Staff Working Paper

BIOTECHNOLOGY AND PUBLIC POLICY:
BIOTECHNOLOGIES TOUCHING THE BEGINNINGS OF HUMAN LIFE

DRAFT RECOMMENDATIONS (REVISED)

Preface

Over the past two years, the Council has devoted much time and energy to examining the current governance of the uses of biotechnologies that touch the beginnings of human life, practices arising at the intersection of assisted reproduction, genetic screening, and human embryo research. The Council has heard from various experts and stakeholders, engaged in its own comprehensive diagnosis of current regulatory mechanisms and institutions, outlined the key findings emerging from that diagnosis, and surveyed various general and specific policy options. The Council now understands a great deal about the current regulatory landscape and has identified concerns that suggest the need for improved monitoring, oversight, and, perhaps, new forms of governmental regulation. Yet we are very far from being able to offer clear and well considered recommendations regarding major institutional reforms. We do not know the precise costs and benefits of overhauling existing regulatory institutions and practices or of creating new regulatory authorities. We do not even know enough about the incidence and severity of some of the possible risks and harms we have identified as causes of concern to judge whether they are serious enough to justify changing the present arrangements. We do not accurately know, for example, how the technologies and practices at the heart of our inquiry affect the health of those whose lives are touched by them-most notably, the children conceived with their aid. Similarly, we do not know how widely preimplantation genetic diagnosis or preconception (and preimplantation) sex selection will be practiced, and for which purposes. Without the answers to such questions, it would be premature at best to recommend dramatic legal or institutional changes. Further research and inquiry, and additional consultations with all the relevant actors, are clearly needed.

Yet even as such inquiry and consultation proceeds, the Council believes that some improvements can and should now be implemented to address some of the concerns identified as a result of our present inquiry. There are a number of measures, described in Sections I and II below, that the Council believes the federal government and the various relevant professional societies should adopt immediately. Most of these suggestions are aimed precisely at addressing the remaining empirical questions described above. These include a call for comprehensive information gathering, data collection, monitoring, and reporting of the uses and effects of these technologies. They also address the need for consumer protection, improving informed decision-making, and enforcement of existing guidelines for practitioners of assisted reproductive technologies (ART). In addition, in Section III, we identify several matters touching the dignity of human procreation that may warrant interim prudent legislative action, especially in light of rapidly arriving innovations that signal new departures in human reproduction. Familiar disquiet regarding human cloning or commerce in human embryos and gametes is augmented by recent reports of, for example, fusion of male and female embryos into one chimerical organism and of the derivation of gametes (in animals) from embryonic stem cells (in principle enabling embryos to become biological parents). Accordingly, while policymakers monitor and gather information and while deliberation continues about the need for better and more permanent monitoring and oversight arrangements, it may be necessary and desirable to enact interim prophylactic limitations. Such limitations would prevent individuals, acting on their own, from introducing major innovations into human procreation in the absence of full public discussion and deliberation about their ethical and social implications and consequences.

The recommendations we offer here are recommendations of the Council as a whole. Though we differ about certain fundamental ethical questions in this field, and especially about the moral standing of human embryos, we have nevertheless been able to agree on several policy suggestions that we believe should command not only the respect but also the assent of most people of common sense, good will, and a public-spirited concern for human freedom and dignity. We have sought to frame these recommendations with sufficient specificity that they might be adopted by the relevant target audiences.       

I. Federal Studies, Data Collection, Reporting, and Monitoring Regarding the Uses and Effects of These Technologies

A. Undertake a federally funded longitudinal study on the health and development impacts of ARTs on children born with their aid. A most important unanswered question before the Council concerns the precise effects of ART and adjunct technologies on the health and normal development of children born with their aid. There have been a few studies, mostly undertaken abroad, reaching variable and sometimes contrary results. An effort has been undertaken, by the Genetics and Public Policy Center in collaboration with the American Academy of Pediatrics and the American Society for Reproductive Medicine, to review all of the existing literature on this question. This is a laudable start, capable of identifying harmful health and development outcomes that should be monitored in the future. The Council strongly believes that what is needed now is a prospective longitudinal study-national, comprehensive, and federally funded-that looks at both the short-term and long-term effects of these technologies and practices on the health of children produced with their assistance, including any cognitive, developmental, or physical impairments. Participation in such a study would, of course, be voluntary.

A seemingly ideal vehicle for this study is the National Children's Study (NCS) now being planned by a consortium of federal agencies led by the National Institute of Child Health and Human Development (NICHD). This study, which is scheduled to begin in 2005, will track the health and development of 100,000 children across the United States from before birth until age 21. Given its great demographic, temporal, and substantive scope, the NCS is uniquely suited to study the health of children conceived with the aid of ART. It is national in scope. It does not require the special recruitment of a population of children conceived with the aid of ART, and all participation is voluntary.  Correcting a major defect in other studies of the impact of ART, the NCS has a built-in control sample, namely, children conceived without the aid of ART.  It will allow researchers to observe and consider health impacts that reveal themselves only years after birth. It will analyze an exceptionally wide range of biological, physical, social, cultural, and other factors that may significantly influence a child's health and development. The NCS has enormous resources at its disposal, as it is being undertaken by a partnership of federal, state, and local agencies, universities, academic and professional societies, medical centers, communities, industries, companies, and other private groups. Finally, the NCS will release its results as the study progresses; thus, one need not wait until 2025 to review the information gathered. The study will publicize results as the children reach certain developmental milestones. In short, the NCS offers an unprecedented and perhaps unrepeatable opportunity to answer questions relating to the well-being of children conceived with the aid of ART.

B. Undertake federally funded studies on the impacts of ARTs on women. Another area where better information would be helpful regards the health and well-being of women who use ARTs. One or more studies, either in conjunction with or separate from the above-mentioned longitudinal study, should be conducted to discover the effects, if any, of the use of ARTs on women's health, including any short-term or long-term hormonal, physical, or psychological impairments. Participation in such a study would, of course, be voluntary.

C. Undertake federally funded comprehensive studies on the uses and effects of reproductive genetic technologies. As noted above, assisted reproduction and genomic knowledge are increasingly converging. Practices such as preimplantation genetic diagnosis and gamete sorting represent the first fusion of these disciplines. Before these practices become routine, it is necessary for policymakers and the public to understand their present and projected uses and effects. To this end, there should be a federally funded comprehensive study, ideally undertaken with the full participation of ART practitioners and their professional associations, on how and to what extent such practices are currently and may soon be employed, and their health effects on children born with their aid. Mechanisms need to be developed for ongoing monitoring of the outcomes of these practices and others to which they may lead. Participation in such a study would, of course, be voluntary.

D. Strengthen and augment the Fertility Clinic Success Rate and Certification Act. As currently written, the FCSRCA is aimed at providing consumers with key information about the pregnancy and live-birth success rates of assisted reproduction clinics in the United States. We believe that the Act should be augmented and strengthened, both to improve this original function of consumer protection and to enable the federal government (through the already existing ART surveillance program at the Centers for Disease Control) to gather information and to monitor the development, uses, and effects of all technologies and practices that touch the beginnings of human life. Toward these ends, the Act and the regulations propounded pursuant to it should be improved and strengthened in the following ways.

1. Enhance Reporting Requirements.

(a) Efficacy: Provide more user-friendly reporting of data, including adding "patients" as an additional unit of measure. Currently, data are reported only in terms of "cycles" of treatment (beginning when a woman starts ovarian stimulation or monitoring), rather than in terms of individual patients treated. Thus, it is impossible to know how many individuals undergo assisted reproduction procedures in a given year, how many patients achieve success in the first (or second or third) cycle, how many women fail to conceive, and the like. Presenting results in terms of "numbers of individuals" (in addition to "numbers of cycles") would be very helpful to prospective patients and would yield more precise information for policymakers.ⁱ  Also, this information should be presented with any qualifying language or additional information that would help to avoid confusion for prospective patients or the public.ⁱⁱ

(b) Risks and Side Effects: Require the publication of all reported adverse health effects. Adequate consumer protection requires informing prospective users and buyers of the known hazards connected with what they are using and buying. Yet there is today no mechanism for the publication of information regarding adverse health effects of assisted reproductive technologies, either on the adult patients or on their children. At the present time, the CDC does collect data on complications and adverse pregnancy outcomes, including low birth weight and birth defects for each live born and stillborn infant, but this information is not made public. Knowledge of such adverse effects is of paramount concern for prospective patients, policymakers, and the public at large. The CDC should publish its data on the incidence of adverse effects on women undergoing treatment, as well as on the health and development of children born using ART. In order not to confuse or unduly alarm prospective patients or the public, the CDC should include in its publication comparative data on the incidence of such effects for unassisted births, as well as any other relevant information that could help prevent misimpressions regarding the nature and magnitude of the hazards associated with ART.

(c) Costs to the patients: Require the reporting of the average prices of the procedures and successful pregnancy. There is currently no comprehensive source of information regarding the costs borne by the patients seeking treatment involving assisted reproductive technologies. Not surprisingly, prospective patients are keenly interested in this information. Moreover, policymakers interested in questions regarding equality of access and related matters would greatly benefit from such information. It would also shed light on whether incentives currently exist that may induce patients and clinicians to engage in potentially risky behavior, such as the transfer of multiple embryos in each cycle, in an effort to reduce costs. While the publication of such information may cause some confusion, or worse, may induce some practitioners to lower their fees but at the expense of health and safety, the Council believes that the consumer benefits of providing such information outweigh these speculative harms. This is especially true if this information about costs to the patient is published alongside the present and recommended information relevant to patient health and safety.

(d) Innovative Techniques: Include information on novel and experimental procedures. A key area of concern for the Council is the ease and speed with which experimental technologies and procedures (such as intracytoplasmic sperm injection [ICSI] or preimplantation genetic diagnosis [PGD]) move into clinical practice, even in the absence of careful clinical trials regarding the efficacy and long-term effects. It would be useful for consumers and policymakers to understand more fully how each clinic manages the process of introducing new technologies and practices and what safeguards are in place. Such information would include the human subjects protections in place; the extent to which technologies are tested in animals; the standards that must be satisfied before a given procedure is deemed fit for clinical use; and the measures taken to evaluate safety and efficacy.

(e) Adjunct Technologies: Require more specific reporting on the frequency of, and reasons for, uses of specialized techniques such as ICSI, preimplantation genetic diagnosis, sperm sorting for sex selection, etc. Little is understood about the frequency and uses of the various adjunct technologies and practices complementing standard IVF. Under the present system, the CDC already collects and reports information relating to the incidence and uses of some adjunct technologies. The present approach could be greatly improved, however, by modestly changing the relevant law to require information on additional adjunct procedures (particularly those that combine assisted reproduction with human genetic technologies), as well as to require the reporting and publication of somewhat more detailed information relating to the reasons patients elect to use those procedures that are already subject to reporting requirements. For example, the present system of reporting sheds little light on precisely why patients chose ICSI as their preferred method of fertilization. The CDC reported that in 2000, ICSI was used in 46 percent of all IVF cycles, yet in nearly 40 percent of these instances the prospective patients did not suffer from male factor infertility. Also, because results are reported in terms of cycles rather than patients (as discussed above), it is impossible to know how many individuals used ICSI.

Other techniques, particularly those fusing reproductive technology and genomic knowledge, are not reported at all under the present version of the Act. There is no requirement to report the number of cycles using PGD, much less the reasons for using PGD. For example, how many patients using PGD are infertile? How many have family histories of genetic disorders? What sort of genetic screening is being done? For aneuploidy and single-gene mutations? For donor siblings? For non-disease related traits? There is also no reporting of any practices in which sex selection occurs and the reasons for undertaking them. Consumer protection and public policy would be enhanced if this information were available and published. Consumers would benefit from knowing how much experience a given clinic has in performing such procedures. Policymakers and the public would benefit from knowing how, why, and to what extent genomic knowledge is being used to enhance control over procreation.

2. Enhance Patient Protections: Informed Decision-Making.

Provide model decision-making forms. The present Act would be greatly improved by providing for the promulgation of easy-to-read model consent forms that include information on the possible health risks to mother and child, the novelty of the various procedures used, the number of procedures performed to date, the outcomes, and the various safeguards in place to ensure that such procedures are safe and effective.

3. Improve Implementation.

(a) Enforcement: Provide stronger penalties to enhance compliance with the Act's requirements. Under the Act as currently written the only penalty for noncompliance is the publication of the names of non-reporting clinics. This is insufficient, given the importance of clinic compliance to ART consumers and the greater public. The penalties should reflect the magnitude of harms to be avoided. We leave to legislators the question of what precisely these should be.

(b)   Funding: Increase funding for implementation of the Wyden Act. CDC's budget should be augmented sufficiently to enable it to undertake the additional measures suggested above. In this way, the increased oversight called for above will be borne by the government rather than by the individual patient. We leave to legislators the question of how much additional funding would be required.

II. Increased Oversight by Professional Societies and Practitioners

Professional oversight has traditionally been the principal mechanism of regulation for the practice of medicine. While there is a well developed body of professional guidelines and standards for the clinical practice of assisted reproduction, the Council has identified the following substantive areas that require attention and improvement:

A. Improve informed decision-making. Clinicians and their professional societies should make efforts to improve the current system of informed decision-making to conform to the concerns and suggestions described above. ASRM and SART (Society for Assisted Reproductive Technology) should pay attention not only to helping devise improved and standardized consent forms, but also to recommending procedures to their members for discussing it properly with patients and securing their meaningful consent. For this purpose, they should consider making training sessions on this subject a requirement of membership.                

B. Treat the child conceived through ART as a relevant patient. ART clinicians should take measures to ensure the health and safety of all participants in the ART process, including the children who are born as a result. To this end, ART clinicians should collaborate with pediatricians in making decisions that might affect the health and safety of these children. Moreover, they should not view their responsibility as ending once a pregnancy has been initiated. Clinicians and professional societies should also cooperate fully and vigorously with any efforts (such as the studies described in part I above) to study the effects of ART and related practices on the health and development of such children. In addition, the Council strongly endorses a very specific substantive recommendation: clinicians and professional societies should take additional concrete steps to reduce the incidence of multiple embryo transfers and resulting multiple births.

C. Improve enforcement of existing guidelines. There are today a host of reasonable guidelines in place for clinicians and practitioners engaged in ART. However, the relevant professional societies need to take stronger steps to ensure that these guidelines are followed. For example, one such professional society "actively discourages" the use of PGD for sex selection for non-medical purposes, yet several prominent members of the society openly advertise the practice. Professional societies must clarify the contours of appropriate conduct and adopt reasonable mechanisms of enforcement.

D. Improve procedures for movement of experimental procedures into clinical practice. Professional societies and clinicians should develop a more systematic mechanism for reviewing experimental procedures before they become part of standard clinical practice. Such a system might include requirements for animal studies, IRB oversight, and formal discussion and ongoing (and prospective) monitoring of the significance and results of novel procedures.

E. Create and enforce minimum, uniform standards for human subjects protection. At present there is no systematic, mandatory mechanism for protecting human subjects who are engaged in experimental ART protocols not affiliated with institutions receiving federal funds. This problem is compounded by the fact that there is not a clear distinction between research and innovative clinical practice in the context of ART. Investigational interventions that could affect the health and well-being of children conceived using ART should be subjected to at least as much ethical scrutiny and regulatory oversight as investigational interventions affecting other human subjects of research.  Furthermore, it could be argued that a higher degree of scrutiny is justified in this context because the research affects a vulnerable population.  Current research policies establish special protections for children and fetuses in research.  For similar reasons, there is a need for special protections when research involves interventions in embryos that could later affect the health and welfare of the resulting live born children.  Clinicians and their professional societies should adopt measures (such as IRB-like oversight) to provide safeguards to protect the health and well-being of all human subjects.

F. Develop self-imposed ethical boundaries. Clinicians and professional societies would be well advised to establish for themselves clear boundaries defining what is and what is not ethically appropriate conduct, regarding both research and clinical practice. Without such guidance rogue clinicians and scientists may engage in practices that will, fairly or unfairly, bring opprobrium on the discipline as a whole. Practices such as the fusion of male and female embryos, use of gametes harvested from fetuses (or produced from stem cells) to create embryos, and transfer of embryos to non-human uteri for purposes of research fall squarely into this category. The relevant professional societies should preemptively take a firm stand against such practices and back it up with meaningful enforcement.

III. Targeted Legislative Measures to Defend the Dignity of Human Procreation

In the course of our review, discussion, and findings, we have encountered and highlighted several particular practices and techniques (some present, some likely forthcoming) touching the beginnings of human life that raise new and distinctive challenges to the special character and dignity of human procreation. Given the importance of the matter, we believe these require special attention, not only from professional societies but also from the people's representatives. Especially because technological innovations are coming quickly and because there are today no other public institutions charged with setting appropriate limits, we believe the Congress should consider some limited targeted measures that might give expression to and provide protection for the dignity of human procreation, by restricting or limiting (at least for the time being) the practice of a number of carefully defined activities. These measures would remain operative at least until policy makers and the public can discuss the possible impact and human significance of these new possibilities and deliberate about how they should be governed or regulated.

The benefits of such Congressional legislation, as we see it, are multiple:

(a) It could affirm and teach about some of the goods that we hold dear (respect for the humanity of human procreation, respect for women who use ARTs and children conceived with their aid, respect for nascent human life).

(b) It would institute a temporary moratorium on certain practices, setting a few carefully defined boundaries on what may be done and preventing any individual from acts that would radically alter what is acceptable in human procreation without prior public discussion and debate.

(c) If carefully drafted, it would not interfere with important scientific research. On the contrary, it could serve to protect the reputation of honorable scientists and practitioners of assisted reproduction against the mischief of "rogues," whose misconduct might invite harsh and crippling legislative responses.

(d) Practically, it would place the burden of persuasion on those innovators who would transgress these important boundaries without adequate prior public discussion or due regard for social or moral norms.

(e) It would demonstrate a way forward for public governance in these areas, and would demonstrate that scientists and humanists, physicians and laymen, liberals and conservatives, "pro-lifers" and "pro-choicers" can find aspects of our common humanity that they are willing to defend collectively and by deliberate agreement.

Legislative concern for the integrity and dignity of human procreation might give rise to a fairly wide range of specific provisions, and the Congress should consider these in their full array. But the concerns we have taken up in this report, and which emerge from our findings, suggest to us a few that are especially crucial, and also especially likely to command fairly broad assent. They may be usefully grouped around four principles or desiderata, each pointing to one or two particular provisions we believe to be in order and that we now recommendⁱⁱⁱ:

1. Respect for the humanity of human procreation, preserving a reasonable boundary between the human and the non-human (or, between the human and the animal) in the beginnings of a human life. The question of the human-animal boundary in general can, in some respects, be quite complex and subtle, and the "mixing" of human and animal tissues and materials is not, in the Council's view, by itself objectionable. In the context of therapy and preventive medicine, we accept the transplantation of animal organs or their parts to replace defective human ones; we welcome the use of vaccines and drugs produced from animals. Looking to the future, we do not see any overriding objection to the insertion of animal-derived genes or cells into a human body-or even into human embryos and fetuses, where the aim would be to prevent a dread disease in the developing child. And in the context of biomedical research, we see little objectionable in inserting human stem cells into animals-though we admit that this is a scientifically and morally complicated matter. But in the context of procreation-of actually mixing human and non-human gametes or blastomeres at the very earliest stages of biological development-we believe that the ethical concerns surrounding that boundary are at their most acute, and at the same time that the prospect of drawing reasonable lines is greatest and most crucial. One bright line should be at the creation of animal-human hybrid embryos, produced ex vivo by fertilization of human egg by animal (e.g., chimpanzee) sperm (or the reverse): we do not wish to have to judge the humanity or moral worth of such an ambiguous hybrid entity (e.g., a "humanzee," the analog of the mule); we do not want a possibly human life to have other than human ancestors. A second bright line would be the insertion of ex vivo human embryos into the bodies of animals: an ex vivo human embryo entering a womb belongs only in a human womb. If these lines should be crossed, it should only be after clear public deliberation and assent, not by the private decision of some adventurous or renegade researchers. We therefore recommend that, in an effort to guard the humanity of human procreation, the Congress should:

• Proscribe the transfer, for any purpose, of any human embryo into the body of any member of a non-human species; and
• Prohibit the production of a hybrid human-animal embryo by fertilization of human egg by animal sperm or of animal egg by human sperm.^iv

2. Respect for women and human pregnancy, preventing certain exploitative and degrading practices. Respect for women with regard to assisted reproduction encompasses many things, including respect for their health, autonomy, and privacy; these are by and large properly attended to in current assisted-reproduction practices. But in the face of some new technological possibilities, we recognize that respect for women also involves respecting their bodily integrity and the dignity of a human pregnancy. A number of animal experiments using assisted reproductive technologies have shown the value of initiating pregnancies purely for the purpose of research on embryonic and fetal development or for the purpose of securing tissues or organs for transplant. We generally do not object to such practices in other animals, but we do not believe they should, under any circumstances, be pursued in humans, or that human pregnancy should be initiated using artificial reproductive technologies for any purpose other than to seek the birth of a child. A woman and her womb should not be regarded or used as a piece of laboratory equipment, as an "incubator" for growing research materials, or as a "field" for growing and harvesting body parts. We therefore recommend that, in an effort to express our society's profound regard for human pregnancy and pregnant women, Congress should:

• Prohibit the transfer of a human embryo (produced ex vivo) to a woman's uterus for any purpose other than to attempt to produce a live-born child.

Respect for children conceived with assisted reproductive technologies, securing for them the same rights and human attachments naturally available to children conceived in vivo. We believe that children conceived with the aid of assisted reproductive technologies deserve to be treated like all other children, and to be afforded the same opportunities, benefits, and human attachments available to children conceived by without the aid of ART. If some care is taken, this can surely be accomplished, as it has been for twenty-five years with in vitro fertilization as ordinarily practiced. But as we have seen, certain applications of embryo manipulation and assisted reproductive techniques could deny to children born with their aid a full and equal share in our common human origins, for instance by denying them the natural connection to two human genetic parents or by giving them a fetal or embryonic progenitor. We believe that such departures and inequities in human origins should not be inflicted on any child. We therefore recommend that, in an effort to secure for children born through assisted reproductive technologies the same rights and human attachments naturally available to children conceived in vivo, Congress should:

• Prohibit attempts to conceive a child^v
  
  • by any means other than the union of egg and sperm;
  • by using gametes obtained from a human fetus or derived from human embryonic stem cells; and
  • by fusing blastomeres from two or more other embryos.     

4. Respect for early stages of nascent human life, setting some agreed upon boundaries on how embryos may be used and treated. What degree of respect is owed to early human embryos will, almost certainly, continue to arouse great controversy. But we all agree that human embryos deserve, as we have said, "(at least) special respect."^vi Accordingly, we believe some measures setting upper limits on the uses of embryos in research and limits on commerce in human embryos may be agreeable to all parties to the ongoing dispute over the moral status of human embryos. Along these lines, we believe that Congress should:

• Prohibit the use, or the preservation, of those embryos that are being used solely for the purposes of research, beyond a designated stage in embryonic development^vii; and
• Prohibit the buying and selling of human embryos.^viii

Moreover, these concerns, combined with a certain ambiguity in the patent laws described in the preceding pages, also suggest to us the need for a provision instructing the United States Patent and Trademark Office not to issue patents on claims directed to or encompassing human embryos or fetuses at any stage of development; and amending Title 35, United States Code, section 271(g) (which extends patent protections to products resulting from a patented process) to exclude these items from patentability. The language of any such statute would in our view need to take some care not to exclude from patentability the processes that result in these items, but only the products themselves.