn from mistakes is one serviceable definition of intelligence. More often than not in Washington, legislators and bureaucrats seem to stare right through past errors in judgment. But there are exceptions, and now the U.S. Congress is showing signs of intelligence when it comes to establishing a national commission on biomedical ethics, There have been four attempts to establish such commissions in the past, and for both good and not so good reasons, none of these commissions is in operation today. In an attempt to learn what worked and what didnt, Senators Mark Hatfield (R-Ore.), Edward Kennedy (D-Mass.), and Dennis DeConcini (D-Ariz.) asked the Office of Technology Assessment to prepare a background paper exploring the strengths and weaknesses of past commissions and presenting options (OTA doesnt make recommendations) for creating a successful new one. The National Research Act of 1974 created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. That commission consisted of eleven members: five scientists, three lawyers, two ethicists, and one person in public affairs. The Secretary of Health, Education and Welfare named the members. The commission met monthly during its four-year existence, and it had a staff of sixteen. Its most lasting impact was the creation of ethical guidelines to protect human subjects who might not be capable of giving informed consent, such as prisoners, children, and the mentally infirm. OTA reportedly concludes that both the National Commission and the Ethics Advisory Board that was its successor at the Department of Health suffered from being a part of the agency they were supposed to be advising. Although the legislation creating the National Commission required that the secretary of health either accept its recommendations within 180 days or publish a Federal Register notice saying why they were being rejected, that didnt always happen. In one case, in proposed regulations involving the institutionalized mentally infirm, that requirement was ignored. A similar problem ended the Ethics Advisory Board. When it was created, the secretary appointed an eleven-member board made up of lawyers, a theologian, a philosopher, clinicians, researchers, and a member of the public. But after two years, the health department simply disbanded the board, despite a law requiring its existence. Although there are lots of possible explanations for why the department took such a step, the most relevant is because it could. …

Keeping Genetic Information Under Wraps

Nothing focuses the mind like a deadline, and while it may not always seem that way in Congress, legislators have a way of slipping deadlines into bills when they really want to get something done. A perfect example of this phenomenon is congressional movement on the subject of privacy. Although it wont happen right away, it now appears likely that lawmakers are ready to take on the issue of protecting the privacy of medical records. The impetus for grappling with this issue comes from several directions. When President Clinton proposed sweeping health care reform legislation, it quickly became clear that if the federal government were to assume a broader role in providing medical insurance, it would have to standardize medical record keeping. A national, computerized database of medical records would speed payments, help prevent fraud, and provide crucial data for making health care policy decisions. For epidemiologists it would be a research boon, providing a volume of health care data unmatched in the world. But a national database raised some troubling questions, too. Who would have access to the information? How would it be protected? Could it be shared among federal agencies? What if the Internal Revenue Service could track you down the minute you went for a flu shot? Civil libertarians, already concerned about government invasions into personal matters, saw such a database as the harbinger of a totalitarian state. Of course, health care reform floundered, and the immediate pressure to grapple with the privacy issue subsided. But another factor was helping to keep medical privacy in the public eye. Advances in human genetics have made it possible for physicians to test people for their susceptibility to diseases. At first it was relatively rare diseases, like Huntington disease and Severe Combined Immune Deficiency. But by the mid-1990s the discovery of a gene called BRCA1 made it possible to test for a susceptibility to breast and ovarian cancer, and last year researchers were close enough to discovering genes for Parkinson disease and prostate cancer to develop genetic tests for those conditions as well. While the tests were potentially useful in making medical judgments about treatment options, many worried that their genetic makeup could be used against them, especially by employers or health insurers who could learn about the likelihood of their future health problems. This prompted several states to adopt legislation specifically protecting the privacy of genetic information as a way of protecting individuals from discrimination based on their genetic makeup. …

A New National Bioethics Commission—Maybe

On 3 October 1995, President Clinton wanted to show how committed he and his administration were to protecting human subjects in research. On that day he accepted a report from the Advisory Committee on Human Radiation Experiments, a national commission that had been looking into allegations that nearly fifty years ago,, at the height of the Cold War, people had unknowingly participated or had been coerced into participating in government-sponsored experiments on the effects of ionizing radiation. Some had, the commission concluded, and the president felt moved to issue a public apology to all those whose rights may have been violated and promised it would never happen again. To back up his promise, the president announced two actions. First, he asked all federal agencies involved in research on human subjects to review current rides for protecting human subjects. Second, he announced his intent to create a National Bioethics Advisory Commission, a fifteen-member body appointed to oversee, among other things, the appropriateness of government-sponsored research. According to the presidents 3 October announcement, NBAC (pronounced En-back) will have a broad mandate to examine the ethical conduct of biomedical research in the U.S. Its first responsibility will be to review the adequacy of each federal agencys rules for the protection of human subjects. Beyond that, NBAC will advise (1) on the appropriateness of departmental, agency, or other governmental programs, policies, assignments, missions, guidelines, and regulations as they relate to bioethical issues arising from research on human biology and behavior and (2) on applications, including the clinical applications, of that research. NBAC is supposed only to identify broad principles, not review specific programs. NBACs first priority will be to look into the management and use of genetic information, as well as questions raised by the patenting of human genes. After it tackles these areas, NBAC can set its own agenda, so long as the topics picked are related to biomedical research and public health, relevant to the federal governments interest in research, and not covered by another bioethics panel--although the latter shouldnt be too big a hurdle since there are virtually no federally chartered bioethics panels around these days. And its to do all this in just two years. NBAC is slated to go out of business two years from the day it formally opens its doors--although that could change if the president decides to keep it around longer. …

New watchdogs in Washington.

The fortunes of federally chartered biomedical ethics advisory bodies are looking up. After nearly a decade when bioethics committees were either kept in suspended animation or allowed to function but given no authority, there are clear signs in Washington that 1993 will see one or more bioethics committees formed with significant power to shape public policy. Two factors are responsible for the sea change. First, in the waning years of the Bush administration there was growing frustration in Congress with White House willingness to give in to demands from the ultra-right wing of the Republican Party. The resentment began early in the Bush years. A pro-life litmus test for the traditionally nonpartisan post of director of the National Institutes of Health (NIH) sent a clear message. The point was driven home for many in Congress when the administration ignored its own advisory committees recommendation and extended a moratorium on funding for fetal tissue transplant research. Several committees in both the House of Representatives and the Senate began drafting legislation that would create ethical oversight committees to protect sensitive research. The idea was to separate true ethical conundrums from political expediency. The second factor promising change is, of course, the electron of Bill Clinton. Within days of the election, career federal bureaucrats whose political sympathies were never in line with the Bush administration began making plans to undo some of the conservative agenda enacted by executive fiat. Within days of his inauguration, Clinton signed orders overturning the moratorium on federal funding for research on transplantation using fetal tissue from induced abortions, reversing the gag order that prohibits doctors in federally funded clinics from discussing abortion as a birth control option, and permitting foreign aid to nongovernmental family planning organizations that offer abortion services. It will take some negotiating between Congress and the new administration to decide how these changes should best be implemented. Last year, both houses of Congress passed the NIH reauthorization bill that would have created a watchdog ethics advisory board in the Department of Health and Human Services. According to the bills language, the secretary of the department would be obliged to convene the ethics board if he or she intended to veto spending for a scientific project that had already been approved for funding by a peer review panel. If the board determined that the research was ethically justified, the secretary would have to release the funds for the project. …