Human Germline Genetic Modification (HGGM) is not yet possible, nonetheless there
has been considerable discussion of the scientific, ethical, and safety
issues that surround it, and a number of recommendations have been made
for specific policy changes. In this section, we present policy options
that respond to the many divergent perspectives regarding HGGM.
For some, the appropriate policy choice is clear and simple: HGGM should be banned. Those holding this view are motivated by either the perceived physical risks or ethical risks posed by the technology, or both. Therefore they support policies to ensure that HGGM is not attempted.
Others believe there may be acceptable uses of HGGM in the future, but want to be sure that appropriate limitations are set, through government or other oversight, to ensure safe and ethical use.
Still others want to encourage innovation in HGGM. From this perspective, regulation, if any, should allow prospective patients and scientists considerable autonomy to move forward in attempting germline modification in humans.
For some, the appropriate policy choice is clear and simple: HGGM should be banned. Those holding this view are motivated by either the perceived physical risks or ethical risks posed by the technology, or both. Therefore they support policies to ensure that HGGM is not attempted.
Others believe there may be acceptable uses of HGGM in the future, but want to be sure that appropriate limitations are set, through government or other oversight, to ensure safe and ethical use.
Still others want to encourage innovation in HGGM. From this perspective, regulation, if any, should allow prospective patients and scientists considerable autonomy to move forward in attempting germline modification in humans.
At the present time, the safety risks of attempting HGGM greatly
outweigh the benefits, leading many to conclude that an outright ban is
warranted. In addition, many alternatives to HGGM, including Preimplantation Genetic Diagnosis (PGD), would
often allow prospective parents to have children free of inherited
genetic disease. Given these alternatives, some proponents of a ban
assume the technology’s primary use would be to create “designer
babies” with enhanced attributes or capabilities, and argue that most
Americans view this application as inappropriate, with the potential to
alter social relationships and society as a whole in a dramatic and
negative manner. Further, advocates of a ban argue that the benefits to
the few couples who might desire to use HGGM to avoid serious genetic
disease need to be weighed against the safety concerns and the risks to
the future of humanity. Based on this calculus, they conclude that the
risks of HGGM are too great to allow it to develop at all.
In the United States, several approaches could be used to ban HGGM.
Congress or state legislatures could pass a law explicitly prohibiting
HGGM and imposing penalties on those who attempt it. Congress could
also enact prohibitions of limited duration, imposing “sunset clauses”
that would require reauthorization of the ban at some point in the
future.
The Food and Drug Administration (FDA) could articulate a policy not allowing clinical research using HGGM to proceed. While it appears that FDA has not yet received any proposals for HGGM, there may come a time when researchers seek FDA authorization for clinical research, and an explicit policy would provide clarity in such circumstances. Supporters of a U.S. ban on HGGM point to prohibitions enacted in other countries as examples of sound policy and would like to see Congress pass a similar law. Some suggest that an international approach would be preferable because it would provide the most comprehensive protection from changes to the human species, ensuring that countries would reinforce each other’s prohibition in this area.
The United Nations could play a role in implementing a ban through an international convention against HGGM. George Annas, a professor of law at Boston University, and others have drafted a “Convention on the Preservation of the Human Species” and have advocated for its adoption by the members of the United Nations. Such a treaty would ban “species-altering” activities, including human reproductive cloning and human germline genetic modification. This approach aims to preserve the “human species” globally by preventing scientists interested in pursuing these technologies from seeking a “home country” with the most permissive laws. However, a truly universal ban ultimately may be impossible: one country permitting the technology could provide a refuge for those who wish to develop or use HGGM.
Several critiques of the international approach have been raised. As a practical matter, it may be difficult to obtain support from a sufficient number of countries. Even those countries that do sign a treaty may not comply with it and there is limited ability to enforce these agreements because there are few international enforcement mechanisms. In addition, a one-size-fits-all policy ignores unique social and political characteristics that may dictate approaches that best fit a particular country.
One challenge to crafting an effective ban would be defining the technology at issue. Some countries have laws that purport to ban HGGM but leave enormous loopholes. For example, Finland’s law states: “Research on embryos and gametes for the purpose of developing procedures for modifying hereditary properties shall be prohibited, unless the research is for the purpose of curing or preventing a serious hereditary disease.” It is unclear when the exception for “curing or preventing a serious hereditary disease” would apply.
The challenges to instituting a ban on HGGM are significant but those who support a ban do not believe them insurmountable, particularly given the potential harms they foresee if HGGM is permitted.
An alternative to governmental prohibition is a voluntary agreement by scientists that they will not pursue germline genetic modification in humans. Such a consensus would be difficult to achieve and virtually impossible to enforce.
Oversight of HGGM could be aimed at ensuring the safety of the technology, its ethical use, or both.
Under current law, the FDA may have adequate authority to effectively oversee the safety of HGGM. The agency can require review and approval of an investigational new drug (IND) for any HGGM attempt, but deliberations are not open to the public. The agency could create an advisory committee specifically to inform its review of HGGM proposals. FDA advisory committees typically include researchers, clinicians, patients, caregivers, industry, and consumers and their meetings are open to the public. Creating such a committee to consider HGGM would give the public more access to the deliberations that inform FDA decision making, and would provide FDA with expert opinion and insight regarding the public’s concerns. FDA frequently makes use of such committees. For example, when scientists reported the birth of babies resulting from ooplasm transfer, FDA asked an advisory committee to consider this issue, and solicited presentations on ethics as well as safety and effectiveness.
With input from an advisory committee, FDA could develop additional guidance concerning the type of data they would require in an IND application to study HGGM. The issuance of guidance documents would be consistent with FDA’s approach to other developing technologies; indeed, FDA has issued numerous, progressively more detailed guidance documents for somatic gene therapy research to keep pace with new developments.
In addition, FDA could address the long-term outcomes of children born after HGGM and the well-being of future descendants. Longitudinal studies could be mandated federally as part of IND approval, and could receive federal funding as well. Such studies would provide critical data about potentially harmful effects of HGGM, but could raise confidentiality concerns, depending on how information is collected and maintained. In addition, the feasibility of following patients and their descendents for generations is uncertain, and current regulations would prohibit the government from mandating participation.
Any guidance FDA develops could clarify what human research subject protections it would apply to the area of HGGM and what standards Institutional Review Boards (IRB) should apply as well. Law professor Rebecca Dresser suggests that a new HGGM-specific human subjects research protection policy is needed.
In contrast to the FDA, whose processes and deliberations are largely private and focus primarily on safety and efficacy, the Recombinant DNA Advisory Committee's (RAC) deliberations are public and include consideration of other ethical and societal issues. However, the RAC’s current policy is not to consider germline proposals. If this policy were to change, the RAC could function as a forum for discussing the social and ethical issues raised by HGGM, as it has for somatic gene transfer research.
However, even if the RAC did consider germline proposals, it no longer has the authority to approve them, with the exception of those funded by National Institutes of Health (NIH.) Moreover, the RAC is inherently limited in its capacity to oversee research not funded by NIH. Thus some have suggested that an alternative oversight body may be necessary, particularly to consider ethical issues related to HGGM.
Chief among the ethical questions about HGGM, perhaps, is the purposes for which it should be permitted. For example, HGGM could be permitted for non-medical, enhancement reasons. Conversely, HGGM could be reserved only for illnesses that are fatal or deemed serious. An entity overseeing ethical use would need to consider and define what uses are permitted under what circumstances. Drawing these lines would be challenging and enforcement probably would be difficult. An oversight body would need to stay abreast of any new proposed uses and what their implications might be.
Numerous equity and justice concerns have been raised about HGGM’s impact on society. Many of these concerns implicate broader societal and policy issues and would be difficult to address through policy narrowly aimed at HGGM. Policymakers could, however, explore alternative approaches to address these concerns such as anti-discrimination laws, better access to medical treatment, more support for individuals and families dealing with genetic diseases, and other approaches to reduce the perceived need for HGGM and concerns about its negative impact on society. While some might argue that such indirect approaches could not address meaningfully the many societal issues that have been raised about HGGM, such reforms might provide broader societal benefits.
International bodies such as the United Nations also could play a role in the oversight of HGGM by convening interested stakeholders from around the world and considering possible international treaties or other restrictions aimed at guaranteeing safe and ethical use. However, most countries outside of the United States that have chosen to address the issue of HGGM have banned it entirely, making it unlikely they would agree to a less-restrictive international model. In addition, these international entities have limited ability to enforce such restrictions.
Finally, those interested in HGGM, including scientists and prospective parents, could develop voluntary guidelines for HGGM. Such guidelines, created in advance of the technology being ripe for consideration by FDA and/or RAC, could help guide its scientific development and proposed uses. However, given their voluntary nature, these guidelines are unlikely to satisfy those interested in enforceable governmental limits.
Questions remain about whether oversight of germline proposals should be treated any differently from somatic genetic modification by entities such as RAC or FDA, international bodies, voluntary societies, or a new entity in the future. On the one hand, germline modification could be seen as inherently suspect and have to overcome a presumption of being unsafe and/or unethical. On the other hand, the safety and ethical issues could be considered in the same manner and by the same oversight bodies that consider somatic proposals.
Under current law, the FDA may have adequate authority to effectively oversee the safety of HGGM. The agency can require review and approval of an investigational new drug (IND) for any HGGM attempt, but deliberations are not open to the public. The agency could create an advisory committee specifically to inform its review of HGGM proposals. FDA advisory committees typically include researchers, clinicians, patients, caregivers, industry, and consumers and their meetings are open to the public. Creating such a committee to consider HGGM would give the public more access to the deliberations that inform FDA decision making, and would provide FDA with expert opinion and insight regarding the public’s concerns. FDA frequently makes use of such committees. For example, when scientists reported the birth of babies resulting from ooplasm transfer, FDA asked an advisory committee to consider this issue, and solicited presentations on ethics as well as safety and effectiveness.
With input from an advisory committee, FDA could develop additional guidance concerning the type of data they would require in an IND application to study HGGM. The issuance of guidance documents would be consistent with FDA’s approach to other developing technologies; indeed, FDA has issued numerous, progressively more detailed guidance documents for somatic gene therapy research to keep pace with new developments.
In addition, FDA could address the long-term outcomes of children born after HGGM and the well-being of future descendants. Longitudinal studies could be mandated federally as part of IND approval, and could receive federal funding as well. Such studies would provide critical data about potentially harmful effects of HGGM, but could raise confidentiality concerns, depending on how information is collected and maintained. In addition, the feasibility of following patients and their descendents for generations is uncertain, and current regulations would prohibit the government from mandating participation.
Any guidance FDA develops could clarify what human research subject protections it would apply to the area of HGGM and what standards Institutional Review Boards (IRB) should apply as well. Law professor Rebecca Dresser suggests that a new HGGM-specific human subjects research protection policy is needed.
In contrast to the FDA, whose processes and deliberations are largely private and focus primarily on safety and efficacy, the Recombinant DNA Advisory Committee's (RAC) deliberations are public and include consideration of other ethical and societal issues. However, the RAC’s current policy is not to consider germline proposals. If this policy were to change, the RAC could function as a forum for discussing the social and ethical issues raised by HGGM, as it has for somatic gene transfer research.
However, even if the RAC did consider germline proposals, it no longer has the authority to approve them, with the exception of those funded by National Institutes of Health (NIH.) Moreover, the RAC is inherently limited in its capacity to oversee research not funded by NIH. Thus some have suggested that an alternative oversight body may be necessary, particularly to consider ethical issues related to HGGM.
Chief among the ethical questions about HGGM, perhaps, is the purposes for which it should be permitted. For example, HGGM could be permitted for non-medical, enhancement reasons. Conversely, HGGM could be reserved only for illnesses that are fatal or deemed serious. An entity overseeing ethical use would need to consider and define what uses are permitted under what circumstances. Drawing these lines would be challenging and enforcement probably would be difficult. An oversight body would need to stay abreast of any new proposed uses and what their implications might be.
Numerous equity and justice concerns have been raised about HGGM’s impact on society. Many of these concerns implicate broader societal and policy issues and would be difficult to address through policy narrowly aimed at HGGM. Policymakers could, however, explore alternative approaches to address these concerns such as anti-discrimination laws, better access to medical treatment, more support for individuals and families dealing with genetic diseases, and other approaches to reduce the perceived need for HGGM and concerns about its negative impact on society. While some might argue that such indirect approaches could not address meaningfully the many societal issues that have been raised about HGGM, such reforms might provide broader societal benefits.
International bodies such as the United Nations also could play a role in the oversight of HGGM by convening interested stakeholders from around the world and considering possible international treaties or other restrictions aimed at guaranteeing safe and ethical use. However, most countries outside of the United States that have chosen to address the issue of HGGM have banned it entirely, making it unlikely they would agree to a less-restrictive international model. In addition, these international entities have limited ability to enforce such restrictions.
Finally, those interested in HGGM, including scientists and prospective parents, could develop voluntary guidelines for HGGM. Such guidelines, created in advance of the technology being ripe for consideration by FDA and/or RAC, could help guide its scientific development and proposed uses. However, given their voluntary nature, these guidelines are unlikely to satisfy those interested in enforceable governmental limits.
Questions remain about whether oversight of germline proposals should be treated any differently from somatic genetic modification by entities such as RAC or FDA, international bodies, voluntary societies, or a new entity in the future. On the one hand, germline modification could be seen as inherently suspect and have to overcome a presumption of being unsafe and/or unethical. On the other hand, the safety and ethical issues could be considered in the same manner and by the same oversight bodies that consider somatic proposals.
Some believe that HGGM holds tremendous promise for preventing genetic
diseases and that society should pursue policies to promote or
encourage successful HGGM in the future. Currently, governmental
funding supports animal research that could be used to support an
application to investigate germline modification in humans. Although
not undertaken in pursuit of HGGM, this research provides data that has
helped overcome some of the technical obstacles to HGGM. Increased
funding for such research could provide additional data that could help
lead to HGGM in the future. In addition, policymakers could consider
funding research explicitly to advance HGGM techniques.
Excerpted from Human Germline Genetic Modification: Issues and Options for Policy Makers
with permission from The Genetics and Public Policy Center and The Pew Charitable Trusts.
with permission from The Genetics and Public Policy Center and The Pew Charitable Trusts.
