reprogenetics and public policy: reflections and recommendations

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EILEEN AGAR AUTOB IOGR APHY OF AN EMB R Y

ReprogeneticR eprogeneticsR eprogenetics

A SPECIAL S UP P LEMEN T TO THE HAS T I N GS C EN TER REP

and Public Policyand Public PolicyR E F L E C T I O N S A N D R E C O M M E N D A T I O N S

E R I K PA R E N S A N D L O R I P. KN O W L E Su


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ReprogeneticWorking Group MembersLori P. Knowles The Hastings CenterErik Parens The Hastings Center

Thomas Murray The Hastings Center

Timothy Caulfield University of Alberta, Edmonton, Canada

Chris Evans Harvard Medical SchoolDiane Scott-Jones Boston College

Diane B. Paul University of Massachusetts at Boston

Bartha Maria Knoppers Universite de Montreal, Montreal, Canada

Andrea L. Bonnicksen Northern Illinois University

Eric Juengst Case Western Reserve University

Gladys White Veterans Health Admistration/American Nurses Association

Kathi Hanna Science and Health Policy Consultant

Robert Cook-Deegan Duke University

Bonnie Steinbock University at Albany, State University of New York

Project ConsultantsAdrienne Asch Wellesley College

Patricia Baird University of British Columbia, Vancouver, Canada

Elizabeth Bartholet Harvard UniversityMark S. Frankel American Association for the Advancement of Science

Jamie Grifo New York University Medical Center

Andrew Grubb Cardiff University, United Kingdom

Ruth Hubbard Bilogical Laboratories, Harvard University

Itziar Alkorta Idiakez University of the Basque Country

Philip Noguchi Food and Drug Administration

John Robertson Law School, University of Texas

Susan Sherwin Dalhousie University, Halifax, Canada

Alison Harvison Young Queens University, Kingston, Canada

Research AssistantsSamantha Stokes

Michael Khair

Marguerite Strobel

Hastings Center LibrarianChris McKee

Art DirectorNora Porter

Hastings Center StaffMary Ann Hasbrouck

Jaime Ingraham

Sandra Morales

Vicki Peyton

Heather Alderman

Cover image: Autobiography of an Embryo, by Eileen Agar. Artists estate. Photo:

Tate Gallery, London / Art Resource, NY

S2 July-August 2003 / HASTINGS CENTER REPORT

Acknowledgments

This report is possible due in large part to the hard

work of our working group and project consultants.

We are further indebted to Robert Cook-Deegan,

Bruce Jennings, and Kathy Hudson, who offeredcomments on the penultimate draft of this report.Special thanks to Gregory Kaebnick for his many

contributions. While the opinions expressed in the

report are the authors, many ideas originated with

others. Mistakes are the responsibility of the authors.

This report is the product of a two-year project

conducted by The Hastings Center and funded by

The Greenwall Foundation. Additional funding was

provided by The Overbrook Foundation.

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t the first of the discussions that led eventual-ly to this report, a respected researcher-clini-cian in the world of reprogenetic medicine re-ferred to his field as one big embryo experi-ment. The phrase nicely captures what this

report is about. It is about the ethical issues and policychallenges that arise in the context of researchers and clin-

icians doing new things with embryos. The range of suchactivities is wide and growing: from studying embryos forthe sake of basic knowledge about developmental biology;to using them as sources of embryonic stem cells that canbe coaxed to cure disease; to creating, selecting, and alter-ing them for the sake of producing children. This reportfocuses on that last set of aims and emphasizes the needfor improved public oversighta need that grows moreurgent as reproductive and genetic medicine converge toproduce the new field of reprogenetics.1

For a variety of reasons, research involving the use, cre-ation, alteration, and storage of gametes and embryos issubject to little regulation in the United States. This situa-

tion is potentially dangerous. Unlike older in vitro fertil-ization (IVF) techniques, many new reprogenetic tech-niques make structural changes to cells,2 and with struc-tural changes arise concerns about the safety of the chil-dren produced by the technology. Further, both older andnewer techniques raise concerns about the safety of the

women who donate the eggs and the women in whom thefertilized eggs are implantedthe egg donors and the ges-tating mothers.

But concerns about reprogenetics are not only aboutsafety. Just as important are concerns about the well-beingof children produced by these techniquesand about the

well-being of the families and society that will welcome

those children. Are we in danger of allowing the marketmentality to colonize childbearing, as it has already colo-nized so much of our lives? Could the proliferation oftechniques that increasingly enable us not just to havechildren, but to choose characteristics unrelated to theirhealth, exacerbate our tendency to think of children as theobjects of our making? Could these techniques lead us tothink of ourselves as mechanisms that are valued for ourindividual parts or traits rather than as individuals who arevalued for being unique wholes? Could it aggravate some

forms of unfairness, or complicity with unjust norms?3 Putpositively, what can we do to increase the chances thatthese techniques are used in ways that further the happi-ness of children, familiesand ultimately the well-beingof our society as a whole?

The answers to these questions will rest on fundamen-tal beliefs and commitments to such values as liberty,

equality, solidarity, and justice. They will likely be com-plex and will sometimes reveal deep disagreements. Butsuch disagreement should not stand in the way of tryingto talk together about matters of such great importance.

We, the authors of this document, cannot help buthave views of our own about some of these contestedquestions. But our primary purpose is not to defend thoseviews. Rather, we wish chiefly to establish that our societyneeds to find better ways to grapple withand regulatereprogenetic activities. The future of reprogenetic practiceis too important to be decided solely by the market. Wecall for the creation of an oversight structure that willmake possible a thorough and transparent policy discus-

sion of reprogenetics and effective regulation of those fa-cilities involved in reprogenetic research and services.

The report is divided into five parts: In the first, we de-lineate what we mean by reprogenetics. In the second, weidentify some of the ethical concerns that commentatorshave broached about reprogenetics and argue that ques-tions about well-being must be part of the policy conver-sation. Part three describes the historical roots of our cur-rent oversight situation. Reproductive medicine and ge-netics have long been overseen separatelyand with verydifferent degrees of care. The politics of abortion havelargely prevented any effective oversight of reproductivemedicine. But as reproductive medicine and genetics con-

verge, the current state of affairs does not allow us as a so-ciety to anticipate and contemplate the emerging reproge-netic picture in all of its complexity.

To shed light on what a better approach to reprogenet-ics policy in this country might look like, part four brieflyexplores the weaknesses and strengths of the regulatory ap-proaches adopted by the United Kingdom and Canada.The final part sketches a proposal for an oversight bodythat can respond to the technological and ethical realitiesof reprogenetics in this country.

S3SPECIAL SUPPLEMENT / Reprogenetics and Pulic Policy: Reflections and Recommendations

REPROGENETICS AND PUBLIC POLICY

u R E F L E C T I O N S A N D R E C O M M E N D A T I O N S t

b y E R I K PA R E N S A N D L O R I P. KN O W L E S

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P A R T O N E

What Is Reprogenetics?

his report defines reprogeneticsbroadly, asthe field of research and application thatinvolves the creation, use, manipulation,

or storage of gametes or embryos. The report also definesembryo broadly. It adopts the definition that Congress usesin its ban on funding for embryo research: any organism. . . that is derived by fertilization, parthenogenesis,cloning, or any other means from one or more human ga-metes or human diploid cells.4 Of course, there are alter-native definitions that reflect the choices a society makes.5

The techniques used to create, use, and manipulateembryos for reproductive purposes can also be put to non-reproductive purposes. For example, the somatic cell nu-clear transfer (SCNT) or cloning technique can be used,in principle, for the reproductive purpose of creating achild or for the nonreproductive purpose of creating asource of embryonic stem (ES) cells (and ultimately trans-plantable tissue). Because the reproductive and nonrepro-ductive uses of embryos are inextricably entwined, wemust consider them together if we want to understandand anticipate the implications of our big embryo exper-iment.

This broad understanding of reprogeneticsall inter-ventions involved in the creation, use, manipulation, orstorage of gametes and embryosdelimits a fairly distinct

class of interventions. Reprogenetic research and practiceinclude interventions aimed at creating embryos, whetherfor reproductive or therapeutic purposes, and whether bytraditional means such as IVF or by newer means suchas SCNT or intracytoplasmic sperm injection (ICSI). Alsoincluded are interventions aimed at altering gametes orembryos, whether by the traditional techniques of re-combinant DNA or by the newer techniques involvingcellular surgery or the use of artificial chromosomes. (In-terventions aimed at transferring genes to somaticcells tocure individuals of disease are plainly excluded.)

The scope of reprogenetics, and correspondingly of thisreport, could have been broadened still further to include

surrogacy arrangements and prenatal testing. Ultimately,following the example set by the mandate of the UnitedKingdoms Human Fertilisation and Embryology Author-ity, it excludesall interventions on embryos and fetuses in-sidea womans body.6 Research on and treatment of em-bryos and fetuses that are in a womans body are regulatedto differing extents by regulations for human subjects re-search and by statutory and common law.7Also, a concep-tion of reprogenetics broad enough to encompass theseother domains would threaten to grow unwieldy.

Alternatively, the scope of the reprogenetics could havebeen limited to those techniques that involve emergingtechnologies. This narrower conception of reprogenetics,however, would make it impossible to contemplate thebigger reprogenetic picturethe ways in which reproduc-tive and genetic technologies are converging. Of course,future discussions may identify different ways of delimit-ing the scope of reprogenetics. Such discussions should beencouraged.

Reprogenetics in Action

The past few years have provided several opportunitiesto notice the very different purposes to which we can

put our growing capacity to do things with gametes andembryosto notice the very different ways in which re-productive research and practice converge with genetic re-search and practice.

n In September 1998, news broke about a technologythat can sort sperm according to the weight of the chro-mosomes they carry with an accuracy rate of approximate-ly 85 percent.8 The company that developed this technol-ogy markets it to couples that desire to select the sex oftheir children. Today approximately 430 children have

been born using this technique.9

n Molly Nash was afflicted with Fanconis anemia. Herparents wanted to have a second child who would not beafflicted with Fanconis, and who also could be a histo-compatible donor to Mollya source of compatible cordblood. To help the Nashes have such a child, researcher-clinicians used preimplantation genetic diagnosisgenet-ic diagnosis of embryos created in a laboratory to identifysuitable embryos for transfer to Mollys mothers uterus. Achild who was both free of disease and histocompatible

with Molly was born in August 2000.10

n In March of 2001, researchers at the Institute for Re-productive Medicine and Science at Saint Barnabus an-nounced that an experimental technique had helped ap-proximately twenty women become pregnant. These

women had previously been unable to conceive as the re-sult of defects in their eggs cytoplasmthe ooplasm.The researchers performed ooplasm transplantation byinjecting healthy ooplasm from donor eggs into defectiveones. Because the ooplasm contains tiny organelles calledmitochondria, and because each mitochondrion containsa small loop of DNA, ooplasm transplantation entails the

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transfer of genetic material from one egg to the other. In-deed, the researchers announced that they had achievedthe first successful germ-line modification and that ithad resulted in apparently healthy babies.11

n To date, much of the public and policy conversationabout research on embryonic stem cells (ES cells) has fo-cused rather narrowly on the moral status of embryos andthe potential of ES cells to be put to the therapeutic pur-pose of creating transplantable tissue. If the ES cells werecreated through SCNT techniques, they could be used togenerate transplantable tissue that was fully histocompati-ble with the person who received it. Largely missing from

this discussion has been a recognition that, in theory, EScell research could be combined with both SCNT andgene transfer techniques for the reproductive purpose ofcreating either healthy or enhanced embryosand chil-dren.12

These four examples suggest some of the ways in whichreproductive and genetic technologies are coming togetherto increase our capacity to prevent or cure diseaseand tocreate children with traits we desire, some of which are re-lated to health, others of which may not be. IVF can helpprospective parents have a childwhatever child they get

in the genetic lottery. The newer techniques go one stepfurther: they promise to help prospective parents choose

what kind of child they getor at least to increase thechancesthat their children will have some traits rather thanothers. Some of those traits will be related to the health ofsomeone other than the childlike Molly Nashs brother,

Adam. Other traits, someday, may be related not to any-ones health, but to some perceived advantage. 13

It is altogether too early in our understanding of the ge-netics of complex traits to know how far the project ofenhancing children can go, in good part because com-plex traits appear to involve extremely complex interac-tions among many genes and environmental factors.14 But

even if adding genetic material (whether genes or artificialchromosomes) to embryos to enhance human traits doesnot prove feasible, we are likely to learn enough aboutgenotype-phenotype relationships that some entrepre-neurial individuals will promise that they can at least in-crease the chances of having a child with some desiredtrait, even if the child is created merely through IVF andpreimplantation genetic diagnosis rather than throughSCNT and gene transfer. We are just beginning to explore

what that new power may mean for the well-being of chil-dren, parents, and society as a whole.15

uuuDreaming of Offspring,Paul Klee 2003 Artists Rights Society

(ARS), NY / VG Bild-Kunst,

Bonn; Photo: Erich Lessing /

Art Resource, NY


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he convergence of reproductive and genetictechnologies raises complex and sometimesprofound ethical questions that call out forinformed policy, publicly and transparently

developed. Some of these questions are about tangibleharms; others, however, are about non-tangible harms.Into the first category fall concerns about the safety of the

women who provide oocytes as well as the safety of thegestating mothers and of the children produced. The sec-ond includes broader concerns about human well-being.

Although some of the reprogenetics technologies are in-creasingly thought to be within the purview of the Foodand Drug Administration, the FDA is not mandated toconsider well-being concerns.

Well-being concerns are not all equally persuasive forall commentators. It is not the goal of this report to defendthem all, howevernor to defend exactly our way of ar-ticulating or organizing them. Delineating a representativerange of these concerns is enough to establish the need fora transparent policy discussion of reprogenetics. That dis-cussion will allow us to accept or reject the various con-cerns that commentators have broached. Yet given theconcerns, we should not forego that discussion and leaveregulation to the market alone.

Safety

In reproductive medicine, more than in most other areasof medical practice, the line between clinical innovationand human experimentation is fuzzy: patients in repro-ductive medicine sometimes can be subjected to the highlevels of uncertainty and risk commonly associated withbeing a research subject.16 Consequently, reprogeneticsraises concerns about the safety of the women, children,and tissue providers who are involved in reproductivemedicine. As in all scientific experimentation, it is impor-tant to be realistic about the nature of scientific uncertain-ty. Although researchers and clinicians are often confident

that they can predict what the outcomes of a particulartechnique may be, in fact we often cannot reliably predictthe outcomes. We must expect the unexpected. At thevery least we need adequate testing and record keeping toapproach the standard of scientific research mandated inother areas of research.

The newer reprogenetic techniques raise a number ofunresolved safety concerns.17 The potential health risks tochildren who might be created by means of cloning tech-nologies have been widely publicized.18 In addition, it re-mains unknown how safe and effective ooplasm trans-

plantation is. There is some evidence to suggest thatooplasm transplantation may involve an increased risk ofaneuploidy (that is, having an atypical number of chro-mosomes), although the clinical data are too incompleteto support any clear conclusions.19 But safety concerns areof course not limited to the newer reprogenetic technolo-gies. Insofar as traditional IVF often produces multiplebirths, babies born by such methods are at increased riskof prematurity, low birth weight, infant death, and life-long disability.20 Recent studies have suggested that chil-dren produced by means of intracytoplasmic sperm injec-tion may be at an increased risk of aneuploidy. 21

Reprogenetic technologies often require a supply ofeggs from either the patient or from donors (who actu-ally often sell their eggs or provide them in exchange forfertility services). New technologies like ooplasm trans-plantation and ES cell research will only increase the de-mand for oocytes. The risks to women who provide eggsare associated primarily with the drugs used to induce su-perovulation. Severe ovarian hyperstimulation syndromeis a rare but life-threatening event. A potential increase inthe risk of ovarian cancer is also thought to be associated

with superovulation. In addition to the drug-related risks,there are also some surgical risks, including possiblepuncture of the fallopian tubes, infection or bleeding.22

Traditional assisted-reproductive techniques also put ges-tating women at increased risk of preeclampsia, diabetesmellitus, bleeding, and anemia.23 In addition to risks asso-ciated with the drugs and surgical techniques, women andchildren are also at increased risk of the infections that ac-company tissue (including egg or sperm) transplantation.

In discussing safety-related risks, it is important to re-member that the couples seeking to have children withthese techniques are often more than willing to bear them.There is, however, an ethical consensus that parents have aprima facie obligation to shield their prospective childrenfrom preventable impairments.24 Needless to say, an oblig-ation to shield children from preventable, reprogenetically

induced impairments must be balanced against theparental right to try to create a child. In other words, par-ents must balance their desire to create a child with theirdesire to shield the child from preventable harms.

How best to balance those competing values and de-sires is open to debate, and oversimplified generalizationsabout what individuals want and what they owe eachother are not adequate to help us understand the complexrelationships and motivations that are inherent in goodfamily life. Everyone can agree, however, that there is a


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Whats at Stake?


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need for good data about the real risks inherent in thesetechnologies.

Unfortunately, experimental reprogenetic techniqueshave been rapidly introduced on the market without suf-ficient prior animal experimentation, randomized clinicaltrials, or the rigorous data collection that would occur infederally funded studies.25 In fact, ooplasm transplanta-

tion was advertised on the Internet before the Food andDrug Administration intervened to collect informationand conduct hearings on the techniques safety and effica-cy.26Without good data, no one can give meaningful in-formed consent to engage in such activities, no matterhow important the aim of having a child.

Well-Being

Public policy in the field of reprogenetics is more chal-lenging than in some other domains because, even ifall the safety concerns were addressed, other vital concerns

would remain. Given the depth and complexity of the de-sire to have a biologically related child, the techniquesused to gratify that desire can raise equally deep and com-plex questions about human well-being.

Arguably, many well-being concerns are facets of thesame fundamental worry that, in a consumer culture suchas ours, using technology to produce better children willdrive us toward making the fundamental mistake of treat-ing childrenand the rest of usas commodities ratherthan as persons.27Whereas we think it appropriate to givea price to commodities, we think it is a category mistaketo give a price to children; to do so is to miss that the sortof being were dealing with is priceless.28 Insofar as re-

progenetic practices will promote the view that the valueof gametes, embryos, or children depends on their partic-ular traits, those practices will raise similar concerns.

Skeptics sometimes claim that such concerns concealnothing more than fear of the new.29 Very likely they canbe a sign of fear, but they can also reflect a desire to affirmthe intrinsic value of the diversity of human forms. Well-being concerns are, in part, about the fact that reprogenet-ic technologies are being used, not by persons who aim toshape themselves, but rather by parents who aim to shapetheir children. Using reprogenetic means for this goal mayexacerbate parents tendencies to think of children as theobjects of their making and to have unrealistic expecta-

tions of their children. Well-being concerns are also, inpart, about the belief that in using reprogenetic means toshape children, we are expressing a problematic concep-tion of what it is to be a human being.30 The worry is thatin using these means we will lose sight of the fact that chil-dren are wholes who cannot be reduced to the sum oftheir traits if we are to adequately understand what theyare.

Another source of concern is the prospect that wemight someday use reprogenetic means to enhancechil-drens traits. If we presume that access to such enhance-

ments is unequal, then there is reason to worry that par-ents who already purchase social advantages will be able,in effect, to purchase genetic capacities to use those ad-vantagesthereby potentially increasing the gap betweenthe haves and have-nots.31 Imagine that the teenager al-ready blessed with social advantages like Stanley Kaplanprep courses has already been outfitted at birth with a re-

progenetic form of Ritalinwith the capacity to be espe-cially good at exploiting social advantages like the prepcourses. That children with advantages are already usingpsychopharmacological agents in just that way is hardly anargument for permitting reprogenetic means to achievemore of the same. Nor can we regard the decision to usereprogenetic means as a private choice, for such choices

would generate pressures on others to follow suit. Someparents will no doubt fervently want to acquire such ad-vantages for their prospective children, yet if they obtainthem, other parents will likely feel pressured, perhaps evenobligated, to purchase the same services for their chil-dren.32

If we assume instead that all parents have equal accessto new enhancements for their children, concerns about

justice still do not disappear. Some commentators arguethat if we approved general use of reprogenetic enhance-ments, we might then begin to use reprogenetic means tosolve complex social problems, and in so doing undermineour commitments to equality and diversity; prospectiveparents might use the technology to increase the chancesthat their children will better live up to dominant ideals,

which at least in some cases will be unjust.33 Imagine anintervention that increases the chances that a child willhave the pale pigmentation currently valorized in the

West; although we might readily imagine why parentswould want to insulate their children from the norm thatvalues pale pigmentation, we might nonetheless worrythat using reprogenetics to deal with discrimination leavesthe unjust norms in place.

Still other concerns center on the well-being of thewomen who will provide the eggs, whether for research orfor reproduction. As has been articulated in a parallel fash-ion in the debate over the ethics of commercial surrogatepregnancy,34 these women seem to be candidates for coer-cion and exploitation. The potential for exploitation is ag-gravated when the phenotype of the woman providing theeggs is irrelevant. In those cases, the woman may be espe-

cially vulnerable to economic coercion. Although highprices are reportedly sometimes offered for college

womens eggs, researchers will likely seek a cheaper sourceof oocytes for techniques such as therapeutic ES cell re-search and ooplasm transplantation. Many of the women

who undergo hyperstimulation and surgical removal ofoocytes for research purposes would likely do so becausethey need the money, yet they would likely not be as wellplaced to protect themselves. Just as we do not encouragethe buying and selling of organs because such a market



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could exploit the poor, we should be wary of a market inhuman reproductive materials.35

There are other long-standing questions about the ef-fects such commercialization of reproduction will have on

us as a society.36

One reason many argue that commercial-ization of human reproduction should be avoided is thatthey object to putting a price on something priceless, torendering it open to comparison and to bargaining.37

Some also argue that we lose something important by re-placing gift relationships with market exchanges.38 Al-though markets already exist in a number of humangoods intimately tied to our personhood, such as humanlabor and human beauty, there need not be markets in allsuch goods. We need these issues to be part of the dis-cussion that informs reprogenetics policymaking, ratherthan fatalistically accepting the colonization of children-and family-making by the market.

The Controversy over Well-being

In the U.S. public policy debate, concerns such as theones mentioned above have often been viewed by somecommentators with skepticism, if not derision. They aresometimes referred to as symbolic, speculative,vague, and sometimes religious.39Yet even ardent crit-ics of these concerns still accord them weight. For exam-ple, John Robertson, one of the strongest proponents ofprocreative liberty, acknowledges that [a]t a certain point

. . . a practice such as cloning, enhancement,or intentional diminishment of offspringmay be so far removed from even pluralisticnotions of reproductive meaning that theyleave the realm of protected reproductivechoice.40 Robertson understands that if weare to place limits on procreative liberty,then there is no way around the difficult

work of taking well-being concerns serious-ly.

Similarly, Dr. Charles Strom, who usedpreimplantation genetic diagnosis to help Molly Nashsfamily produce a histocompatible sibling without Fan-conis anemia, recognizes that PGD could also be used totest for non-health related traits, and he appears to have

concerns about some of those uses. He told a New YorkTimes Magazinereporter that reprogenetics research of thesort he himself conducts has all been forced into the pri-vate sector . . . where there are no controls. He added,There should be limits. It is up to us, as a society, to de-cide what they are.41 It is important to note that Stromscall for controls and limits is not based on concerns aboutsafety alone.

It will not be easy to fully articulate the limits thatshould be placed on these technologies. But if we are tohave any limits, then we as a society will have to find a lan-guage in which to articulate them.

Though making public policy based on well-being

concerns will be difficult, it will not be without precedent.We already allow questions about the well-being of indi-vidual children to guide some reproductive decisions. Forexample, the state considers the well-being of children inadoption decisions.42 Before prospective parents are per-mitted to adopt a child, they are required to provide evi-dence that they would be good parents. What constitutesa good parent is far from obvious, and making such judg-ments is difficult, but that does not prevent us from mak-ing such determinations.


uuuThe Newborn, Constantin Brancusi 2003 Artists Rights Society (ARS), NY /

ADAGP, Paris; Digital Image The Museum of

Modern Art/Licensed by SCALA / Art Resource,

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Indeed, the New York State Task Force on Life and theLaw has suggested that physicians are entitled to consid-er the welfare of any child who might be born as a resultof reproductive and genetic procedures.43 Although thetask force staunchly supports procreative liberty, it does, inthe name of child welfare, identify circumstances that may

warrant refusing prospective parents access to assisted-re-

productive services.44 Consequently, despite a general re-luctance to address well-being issues in reproductive poli-cy, there are precedents for defining limits to procreativeliberty in the name of child welfare in public policy.45

Similar judgments could be made to define limits to thecircumstances in which reprogenetic technologies areused.

Theres no denying that we hold dear different andsometimes competing fundamental values, including lib-erty, equality, solidarity, and justice. When those valuescome into conflict, we in the United States generally pre-fer to allow individuals to resolve the conflict them-selvesto exercise their individual liberty and choose forthemselves. But we do not always leave it to individualsalone to resolve conflicts between values. For example, wehave decided as a matter of public policy that people can-not buy and sell other people. In this case, equality trumpsfreedom. Similarly, we prohibit a market in organs be-cause such a market would undermine some values that

we esteem even more than we esteem an individuals liber-ty to buy and sell what she wants. We have decided, in-stead, to rely on the altruism of donors, even thoughdonors do not meet the demand for organs, because doingso furthers the ethical commitments of our society. 46

Absent systematic regulation, reprogenetic technologies

are limited mainly by the constraints of the market andthe piecemeal constraints of professional self-regulation.The extent to which reproductive decisions, materials, andtechniques should be left to the market should be part ofour public policy discussion. Though no one would dareplace an ad for a kidney, much less a child, in a collegenewspaper, ads are placed in university papers to induceyoung women with particular traits to sell their eggs foruse in IVF.47And, as mentioned earlier, it is now possiblein this country to purchase an increased chance that you

will get a baby with the sex you prefer.48 Most countrieswith similar cultures have prohibited sex selection that isunrelated to disease prevention.49 Indeed, many countries

hold that markets in human reproductive tissues, tech-nologies, and services are simply blocked exchanges,50 orhors du commerce.51 The United Nations UniversalDeclaration on the Human Genome and Human Rightsasserts that civilized societies must avoid putting a priceon human reproduction.

Embryo Research

Most western industrialized countries share a viewthat embryos in petri dishes are neither persons normere property.52 Insofar as embryos could become personsif they were transferred from petri dishes into wombs, theydeserve our respect; how much respect the entity deservesdepends in part on how far along the developmental pathit is. The farther along the path it is, the more respect itdeserves. We express that respect with prohibitions andlimits that restrict the uses and conditions under whichembryos may be used in research.53 But many think thatsome research is acceptable. Long before reproductive spe-cialists were creating and manipulating embryos to pro-duce children, they had to conduct experiments on em-bryos, which no one would have dreamed of implantingin a woman. IVF would never have gotten off the ground

without embryo experimentation.Yet even if many people agree that at least some em-

bryo research is ethically permissible, many questions re-main about what it means for us to use embryos to serveour purposes. Will a given technique or manner or pur-pose of embryo research express appropriate respect forthese entities? Or will it incline us to think of embryos asmere stuff to put to whatever purposes we see fit? Will

our activities involving embryos incline us to treat theseentities as mere instruments for pursuing other goalsand will doing so affect how we understand our relation-ships to each other and, ultimately, our relationships tothe rest of the natural world? All of those questions are ul-timately about the well-being of individuals and our soci-ety as a whole.

Other countries have struggled to think about these is-sues at a policy level and make clear the ethical commit-ments that underlie their embryo research policies. Wemust do the same. The overall task, therefore, is to designan oversight system that allows debate about both safetyand well-being to inform responsible reprogenetics policy.


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he current public policy stance regardingreprogenetic technologies is a compro-mise and a patchwork, derived from deepdivides in American politics and the acci-

dents of scientific progress. It is riddled with redundan-cies, inconsistencies, gaps, and inefficiencies. The politicaldivision that has hampered public policy on reprogeneticsis rooted in the vitriolic U.S. debate over abortion. Giventhe polarizing dynamics of this debate, much of the pub-lic policy conversation about embryo research and repro-ductive policy has consisted of pro-choice and anti-abor-tion activists shouting past each other. Unsurprisingly,many policymakers have chosen to avoid entering thatfray, and they have therefore not been able to agree thatsome embryo research is acceptable for some purposes,but not for others. As a result, almost all embryo researchhas been driven into the private sector. The natural secre-cy of the private sector can have two results: it can impedethe progression of the science given the need for confiden-tiality, 54 and it can reduce the publics role in deliberatingabout the direction of the science. For the bulk of such

work to go on in the shadowlands of the private sector55

can be both dangerous for participants and incompatible with the ideal of conducting such work in the light of

forthright public deliberation.The second reason we lack a productive public conver-sation about reprogenetics has to do with the historicalfact that until very recently, reproductive medicine and ge-netic medicine have been separate lines of inquiry, pur-sued by professionals with training in quite independentscientific and medical fields. Even if genetic and reproduc-tive technologies were not in the midst of converging, theredundancies, inconsistencies, gaps, and inefficiencies inthe current systems of oversight for genetic and, especially,for reproductive medicine would call out for reform. Butgenetic and reproductive technologies are converging. Anew system to oversee reprogenetic research and services is

needed, therefore, for functional reasons, since the old cat-egories of genetics and reproductive research do notreflect the new technological realities. The ooplasm trans-plantation protocol (see page S4) is a prime example of anintervention that does not fit cleanly into either of the oldcategories: the purpose is reproductive, but achieving itentails a genetic change.

Converging Lines of Research

In the mid-1970s, when research into reproduction andgenetics was getting off the ground in earnest, the twofields appeared largely unrelated. Reproductive medicinehad begun to promise that IVF could help infertile cou-ples have children. There really was no genetic medicine,

just genetic researchers dreaming of curing terrible dis-eases. The possibility of genetically modifying gametesand embryos was quickly dismissed, citing a consensusthat our society would never embark upon making suchchanges. The ethical and technical barriers, it was regular-ly asserted, were simply too high.56

At that time, the two fields were overseen in quite dif-ferent ways. Gene transfer research underwent intense reg-ulatory oversight and became the subject of a well-devel-oped policy conversation about its purposes; reproductivemedicine has received much less careful attention.

GENETICS. The National Institute of Healths Recom-binant DNA Advisory Committee (the RAC) was createdin 1974 in part to be a forum for better public conversa-tion about genetics research. In the beginning, RAC was aforum to discuss concerns about the safety of splicing for-

eign genes into microorganisms. In 1982, the report Splic-ing Life, produced by the Presidents Commission for theStudy of Ethical Problems in Medicine and Biomedicaland Behavioral Research, argued that RACs purviewshould be expanded to include gene transfer protocols inhumans and that its membership should be expanded toinclude, among others, lay public participants, and ethi-cists.57 In 1985, when RAC adopted guidelines for re-searchers proposing to embark upon gene transfer experi-ments in humans, it was responsible for making recom-mendations to the NIH director about protocol approvaland for promoting a public conversation about the pur-poses of such research. It became, therefore, a place to dis-

cuss questions about both safety and well-being. Eventhough researchers in the private sector were not requiredby law to put their protocols before RAC, they did so vol-untarilyat least until 1996.

In 1996, NIH director Harold Varmus announced thathe would eliminate RAC. He argued that because thebasic issues surrounding gene transfer research had beenresolved, RAC oversight was redundant.58When observersresponded that RAC was needed more than ever becauseof the prospect of germ-line modification and genetic en-hancement, Varmus revised his recommendation to elimi-

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nate RAC. He left it standing, but took away its power toapprove protocols, opting instead to rely on a system ofIRB and FDA oversight.

While there are redundancies and even some inconsis-tencies between RAC and FDA oversight of genetics re-search,59 together at least they provide mechanisms forbroaching both safety and well-being issues. Further, most

genetics research carried out in the private sector is over-seen by the FDA, and private sector genetics research isoften voluntarily taken before RAC if researchers or theirsponsors think they are broaching a novel issue.

Unfortunately, however, RACs guidelines describe itsmandate in terms of the technology that was around in the1980s; it considers only those interventions that involverecombinant DNA.60 Thus the ooplasm transplantationprotocol technically fell outside of RACs purview, eventhough it involved inheritable genetic modifications, be-cause the protocol employed cellular surgery rather thanrecombinant DNA. It was only that technological detailthat kept the protocol, which the researchers themselvescalled the first successful human germline genetic modifi-cation, from being subject to RAC scrutiny.61And thusthat research was conducted without public conversation,under the supervision only of the researchers and of theirinstitutions IRB.

The lack of a comprehensive, informed oversight sys-tem means that researchers in reprogenetics risk violatingtwo critical moral obligations, one to individuals and oneto society. The first is the researchers obligation to avoidharming individuals. Researcher-clinicians are obliged torefrain from offering techniques to produce children untilthe techniques have been shown to pose minimal risks to

such children. But many reprogenetic techniques have notyet been shown to pose such minimal risks. In theooplasm transplantation protocol, the researchers ac-knowledged that the long-term effects of the interventionare simply not known.62 Indeed, two of the fourteen fetus-es they produced had Turners syndrome.63 (One sponta-neously aborted and the other was selectively aborted.)Turners is not an uncommon genetic disorder, and theTurners births may not have been caused by the proce-dure; or, they may have. Researchers and clinicians hereand abroad expressed concern that such risks were taken

with little understanding of the long-term health conse-quences.64 Similar safety concerns have surrounded the use

of ICSI.65 The potential danger of such procedures callsout for a public system of oversight that relies on morethan the discretion of individual researchers and their in-stitutions.

Second, since scientists are members of a democraticcommunity who share resources (and all researchers in thiscountry benefit directly or indirectly from our extraordi-nary scientific infrastructure), they are obliged to subjecttheir research to public scrutiny, especially if the researchpromises to affect future children and thus the future ofour society. That obligation is embodied in the RAC. But

the ooplasm transplantation protocol ran afoul of the spir-it of this obligation. The decision to make inheritable ge-netic modifications in the human genome should not beleft to individuals. It should be made at a policy level afterpublic discussion about both safety and well-being con-cerns.66

REPRODUCTIVE MEDICINE. In contrast to geneticresearch, reproductive research in the United States goeson with relatively little public scrutiny. The National Con-ference of State Legislatures recently summed up the cur-rent system of regulation in this country when it wrote:[A] substantial proportion of research and innovativetherapy in reproductive medicine need not be subject topeer review, may not conform to current standards for in-formed consent, and may be offering services that havenever been fully evaluated for safety and efficiency.67 Thisminimalist approach is in stark contrast to that taken inmuch of the rest of the democratic world.68

The history of the oversight of reproductive medicine isheavily influenced by the dynamics of the abortion debate.Those dynamics make policymakers reluctant to engage ina discussion about embryo research. In the late 1970s, theEthics Advisory Board (EAB), which was appointed by theCarter administration, endorsed the idea of federal sup-port for embryo research. According to the EAB guide-lines, federally funded embryo research had to be reviewedby the EAB. Thus, when under Carter, Reagan, and BushSr., funding for the EAB was denied, the result was a defacto ban on federally funded embryo research. TheHealth Research Extension Act of 1985 precluded embryoresearch not intended to benefit the particular embryo.69

In 1993, however, with the arrival of the Clinton adminis-tration, Congress nullified the EAB-approval requirementand temporarily ended the ban.70

Also in 1993, NIH director Harold Varmus created theHuman Embryo Research Panel (HERP) to give him ad-vice regarding what kinds of embryo research NIH oughtto fund. In 1994, HERP endorsed funding for embryo re-search, including funds for some creation of embryos. Pre-sciently, HERP argued that if ES cells were ever isolated inhumans, ES cell research would be one form of embryo re-search that should be eligible for federal funding. Al-though Clinton rejected HERPs recommendation withrespect to funding the creation of embryos for research, he

otherwise endorsed the HERP report. In 1995, in reactionto HERP and Clinton, Congress passed the Dickey-Wick-er amendment, which precludes federal funding of em-bryo research through annual NIH Appropriation Acts.71

Consequently, where embryo research goes on, it does sowithout public money or scrutinyin the private sector.72

Another part of the explanation for the current lack ofoversight of reproductive medicine is that many new in-terventions in the field are considered innovative applica-tionnot researchby those who offer them. And sincethey are presented as innovative clinical practice rather



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than as research, oversight of them is left to the discretionof the individuals or institutions offering them.

Moreover, because most insurance companies still do

not pay for infertility services, they have not insisted onscrutinizing the results of reproductive research in the waythey scrutinize other forms of medical research. And be-cause patients often accept that the failure rate of repro-ductive interventions is high, malpractice litigation hasnot effectively brought legal scrutiny to the field. 73

None of this is to say that reproductive research andservices go on without any oversight or regulation. Vir-ginia and New Hampshire have comprehensive legislationregarding assisted reproduction,74 and many states havelaws regulating some aspects of, or techniques used in, em-bryo research.75 At the federal level, the 1992 Congres-sional Fertility Clinic Success Rate and Certification Act

(FCSRCA) requires clinics offering assisted reproductiontechnologies to disclose pregnancy success rates to theCenters for Disease Control. And laboratories that per-form the diagnostic tests related to assisted reproduction,such as semen or hormonal analysis, must be certifiedunder the federal Clinical Laboratories Improvement Act(CLIA).76

Professional organizations in reproductive medicinehave also set practice standards. The American Society forReproductive Medicine (ASRM) set practice standards forIVF, GIFT, and related procedures in 1998.77ASRM also

created guidelines for gamete

and embryo donation in 1998,and revised them in 2002.78

Members of ASRMs Societyfor Assisted Reproductive Tech-nologies (SART), who accountfor as many as 90 percent of theproviders of reproductive ser-vices, comply with FCSRCA,allow inspections, run accredit-ed embryology laboratories,and follow the ethical guide-lines of ASRM.

Finally, the FDA has assert-ed its jurisdiction over cloningand ooplasm transplantationon grounds that such interven-tions create products analo-gous to the biologic productsalready within its mandate(gene-therapy products, for ex-ample).79 Given that the FDAsmandate is limited to the con-

sideration of issues related to safety and efficacy, thereforeleaving out concerns about well-being, it would be best iftechnologies like cloning and ooplasm transplantation did

not fall exclusively within FDAs mandate.Presidential bioethics advisory commissions have takenup both the safety and well-being issues raised by certaintechnologies involving embryoscloning and stem cellresearchbut only on an ad hoc basis. The modusoperandi of President Clintons National Bioethics Adviso-ry Commission (NBAC) was to respond to the presidentsspecific requests, which made it difficult to consider thefull reprogenetic picture. President Bushs PresidentsCouncil on Bioethics (PCB) recently issued an advisoryreport on the use of cloning technology, 80 but like NBAC,its resources and mandate are limited, it will likely be re-placed by a change in presidents, and its role is purely ad-

visory. Consequently, the NBAC and PCB reports willlikely join the thoughtful, articulate advisory reports thatform part of this countrys academic bioethics work, butnot part of its public policy.

In sum, many groups, commissions, and federal agen-cies have commented on or asserted authority over variousaspects of reproductive services and research, yet there is,at best, a patchwork system of oversight. There is nostanding body to promote public conversation about boththe safety and well-being issues that arise in the context ofnew reproductive technologies.



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EMBRYONIC STEM CELLS: A CRITICAL MOMENT.

We are at a critical and perhaps a propitious juncture inthe development of reprogenetics and in the history of thedebates over embryo research. Research on embryonicstem cells (ES cells) occurs at the convergence of repro-ductive and genetics technologies. That convergencebrings promise and peril, which may prove vivid enough

to make both sides of the abortion debate contemplate acompromise regarding embryo research.

It is widely known both that research on embryonicstem cells (ES cells) holds the promise of producing trans-plantable tissue for people in desperate need and that iso-lating ES cells entails the destruction of embryos. It is less

widely known that ES cells also could be crucially in-volved in the creation of embryos; ES cells could ultimate-ly be used to create healthy children, andat least in prin-cipleto create genetically enhanced children.

ES cells have three remarkable properties. The first istheir pluripotentialitytheir capacity to be coaxed to de-velop into many tissue types. The second is their immor-talitytheir capacity to proliferate indefinitely in an un-differentiated form. Because of their immortality, if a re-searcher wanted to insert genes into cells, ES cell lines pro-vide an unlimited supply of targets.81 Finally, ES cells areextraordinarily malleable; that is, it is easier to insertgenes where you want them in ES cells than in other kindsof cells.82 The combination of their immortality and mal-leability not only makes ES cells superb targets for gene in-sertions but also makes them excellent vehicles for pro-ducing inheritable genetic modifications.83

If researchers were to perform gene transfer on ES cellsand then employed cloning to transfer an ES cells nucleus

into an egg, they could move from creating transplantabletissue to creating altered embryos (see figure 1). Those al-terations could be aimed at producing healthy embryosor enhanced embryos. In this respect, then, ES cell re-search is part of the bigger reprogenetic picture.

In 1998, when James Thomson and his colleagues iso-lated human ES cells, President Clinton asked the Nation-al Bioethics Advisory Commisison to provide advice re-garding ES cell research. NBAC delivered a report in latesummer of 1999. Given the medical promise of the re-search, NBAC argued, an exception should be made to thestatutory ban on federal funding of embryo research topermit federal agencies to fund research involving the de-

rivation of human ES cells.84 Thus a second high-levelgovernment panel followed HERP in arguing that someembryo research ought to be publicly funded.

Clinton rejected his own ethics advisory commissionsadvice, however, opting instead to accept the legal opinionof the Department of Health and Human Services gener-al counsel, Harriet Rabb, that the Dickey-Wicker amend-ment applies to research on embryosand that ES cells arenot embryos.85 Dickey-Wicker also states that federalfunds may not be used for research in which a humanembryo or embryos are destroyed, and ES cell research

entails the destruction of embryos. But Rabb opined thatthe letter of the law permitted federally-funded researchersto useES cells as long as they did not derivethem. Deriva-tion could be left to researchers in the private sector. In

August of 2001 George W. Bush employed the same use-derivation distinction but stipulated that federally fundedresearchers could use only ES cells that had been derived

with private money before 9 August 2001.86By relying on the use-derivation distinction, the Clin-

ton and Bush administrations squandered an opportunityto make a distinction instead between acceptable and un-acceptable purposes for embryo research. Everyone whohas used IVF has been the beneficiary of one sort of em-bryo research. And if anyone ever benefits from the ES cellresearch that the federal government now funds, that per-son will be the beneficiary of another form of embryo re-search.

If we want to enjoy such benefits, we should forth-rightly support continued embryo research. In giving oursupport we must recognize that the embryo research en-

terprise, which requires a destruction of human embryos,does entail a moral costas do many things we desire.Many would allow, for example, that slaughtering animalsfor food and allowing medical students to dissect cadavershave their costs, even though they are justifiable. In think-ing about embryo research, we must work out how we canboth respect embryos and, under some circumstances andfor some purposes, benefit from the things we can do withthem. We need to figure out the difference between thepurposes of the embryo research we want to endorse andthe purposes of that we reject. Hiding behind distinctionslike the one between use and derivation makes no sense

for those who wish to face the bigger reprogenetic picturein all of its complexity.The basic point here is that ES cells in particular, and

embryos in general, can be put to many different purpos-es. Adequate responses to those purposes will require morethan the blanket yes of the advocates or the blanket no ofthe critics. To their credit, some people in the anti-abor-tion camp have already, in light of the therapeutic possi-bilities opened up by ES cell research, begun to modulatetheir blanket no to embryo research. Senator Hatch, whois opposed to abortion, has stated that ES cell research is aform of embryo research he can support, and he supportsa bill that would permit the use of embryos in therapeutic

cloning research. As anti-abortion advocate Tony Blankley wrote in the Washington Times, The imminent privatesector exploitation of [ES cell research] will force intellec-tually honest right-to-lifers to abandon our cherished illu-sion of moral clarity on this issue.87 Similarly, pro-choicesupporters like George Annas and Lori Andrews have sug-gested that there ought to be limits on what we can withembryos.88

These are perhaps but preliminary calls for compro-mise, and they might prove ephemeral. If they are to leadto any genuine accord, with substantive consequences for



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promoting some forms of research and constraining oth-ers, they must receive some institutional support. We mustcreate a governmental body that will, among other things,facilitate systematic and nuanced policy deliberation aboutthe wide variety of health and non-heath-related things wecan do with embryos.

The Role of Government in Reprogenetics

There will be little disagreement about the claim thatsafety concerns warrant government oversight. Manypeople from within infertility medicine believe that weneed improved government oversight to protect partici-pants/consumers. 89 Many of those same people wouldprobably also agree that there ought to be some form ofpublic discussion about how this new research and prac-tice will affect the well-being of us all.

Two objections, however, can be raised against at-tempting to promote broad-based public deliberationabout questions of well-being and against attempting,

through political and moral deliberation, to develop acommon framework of values within which public policyon reprogenetics could be formulated.90 First, questionsabout possible future consequences are necessarily basedon claims that are more tentative than the scientificknowledge and empirical data that policymakers often

wish to have on hand before making decisions. But in fact,making public policy decisions under conditions of uncer-tainty and incomplete knowledge is a familiar problem,and the remedy is not policy inaction. What are requiredare open and reasonable deliberation, a sense of humilityin the face of very complex questions, a willingness to lis-ten and learn, and the flexibility and honesty to make cor-

rections to policy when initial assumptions or beliefs turnout to be mistaken.Second, some have argued that public deliberation and

public policy should be limited to procedural and techni-cal questions. This is primarily because, they believe,opening the public sphere up to issues as difficult and con-troversial as what constitutes human well-being would bedangerous in a pluralistic democracy. 91 It would be dan-gerous partly because it would be a source of conflict, andpartly because policies or laws informed by a particularconception of human well-being could threaten the liber-ty of those who hold different beliefs about human well-being.

This second viewpoint is important as a caution againstthe possible misuse of public deliberation, but it does notprovide a compelling reason to forgo the process of delib-eration altogether. Even in so contentious and sensitive anarea as human reproduction and family life, public policycannot and should not be limited to procedural issuesalone. Doing so suggests that all human relationships arecharacterized only by rational, voluntary contract and self-interested exchange. In this realm, public policy cannotand should not be limited to the negative, protective func-

tions of providing for individual security and the preven-tion of harm, as important as these are. The function ofpublic policy even in a democratic, pluralistic society isalso positive; it is to promote the enjoyment of liberty andrights, to promote social justice, and to promote the well-being of its citizens.

Liberty itself is an aspect of human well-being. Liberty

and autonomy cannot flourish in a society in which theindividual is merely protected from harm; they can flour-ish only where the individual also is supported in herhuman dignity and worthwhere she is educated and isprovided with equal opportunities to develop personal tal-ents and abilities. It would be supremely ironic if, out ofconcern for the protection of individual liberty and diver-sity of opinion, we hobbled the primary democratic vehi-cle we have that creates a context within which liberty it-self can prosper and be most meaningful. That vehicle isthe process of fair and open public deliberation about theconditions of justice and liberty in our polity, and the con-ditions of human well-being in our society. Contrasting

visions of human well-being are the lifeblood of politicsand are always at work, even though sometimes they are soself-evident to so many that we do not notice them atall. We should not fear this aspect of political discourseand deliberation, we should embrace it and put it to gooduse.

One of the governments responsibilities is to promotethe public welfare, and how reprogenetic technologies aredeveloped and disseminated will affect the public welfare.Some of those effects will be relatively narrow: amongthese more contained consequences might be legal dilem-mas regarding the identities of children and responsibili-ties of parents; questions regarding the care and support of

children, and issues surrounding the medical treatmentdecisions of children produced by these new techniques.92

Other effects will be broader: reprogenetics might trans-form the meaning of having a child, being a member of afamily, and being a member of a community.

Our government has an interest in influencing the de-velopment and dissemination of technologies with thiskind of power. Given that the current system of reproge-netics oversight is potentially dangerous, out of step withthe reality of the convergence of reproductive and geneticmedicine, and sometimes subverts genuine public conver-sation, it is time to contemplate new reprogenetic policymechanisms. It is, of course, ambitious to try to describemechanisms that are less dangerous, that reflect currenttechnological developments, and are capable of facilitatinga conversation about the bigger picture. Such a task couldnot possibly be accomplished in one fell swoop by any sin-gle group. We are at the beginning of a long process, andthis report merely points in one direction we might go tocreate safer and better-informed oversight of reprogeneticresearch and practice.



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here are several possible regulatory vehi-cles that might allow for better oversightof reprogenetics, and each strategy hasstrengths and weaknesses. The overarch-

ing recommendation of this report is for comprehensiveregulation of reprogenetic techniques in both the privateand public sphere. That recommendation is guided, inpart, by an analysis of the regulatory strategies of othercountries, in particular those of the United Kingdom andCanada. In spite of the close cultural ties between thosecountries and our own, differences in culture and politi-cal tradition make wholesale importation of either of theirregulatory schemes both impossible and inappropriate.Nonetheless, it is informative to consider what in thesecountries has worked and what has failed.

The United Kingdom

In 1984, the Committee of Inquiry into Human Fertili-sation and Embryology headed by Dame Mary Warnock (the Warnock Committee) issued a detailedreport outlining the results of a two-year consultationprocess on embryo research and assisted human reproduc-tion.93 The Warnock Report reviewed the ethical issues as-

sociated with new reproductive techniques and stated thecommittees opinions (both majority and minority opin-ions, in some cases) about what policymakers ought toadopt in designing oversight.

The Warnock Report covered many issues, includingsome controversial topics that generated significant dis-agreement, such as the moral status of the human embryoand the acceptability of human embryo research. Ulti-mately, the report articulated a number of opinions aboutthe acceptability of human embryo research, the need forlimits and restrictions to certain practices, and the need fora centralized oversight body that could create and imple-ment public policy and adapt to technological develop-

ments.The government adopted the recommendations of the

Warnock Report and drafted legislation aimed at regulat-ing the storage and use of gametes and embryos in treat-ment and research. The legislation, the Human Fertilisa-tion and Embryology Act 1990 established a nationaloversight body called the Human Fertilisation and Em-bryology Authority (HFEA).94 The HFEA has the statusof a quangoa body in an arms-length relationship tothe government that is housed outside the Department ofHealth yet is accountable to the Secretary of State. To en-

sure that it is not overloaded by scientist and clinicianvoices, the act stipulates that membership is interdiscipli-nary.

The HFEA is responsible, through various committees,for licensing and monitoring clinics and laboratories in-volved in gamete or embryo storage, creation, or use, andthe act sets out the purposes for which licenses will be re-quired (falling under the rubric of licenses for treatment,storage, or research).95 In addition, the HFEA functions asan information resource for patients, clinics, and cliniciansalike. It achieves this, in part, by establishing and publish-ing a code of practice giving guidance about the properconduct of activities carried on in pursuance of a licenseunder the Act. Through the setting of standards and theprovision of licenses, the HFEA provides both qualitycontrol and assurances that ethical conduct in embryo re-search is maintained.

The act also details the situations in which consentsmust be obtained.96 Through a series of detailed andmandatory consent procedures, it attempts to ensure thatpatients consider some later contingencies and how they

would respond to them. Should the couple divorce, for ex-ample, to whom do stored IVF embryos resolve? Conse-quently, in the face of disagreements and unforeseen cir-cumstances, the parties involved will have already articu-

lated their wishes with respect to dispositional authority,discard, or storage of their gametes or embryos, and un-necessary litigation can be avoided. Not all contingenciescan be foreseen, of course, but the system has proven quiteeffective.

Since research, storage, and treatment involving ga-metes and embryos are to be monitored, committees ofthe HFEA have been formed to approve protocols that usegametes and embryos in research and medicine. Conse-quently, the HFEA has responsibility for licensing novelapplications with embryos and gametes and, therefore,fulfills a policymaking function. When a novel applicationthat raises questions of well-being comes before a commit-

tee, the protocol is sent to the full HFEA for discussionand approval. Thus the smaller licensing committee doesnot make policy decisions that should be subject to broad-er discussion and approval. Finally, in addition to its li-censing and monitoring functions, the HFEA maintainsan information registry on the gametes, embryos, patients,and children that have been involved in licensed activi-ties.97

The authority of the HFEA to grant licenses is limitedby the purposes described in the act.98 The decision to ar-ticulate the purposes of embryo usage rather than specific


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techniques has ensured that the act can incorporate noveltechniques that were not envisaged when the act wasdrafted. In addition, if new techniques and applicationsemerge that fall outside the HFEAs statutory authority,the act allows parliament to expand the range of purposesthat are placed under the HFEAs authority, thereby en-suring that new purposes do not call for new oversight

agencies and preserving the integrity of the system. Theact has been drafted in sufficiently general terms, however,that it remains almost unchanged more than a decade afterits inception.

One reprogenetic development that the act could notincorporate, as initially written, was the isolation of EScells. The response was a good, if not painless, example of

well-informed democratic policymaking in the face ofrapid scientific advance.99 The government spearheaded apublic and policy debate about whether and when ES cellresearch and cloning techniques are valuable enough to bepermitted for some purposes, and about what those pur-poses might be.100 Both the HFEA (together with theHuman Genetics Advisory Commission) and an indepen-dent expert group formulated policy recommendations.101

The independent expert group recommended that EScell research be allowed for specific therapeutic purposesand that cloning techniques be permitted for the creationof research embryos that might lead ultimately to autolo-gous transplantation techniques.102 In addition, thegroups report (known as the Donaldson Report) recom-mended that future review of approved ES cell protocolsbe conducted to determine whether the research hasproven fruitful and merits continued use of human em-bryos. The Donaldson report was accepted in its entirety

by the government, which drafted additional purposes toadd to the Act by way of regulation. These amendmentswere accepted in a free (non-partisan) vote by parliamen-tarians.103 Consequently, these new reprogenetic tech-niques now fall under the oversight of the HFEA, main-taining a comprehensive, coherent oversight of reproduc-tive genetics.

The HFEA has been a model law for many countriesattempting to craft regulation in this area, includingCanada, Australia, and France. It is important to note,however, that the United Kingdom is not mired in a divi-sive abortion debate, and that fact probably helps explainthe public acceptance (for the most part104) of the over-

sight systems decisions.The support in the United Kingdom for the HFEA ex-

tends to the scientific and regulatory communities, whichappear to have worked out a nonadversarial relationship.

When a clinic cannot be licensed due to insufficiencies inits standards or its protocols, the HFEA works with thatclinic to ensure that it understands what is required for itto successfully apply for a license. Despite the comprehen-sive and highly centralized regulation, the United King-dom remains committed to scientific freedom, and ar-

guably has one of the most liberal embryo research policiesin the world.

There are a number of lessons to be gleaned from theexperience in the United Kingdom. First, recommenda-tions for Congress should be framed in general terms out-lining suggested restrictions, conditions, and limits on theuse, storage, and creation of embryos and gametes. Sec-

ond, acceptable and unacceptable purposes of embryo re-search should be articulated rather than specific tech-niques. Third, a mechanism for adding to or adapting theenabling legislation in the face of new developments or in-formation should be incorporated into the legislation.Fourth, a detailed informed consent procedure should beconsidered as a way of preventing unnecessary litigationand respecting patient autonomy. Fifth, the oversight au-thority should be responsible for developing a code ofpractice as a means of educating researchers, clinicians,and patients. And, finally, the respect the HFEA enjoys ispartly the result of its ability to make scientifically in-formed and coherent decisions. This ability derives fromits members considerable expertise and the wide discre-tion accorded them. Similarly, any U.S. oversight authori-ty will possess an expertise not likely shared by the mem-bers of Congress and should be granted significant discre-tion in making its decisions.

Canada

The Canadian policy experience in overseeing humanreprogenetic technologies has followed a slightlymore tortured path than the British. Its different experi-ence is partly the result of Canadas diversity of opinions

about reprogenetics, the depth and effort put into thepublic consultation process, and the constitutional andpolitical division of powers between the federal andprovincial governments.

In 1989, a Royal Commission on New ReproductiveTechnologies was established by the Federal Governmentto consult the public on issues related to new reproduc-tive technologies. The commission was charged with de-veloping a substantive analysis of the technologies impli-cations for Canadian citizens and society, and with mak-ing recommendations to the government for public over-sight. Over 40,000 Canadians were directly involved inthe commissions public consultation process.105

In 1993, the commission released its findings in a two-volume report, with fifteen volumes of supporting mater-ial and discussion.106 The report articulated an ethic ofcare that should govern this area of research and practiceand eight detailed principles that informed its recommen-dations. The commission made specific recommendations

with respect to prohibitions and restrictions that shouldapply to embryo research. In addition, it recommendedthe establishment of a national regulatory body responsi-ble for mandatory licensing of treatment and research in-volving gametes and embryos. Like the HFEA, the com-



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mission recommended that the regulatory body be at armslength from the government. In addition, the body was tobe constituted with a membership of at least 50 percent

women.These recommendations were followed three years later

by a voluntary moratorium on nine unacceptable prac-tices,107 which was widely regarded as unsuccessful. In

1997, a first legislative bill was introduced into parliamentas an attempt to act on the commissions recommenda-tions. That bill, Bill C-47 (the Reproductive and GeneticTechnologies Act) sought to criminalize a number of ac-tivities already subject to the voluntary moratorium andcame under intense criticism for its failure to establish a li-censing scheme or national regulatory body. 108 The billdied when an election was called in 1997. In May 2002,after extensive consultations with the provinces, a secondbillthis time entitled the Assisted Human Reproduction

Act (the AHRA)was introduced to parliament.109 Thatbill has now had received its second reading and is work-ing through the various governmental stages of legislativepassage. Like its predecessor bill, it has been the subject ofcriticism for its heavy reliance on prohibitions and crimi-nal sanctions.

Like the counterpart British act, the AHRA purports togovern the creation, use, and storage of embryos and ga-metes in both treatment and research. However, unlike theBritish act, it also bans commercial transactions in humanreproductive tissues (sperm and eggs) and commercial sur-rogacy. One of the guiding principles of the AHRA is theprohibition of commercial exploitation of human repro-duction. Interestingly, the AHRA enshrines the guidingprinciples of the act within the act itself rather than in a

preamble, as is more common.110

Placing the principleswithin the preamble means that they are not strictly en-forceable as part of the act and can be used primarily toclarify or interpret the meaning of the act. But if the prin-ciples are affirmed in the AHRA itself, theymustbe taken

into account when interpreting or implementing a sectionof the act or its supplementing regulations.

Also like the British act, the AHRA outlines the restric-tions, conditions, and prohibitions on uses of gametes andembryos. Both Canada and the United Kingdom haveprohibited modifying the human germline, sex selectionfor other than medical reasons, and creating human-non-

human chimeras. It is worth noting that all these activitieshave taken place or been attempted in the United States inthe absence of legal prohibitions and comprehensive over-sight.

The AHRA follows the British lead in establishing anational oversight body that has an arms length relation-ship to the government. The Assisted Human Reproduc-tion Agency is responsible for licensing and monitoring fa-cilities and for maintaining an information registry.111 Inaddition, it must communicate and consult with the pub-lic and set conditions to maintain a license under the act.The Canadian act, again like the British act, explicitly re-quires the oversight body to carry out a public consulta-tion and information function, aimed not only at the laypublic, but also at stakeholders such as clinicians and pa-tients. Clearly, the blueprint for the Canadian AssistedHuman Reproduction Act was the Human Fertilisationand Embryology Act 1990.

There are lessons to be learned from both the Britishand Canadian experiences, not the least of which is thatthe road toward coherent oversight is long and often tor-tuous. But the public conversation that forms the bedrockof that process is rich, informative, and important for in-dividuals and society alike. The ability to oversee reproge-netic research and practice from a national perspective

provides both scientific quality control and greater cer-tainty that ethically unacceptable activities are not beingconducted with gametes and embryos behind a veil of se-crecy in the private sector.



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here are many obstacles to any serious po-litical initiative to regulate reprogeneticsresearchand human embryo research ingeneral. Surely one of the greatest obsta-

cles is the fear each side in the abortion war will have oflosing any ground. Many people would prefer the statusquo to any risk of a setback.

But some people have begun to take such risks. And ifour society is to submit reprogenetic innovations to publicoversight, others must take such risks as well. Develop-ments in, for example, preimplantation genetic diagnosis,ooplasm transfer, cloning, and ES cell research invite us tostep back and contemplate the bigger reprogenetic picture.Thoughtful people should accept that invitation andbegin to think broadly and boldly: they should design asystem that can foster the discussion of safety and well-being concernsand can ensure that new reprogenetictechniques that raise those concerns do not slip throughthe regulatory cracks.

First Steps toward Public Discussion

We make three recommendations.

n First, to bring embryo research into the light of public

deliberation, Congress should lift the current ban on fed-erally funded embryo research. We cannot have responsi-ble oversight of reprogenetics research and practice, nor ofembryo research generally, if we do not first acknowledgethat we already support those activities in a wide variety of

ways. Our country has already embarked upon one bigembryo experiment. If we do not forthrightly accept thatfact by allowing the federal government to oversee researchand practice involving embryos, then the market will bethe only mechanism that will distinguish between the ac-ceptable and unacceptable purposes of those activities.

n Second, to take action toward regulatory oversight in

the United States, a commission must consolidate andtranslate the many documents that have already been writ-ten on this topic, solicit views from the diverse U.S. con-stituencies that are or should be engaged with this topic,and synthesize this material to make legislative recommen-dations about statutory authority for an oversight body.The work of the commission, referred to in this report asthe Reprogenetics Technologies Advisory Commission(RTAC), would be similar in some respects to that of theRoyal Commission in Canada, although the audience forthis body would be Congress. The advisory commission

would, in part, engage the public, stakeholder, and expertconstituencies in consultation; articulate the ethical com-mitments that must guide such a regulatory effort; anddraft the terms of reference for embryo research, includingthe limits, restrictions, and prohibitions to be written intolegislation. That commission would then report its find-ings in the form of recommendations to Congress for alegislative initiative.

n Third, in formulating its recommendations, the com-mission should carefully consider the possibility of creat-ing a standing federal entity, a Reprogenetics TechnologiesBoard (RTB), to facilitate reasoned and systematic publicand policy deliberation about the purposes of reprogenet-ic research and practice. The boards authority would ex-tend to the public and private sectors, and it would factorconcerns about safety and well-being into policy-makingand license-granting decisions. The board would, in im-portant respects, resemble the United Kingdoms HumanFertilisation and Embryology Authority (HFEA).

Drawing from the lessons learned in the United King-dom and Canadian experience, it will be important, first,that the Reprogenetics Technologies Advisory Commis-sions recommendations for Congress be framed in gener-

al terms; it should only outline its suggested restrictions,conditions, and limits on the use, storage, and creation ofembryos and gametes. Second, in defining the Reproge-netics Technologies Boards purview, the recommenda-tions (and the eventual legislation) should articulate ac-ceptable and unacceptable purposes of embryo researchrather than specific techniques. Third, recognizing that itis impossible to keep pace with scientific and technologi-cal developments, the legislative initiative should incorpo-rate a mechanism for adding to or adapting the enablinglegislation in the face of new developments or informa-tion. Fourth, the RTB should be granted significant dis-cretion, since its members will need to develop an exper-

tise not likely shared by the members of Congress. Fifth, adetailed informed consent procedure should be consideredto enable patients to contemplate what they want done

with their embryos and gametes in unexpected circum-stances like death and divorce; such procedures would beaimed both at preventing unnecessary litigation and re-specting patient autonomy. And, finally, the RTB shouldbe responsible for developing a code of practice as a meansof educating researchers, clinicians, and patients.

There are many possible obstacles to the creation of anew federal oversight board for reprogenetics. First, there


P A R T F I V E

A Policy Proposal

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is an open question about the constitutionality of any fed-eral regulation of scientific research that occurs in the pri-vate sector. To date, there is no clear indication that Con-gress cannot implement such regulation; indeed, that itcan has already been assumed in the bill recently passed bythe House to ban all cloning. Yet the possibility remainsthat the federal oversight board envisioned here would

face a constitutional challenge.Second, the recommendations will likely face opposi-

tion from the entrenched participants in the abortion de-bate. The recommendation to lift the embryo research ban

will raise deep concerns among anti-abortion advocates,who are likely to argue, starting from the premise that em-bryos are persons, that all embryo research is immoral andthat none should be publicly funded. And at least initially,the prospect of any mechanism to oversee reprogeneticsresearch and practice will raise deep concerns among pro-choice advocates, who may argue that accepting limits onthe things researchers and clinicians can do with embryosis the first step down a slippery slope to limiting a womansright to choose. Yet some people committed to the anti-abortion position now acknowledge that embryos in petridishes are not persons, and agree that there are somethings researchers ought to be permitted to do with em-bryos. Similarly, some committed to the pro-choice posi-tion now acknowledge that procreative liberty is not ab-solute, and agree that there are some things researchersand practitioners ought not to be permitted to do withembryos.

If any of these recommendations are to be taken seri-ously, then certainly, both sides of the abortion battle willhave to believe that their concerns will be taken seriously.

Thus if the advisory commission were to be appointed(much less if it were to recommend the creation of astanding board along the lines of the HFEA), then mod-erate representatives from all sides would have to be in-volved. Members of the commission would have to be ap-pointed by a bipartisan committee, with representationfrom both the House, the Senate, and a variety of stake-holders. Possibly the former chair of the National Bioeth-ics Advisory Commission and the current chair of thePresidents Commission on Bioethics could jointly help tonominate members.

Ongoing Discussion and Oversight

Even though the notion of creating an HFEA-like bodyin the United States will encounter resistance,112 thetime may be right. Others before us have called for regula-tory action on some of the topics touched on in this re-port. These proposals have often focused on reproductivemedicine, however, missing some of the larger concerns ofreprogenetics, and they have typically sought mechanismsto ensure the safety of participants, neglecting well-beingconcerns.

For example, in 1996 the now-defunct National Advi-sory Board on Ethics in Reproduction (NABER) recom-mended that serious and timely consideration be given inthe United States to the establishment of a standing feder-al regulatory body to license infertility centers. This body

would have responsibility and sufficient support for sur-veillance of infertility centers around the country for the

purpose of regulating and accrediting the provision of ser-vices of assisted reproduction.113 In a 1996 editorial inFertility and Sterility, Howard Jones, founder of the JonesInstitute of Reproductive Medicine (in Norfolk, Virginia),endorsed NABERs recommendation and claimed that it

was also supported by the American Society for Repro-ductive Medicine (ASRM) and the Society for AssistedReproductive Technology (SART).114 Jones cited a No-vember 1995 news release issued jointly by ASRM andSART, which states that [s]uch an independent licensingauthority might oversee and validate the clinical and labo-ratory practice of ART, and function independent of andbe funded separately from The American Society for Re-productive Medicine and The Society for Assisted Repro-ductive Technology.115 The consumer advocacy groupRESOLVE also endorsed the idea.116

Thus there appears to be some support in the provider-consumer community for the idea of a licensing authorityto improve safety, efficiency, and accountability in repro-ductive medicine. A number of groups have also called forbetter oversight in reprogenetics. A working group con-vened by the American Association for the Advancementof Science117 called for a body to consider not only thesafety but also the well-being issues raised by attempts to

reprogenetics and public policy: reflections and recommendations

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