JOURNAL OF WOMEN’S HEALTH & GENDER-BASED MEDICINEVolume 10, Number 6, 2001Mary Ann Liebert, Inc.

Ethical Issues in Fetal Surgery Involving a Twin Pregnancy

JOHN J. PARIS, S.J., Ph.D.,1 and MARY CATHERINE HARRIS, M.D.2

The dilemma of subjecting healthy persons to risk and possible harm through elective surgical procedures ofno benefit to them was highlighted in the mid-1950s when the first twin transplants were performed at the Pe-ter Bent Brigham Hospital. The healthy, immunologically identical twin was considered a possible kidney donorfor his or her twin with kidney failure. The hospital was concerned about the legal issue of assult and batteryinvolved in operating on a healthy person, and there were medical and psychological risks involved also. Theserisks included the hazards of surgery and anesthesia, the potential that the immunologically identical personmight develop the same disease that affected the sick twin and because of decreased renal function caused bythe loss of the donated kidney have greater morbidity, and the psychological stress both of uncertainty aboutbeing a donor and of guilt if aware of the need for the donation and unwillingness to donate.Over the decades since the twin transplants, there have been remarkable advances in pediatric and obstetri-

cal surgery that have made it possible to operate on a fetus in utero. These advances have been accompaniedby a number of medical and ethical dilemmas. Early on when procedures are untested, they fall in the researcharena, and they raise other unique moral questions: the moral status of the fetus, the use of minors as researchsubjects, and substituted judgment. The use of fetal surgery on one fetus of a multiple gestation raises addi-tional and very thorny questions. Although there may be benefit for the compromised fetus, there is significantrisk to other fetus(es) and to the mother. Fetal surgery comes with even more hazards than prenatal testing,which can cause abortion or premature labor.Since the Nuremberg trials after World War II and the Nazi concentration camp experiments, there have

been increasing numbers of codes and regulations about research using vulnerable populations, such as chil-dren, incompetent people, and prisoners. Federal regulations about the use of children in research specify thatexperiments with no direct benefit for the children as subjects should not be conducted using government fundsand set a standard for other nonfederally funded research.The authors have delineated carefully the issues of maternal-fetal surgery in women with a twin pregnancy and

the relevant legal and moral implications. The analysis of nontherapeutic research, hazards of prematurity associ-ated with multiple pregnancies, and relevant issues in medical ethics provide a paradigm for other similar moraldilemmas.John J. Paris, S.J., is Michael P. Walsh Professor of Bioethics at Boston College, Clinical Professor of Fam-

ily Medicine and Community Health at Tufts Medical School, and Adjunct Professor of Medicine at the Uni-versity of Massachusetts Medical School. Father Paris was a consultant to the President’s Commission for theStudy of Ethics in Medicine, the United States Senate Committee on Aging, and the Congressional Office ofTechnology Assessment. Father Paris has served as a consultant and expert witness in many of the landmarkbiomedical legal cases, such as those of Karen Ann Quinlan, Paul Brophy, Baby K, and Gilgunn. He is an

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Choices: Biomedical Ethics and Women’s Health

1Department of Theology, Boston College, and Department of Family Medicine and Community Health, Tufts Uni-versity School of Medicine, Boston, Massachusetts.

2Department of Pediatrics, Division of Neonatology, The Children’s Hospital of Philadelphia, University of Penn-sylvania School of Medicine, Philadelphia, Pennsylvania.

INTRODUCTION

SOME 40 YEARS AFTER THE FIRST in utero diagno-sis was performed, the issues involving in

utero interventions remain vexing. Among theunresolved problems are when and on whom toattempt fetal surgery. The thrust of the techno-logical imperative, which propels us into doingsomething simply because the technology isavailable, is compounded when coupled with therule of rescue that demands we attempt to saveevery imperiled life.1 When these forces are ap-plied to trying to save the life of a seriously com-promised fetus, the allure of attempting correc-tions in utero is great. Yet as fetal surgery pioneerMichael Harrison warns, failure to exercise cau-tion with regard to fetal interventions can lead todisaster.2

“What is the benefit,” he asks, “if a complex inutero procedure of an otherwise doomed fetusleads not to recovery, but to a ‘half-save’ of a lifeof intensive care?”2 Further, as Harrison notes,the ethical and policy concerns in such surgeryinvolve more than the interests of a compromisedfetus. In his sensitive phrasing, “Enthusiasm forfetal intervention must be tempered by reverencefor the interests of the mother and her family.”2

That concern for and protection of the interestsof others has, until now, been restricted to a cal-culus of the risks to the mother and the compro-mised fetus. Although anxiety, desperation, orguilt might influence or even sway the mother’s

choices, in our society the decision about whetheror not to attempt the surgery is almost always ex-clusively “the prerogative of the mother.”3 Wepresent a new challenge that expands the moralcomplexity of decision making involving fetalsurgery: interventions in a twin or multifetalpregnancy. There, the lives of the sibling fetusesas well as those of the compromised fetus andmother are placed at risk.

RISKS OF MULTIPLE PREGNANCY

Multiple pregnancy itself presents added risk.The primary hazard is premature birth, with itsassociated increase in perinatal mortality andmorbidity. The presence of an anomaly in one ofthe fetuses multiplies that risk. Alexander et al.4

report increased incidence of preterm labor intwin pregnancies in which one twin has a majoranomaly. Their data suggest that a twin preg-nancy complicated by a fetus with a major anom-aly will be delivered an average 2 weeks earlierthan a twin pregnancy without fetal anomalities.That earlier delivery will have the expected prob-lems of prematurity, including greater need formechanical ventilation, infection, and a longerhospitalization for the unaffected twin.

Although fetuses with a major anomaly have asignificantly higher perinatal mortality rate (278in 1000) than those who incur only a minor ab-normality (10 in 1000 to 56 in 1000) or those who

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incisive, critical analyst of issues in law, medicine, and ethics and their interface. His writings appear in awide range of medical and lay publications. He is the Ethics Section Editor of The Journal of Perinatology.Mary Catherine Harris is Associate Professor of Pediatrics, Division of Neonatology, University of Penn-

sylvania School of Medicine. After graduating from Vassar College as chemistry major with a secondary con-centration in music theory and voice, she earned her M.D. at Dartmouth Medical School and then completeda pediatric residency at Children’s Medical Center, Boston, and a fellowship in Neonatal Perinatal Medicineat the University of Pennsylvania. Dr. Harris’s research interests include neonatal infectious disease/im-munology, ethics, and residency education.

–Nancy Boucot Cummings, M.D., Series Editor

ABSTRACT

In utero surgery may provide benefit to a compromised fetus. The possibility of fetal surgeryin a twin pregnancy extends the risk-benefit calculus beyond that of the fetus and mother toinclude the companion fetus and raises the issue of when, if ever, may fetus B be placed atsubstantial risk to benefit fetus A. Insight into the ethical dimensions of this issue is pro-vided by the norms that govern the use of children in nontherapeutic research and the justi-fications used in twin-to-twin transplant cases.

are born of a normal twin gestation, it is of notethat Alexander et al. find that the normal twin in such cases has “an outcome similar to that ofthe central group” of a noncompromised twinpregnancy.4

The intrusion of fetal surgery dramatically ex-acerbates the risk to the healthy twin. The surgeryitself invariably precipitates a preterm delivery.Preterm labor is, in the words of Adzick et al.,“The ‘Achilles heel’ of fetal surgery.”5 The ad-verse impact of the early delivery is so great thatit threatens to undermine, and in many cases ren-ders nugatory, the technological advances pro-vided by the fetal surgery.

What is the scope of uncontrolled prematurelabor? Adzick et al. report that in their series ofin utero surgery for diaphragmatic hernia, “All ofthe patients delivered prematurely, usually 3 to4 weeks after the in utero procedure.”5 In the in-terventions to correct meningomyelocele in utero,virtually all the women delivered prematurely.6–8

Although prematurity associated with fetalsurgery might be an acceptable risk for a single-ton gestation facing a near certain demise, a sim-ilar risk of premature delivery imposed on a nor-mal twin fetus poses, as Harrison et al. put it inanother in utero context, “the serious ethicaldilemma of when to perform such procedures inhumans and how to obtain realistic consent.”9

We pose the question of open in utero surgeryin a twin pregnancy to raise the issue of what de-gree of risk a normal fetus should be exposed tofor the benefit of a compromised companion fe-tus. What is the moral basis for subjecting ahealthy fetus to a procedure that offers no thera-peutic benefit and, in fact, exposes it to signifi-cant risk? Who provides the proxy consent for thenormal fetus to enter into this nontherapeutic re-search? A background for understanding thesequestions can be found in two historical prece-dents: the use of children as research subjects andthe use of minors (or incompetents) for identicaltwin-to-twin kidney transplants.

A premise to this discussion is that for policypurposes the moral standing of a fetus beingbrought to term for delivery is that of a child.10

This, as Chervenak and McCullough11 note, is notto be understood in terms of independent moralstatus of the fetus, that is, some feature(s) of thefetus that, independently of other entities, in-cluding the pregnant woman, physician, and thestate, generates obligations of other to it. Rather,as they put it, the moral status of the fetus as pa-tient forms when “reliable links exist between it

and its later achievement of moral status as achild and then a person.”11 The two inexorablelinks here are the decision of the pregnant womanto continue a previable pregnancy to viability andthen to term and the presentation of the fetus toa physician for treatment. That is, the necessarynexus for the shift from fetus to patient is thepregnant woman’s decision not to terminate thepregnancy but to present the fetus (and herself)to the physician for the maternal-fetal surgerythat offers an expectation of benefit to the fetus.Once this is done, as Adzick and Harrison phraseit, “The fetus is now a patient.”12 Thus, the fe-tus—and any other fetus affected by that inter-vention—now occupies the same role as that ofany other patient in the physician-patient rela-tionship, one to whom the physician owes a dutyto “do no harm.”

NONTHERAPEUTIC RESEARCH ON CHILDREN

The history of research on children, as Glantz’sstudy13 of the topic establishes, has not alwaysbeen benign. From Jenner’s testing in 1802 of a vaccine (one he had developed and used on hisown 1-year-old son) on 48 children living in analmshouse and then exposing them to smallpoxthrough the now infamous hepatitis experimentson the mentally retarded at Willowbrook in the1970s, we have witnessed the willingness of zeal-ous researchers to subject children to experimentsnot to benefit the patient but to advance the skillsof medicine. Out of these experiences of abuseand exploitation—and that of the horrors of ex-perimentation in Nazi Germany—came the de-mand for rules governing research activity in-volving humans.

From the Nuremberg Code,14 with its empha-sis on “the voluntary consent of human subjects,”through the Federal Regulation on Protection ofHuman Subjects,15 the emphasis has been thatparticipation in nontherapeutic research must begoverned by informed consent. Further, as thecurrent federal regulations on participation ofchildren in research stipulate, even when there issome direct benefit to the child, these experimentsought not involve more than minimal risk. Thisemphasis on the protection of the patient followsKant’s categorical imperative that one must al-ways treat an individual as an end and not as ameans to some other goal.16 It is the dignity ofbeing a human that confers this status of auton-

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omy and self-determination on the individual.That autonomy, which precludes subordinatingthe interest of one human being to that of anotherwithout the subject’s voluntary consent, was firstrecognized in the legal literature in a 1767 Eng-lish case, Slater v. Baker and Stapleton.17 There, theHigh Court ruled that a surgeon could not test anexperimental device to repair broken bones on apatient without the patient’s knowledge and con-sent.

Application of that protection to research in-volving children is first found in the medical lit-erature in 1941, when Francis Payton Rouse, theeditor of the Journal of Experimental Medicine, re-jected a manuscript from a physician and wroteto the author: “The inoculation of a 12 month oldinfant with herpes . . . was an abuse of power, aninfringement of the rights of an individual, andnot excusable because the illness which followedhad implications for science.”18 Further, he added,“The statement that the child was ‘offered as a vol-unteer’—whatever that may mean—does not pal-liate the action.”18 That comment, as Glantz ob-serves,13 is an important turning point in thediscussion of research with children because it isone of the first statements to acknowledge thatchildren themselves have rights. The child is seenno longer as merely an extension of the parent butas an entity in his own right who has claim to themoral protection of the community.

If there are to be developments in remedies forchildhood diseases, research must involve chil-dren. Extensive debate over when and underwhat conditions that research should be con-ducted occurred in the 1970s in the now wellknown debates between Paul Ramsey andRichard McCormick on the ethics of nonthera-peutic research on children.19,20 For Ramsey, theissue was clear. Since children by definition wereincompetent to consent, they could not partici-pate in research unless the experimentation wasdirectly for their benefit. In his forceful phrasing,“Never subject children to unknown possiblehazards of medical investigation having no rela-tion to their own treatment.”20 McCormick tookissue with what he perceived as an overly rigidposition that would preclude children as a classfrom benefiting from medical advances. Chil-dren, he noted, are not simply “little people”pharmacologically. Hence, if there is to be devel-opment in pediatric medicine, experimentationinvolving children is, in his words, “absolutelyessential.”21

At this point, as McCormick notes, “a severeproblem arises.” The Nuremberg Code and theDeclaration of Helsinki22 seemingly preclude theuse of children from all nonbeneficial research.To get beyond that position, McCormick holdsthat a more fundamental moral analysis of hu-man nature reveals a social solidarity in the hu-man community such that if one, with minimalrisk to self, could contribute to the well-being ofanother, one ought to do that. Consequently, heargues that proxy consent for a child to enter intoan experimentation that does not put the child atgreat risk and offers benefit to another may le-gitimately be given by a parent.

That proxy consent, McCormick observes, isnot derived from a cost-benefit analysis. Such aprocess, which weighs the potential benefit to oneagainst the harm to another is, for him, an illicitutilitarianism. Rather, he holds that proxy con-sent is founded in “what all of us, as members ofthe community, necessarily ought to do. Thereforeit is what the child if competent would want todo.”21

McCormick’s position is that the consent givenis not charity, utilitarianism, or a work ofsupererogation. Rather, it pertains to the area ofsocial justice. It is, in McCormick’s words, “One’spersonal bearing of his share of the burden thatall may flourish and prosper.”21 Even for the pro-ponents of involvement of children in research,however, there is a limit to one’s social responsi-bility for the good of other members of the com-munity. The stopping point or the place at whichthe legitimacy of “constructed” consent for chil-dren to participate in research ends, McCormickargues, is “when the experiments involve de-scribable risk, undue discomfort, or inconve-nience.”21 If such real danger exists, what the in-fant is construed as desiring because he ought tois modified. No one ought to want what puts himin danger. Thus, one cannot legitimately postu-late consent for another where there exists sub-stantial danger, risk, or harm.

TWIN-TO-TWIN TRANSPLANTATION CASES

The notion of one person enduring harm tohelp another, as Francis Moore23 observes, prob-ably had its inception with cesarean section. Withthe advent of blood transfusions in World War I,that notion of placing one individual at risk to aid

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another became widely and socially accepted.Transfusion, as Moore shrewdly notes, was not abenign procedure in those days. With the firstidentical twin-to-twin kidney transplant at thePeter Bent Brigham Hospital in 1954, the extentof damage of one person to benefit another—and,more particularly, of one child to benefit a sib-ling—was radically increased. As minors or men-tally retarded young adults were involved inthese early twin-to-twin kidney transplants, thesurgeons sought legal guidance on who, if any-one, could give consent to place one child at riskto benefit another.

In a series of cases beginning in 1957 with Mad-sen v. Harrison,24 various courts have attemptedto set out standards for such action. That firstcase, which occurred in Massachusetts, involveda proposed transplantation between 19-year-oldtwins named Leonard and Leon. Since at the timethe age of majority was 21, Leonard could notgive legal consent for the transplant to his twinLeon. A Massachusetts Superior court judge, act-ing as a court of equity, authorized the transplanton the grounds of best interests of the donorbrother. In the judge’s words:

I am satisfied from the testimony of the psychi-atrist that grave emotional impact would be vis-ited on Leonard if the defendants refuse to per-form this operation and Leon should die, asapparently he will. . . .

I therefore find that this operation is necessaryfor the continued good health and future well be-ing of Leonard and that in performing the oper-ation the defendants are conferring a benefit onLeonard as well as Leon.

Subsequent courts followed this best interestanalysis to justify twin-to-twin transplants.

The most extensive articulation of the argu-ment is found in Hart v. Brown,25 a 1972 case inwhich a Superior Court judge in Connecticut au-thorized the transplantation of a kidney from thedonor to his identical 7-year-old twin. Using asubstituted judgment standard formulated in an1816 English case, Ex parte Whitbread,26 the Con-necticut court reasoned that it, like the Englishcourt, “could don the mental mantle” of the nowincompetent and discern and decide what the in-competent would want done. In the transplanta-tion case, the court confronted what the judge de-scribed as “a balancing of the rights of the naturalparents and the rights of minor children—moredirectly the rights of the donor child.”25 The Con-

necticut court found that the donor child wouldagree to the kidney transplantation because thefollowing conditions prevailed:

� A kidney transplant is not experimental butrather medically accepted therapy.

� Saving the life of the stricken child would ben-efit the donor psychologically.

� The risks to the donor and donee are negligi-ble.

� Prognosis for both children is excellent.� There is favorable review by community rep-

resentatives.� There is supervision by a court of equity.

With this case, “best interests,” “minimal risk,”and court-supervised “informed consent” be-came the standards required for judicial autho-rization of twin-to-twin transplantation.

FEDERAL STANDARDS FOR MEDICAL RESEARCH

Best interest, minimal risk, and informed con-sent were subsequently adopted as required stan-dards in federal regulations designed to protecthuman subjects in U.S. medical research.27 Theconsent standard, which is derived from theNuremberg Code’s emphasis on voluntary par-ticipation in experimentation, is still the domi-nant feature of research protocols, as can be seenin former Secretary of Health and Human Ser-vices Donna Shalala’s recent essay on what mustbe done to protect the well-being of research sub-jects in clinical trials.28 Even when guided by theHippocratic tradition of beneficence toward thepatient, the research physician’s interest is thegoal of the research, not the patient. This inher-ent conflict of interest necessarily excludes the investigator from being the one to assess the patient’s concerns in nontherapeutic research.Further, as Evelyne Shuster observes, it meansthat “the medical investigators cannot set therules for the ethical conduct of research.”29

The danger of physicians misconstruing theirrole vis-à-vis the patient in research situations iscaptured in Jay Katz’s description of the responseof Western physicians to the Nuremberg Code:“It was a good code for barbarians but an un-necessary code for ordinary physicians.”30 Evenafter the experience of the Nuremberg trials, mostphysicians do not see themselves as threats to

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their patients’ well-being, nor do they perceive aneed to protect research subjects from their de-signs. As Secretary Shalala’s directive makesclear, the nonphysician community does not fullyshare that perspective.

The most recent systematic reflection on thetopic of human experimentation is the 1996 Re-port of the U.S. Advisory Committee on HumanRadiation Experiments.31 That Committee wasconvened in response to allegations of abuses ofhuman subjects in radiation research sponsoredby the federal government during the Cold War.The Advisory Committee, which defined itself as“in essence, a national ethics commission,” set outthe basic ethical principles it believes to be so fun-damental as to apply in all research situationsboth past and present. The Committee identifiedsix basic principles as particularly relevant to re-search on human subjects:

1. One ought not to treat people as mere meansto the end of others.

2. One ought not to deceive others.3. One ought not to inflict harm or risk of harm.4. One ought to provide welfare and prevent

harm.5. One ought to treat people fairly and with equal

respect.6. One ought to respect the self-determination of

others.

These norms, states the Advisory Commission,“are the principles of obligation telling us whatwe ought to do.”31

Using these criteria, the Presidential Commis-sion had its harshest criticism for those cases inwhich physicians used patients without their con-sent as subjects in research from which the pa-tients could not possibly benefit medically. In theAdvisory Commission’s strong words, “Just asphysicians had no moral license to determine an‘acceptable risk’ for healthy subjects without theirvoluntary consent, they had no moral license todo so in the case of patient-subjects who couldnot benefit from being in the research.”31

From its study of the historical precedents ofmedical research in the United States, the Advi-sory Commission concluded, “Because risks tosubjects cannot be offset by the possibility thatthey might benefit medically, nontherapeutic re-search that puts subjects at significant risk israrely justifiable.”31 This concern for the researchsubject, as the Commission put it, is not a matter

of altruism but of straightforward “justice” to-ward the potential research subjects.

CONCLUSION

None of the historical, psychological, judicial,or regulatory analysis provides support for a sur-gical procedure that puts one patient at seriousor substantial risk to aid another. Nor does it pro-vide any justification for proxy consent that putsone fetus at risk to benefit another. In the in uterocontext, there is no psychological bonding, nor isthere a sense of grief occasioned by the death ofa sibling. In sum, there is no foundation in anyof the historical precedents for putting one indi-vidual at risk to benefit another that would sanc-tion or permit placing twin fetus B at risk solelyto benfit twin A.

In a twin pregnancy where there is no per-ceived benefit to the healthy fetus when a surgi-cal procedure is undertaken on a compromisedfetus, such surgery ought not be done. None ofthe analysis that supported proxy consent intwin-to-twin transplants or involvement of chil-dren in nontherapeutic experimentation appliesto placing a healthy fetus at substantial risk tobenefit another fetus. Since one patient ought notbe abused or exploited simply because another isin need, unless the intervention itself offers po-tential benefit to both twins, there is no justifica-tion for the imposition of risk on a healthy fetus.

Even in instances where one person is willingto place herself at risk for another, for example,a mother for her fetus, there are limits on whatconstitutes an acceptable assumption of risk. TheAmerican Academy of Pediatrics’ position on theethical parameters in these situations is unam-biguous: Under circumstances where the risk tothe mother is high and the benefit to the fetus isremote, “Physicians may refuse to offer such anintervention despite a pregnant woman’s insis-tence that something be done.”32

The physician is even more ethically bound torefuse a mother’s demand to do something tobenefit an anomalous twin fetus if so doing placesthe otherwise healthy twin fetus at substantialrisk. The beneficent-based ethical obligations ofthe surgeon to the normal fetus and respect forthat healthy individual’s autonomy precludeputting it at risk for the benefit of another. Asstated earlier by Harrison, “Enthusiasm for fetalintervention must be tempered by reverence for

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the interests of the mother and her family.”2 Here,reverence for the healthy fetus compels the fetalsurgeon to refrain from interventions that wouldsubstantially jeopardize that fetus’s well-being.

An analysis of the ethics of fetal surgery in atwin pregnancy illustrates the increasing moralcomplexity occasioned by technological develop-ments in reproductive medicine and maternal-fetal surgery. It also makes even more imperativea cautious clinical application in the use of thesetechniques.

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Address reprint requests to:John J. Paris, S.J., Ph.D.

Boston CollegeDepartment of Theology

Chestnut Hill, MA 02467

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