Designing Babies: Human Research Issues

Author(s): Rebecca Dresser

Source: IRB: Ethics & Human Research, Vol. 26, No. 5 (Sep. - Oct., 2004), pp. 1-8
Published by: Hastings Center
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 SEPTEMBER-OCTOBER 2004 * VOLUME 26, NUMBER 5

IIR

Designing Babies:

HICS

Human Research Issues

HUMAN RESEARCH

Designing Babies: Human BY REBECCA DRESSER

Research Issues

uman genetic engineering

germline engineering. A program

by Rebecca Dresser 1

was one of the earliest

to develop safe and effective

bioethics topics to attract

germline alterations would include

INSIGHT:

widespread attention. During the

preliminary animal studies and lab-

1960's, scientists and scholars began

oratory work involving human

Commercial Tissue Repositories:

examining the possible benefits and

embryos that would not be trans-

HIPAA Raises Sponsors' Fears

harms that could come from

ferred for gestation. Eventually,

attempts at human genetic

by Michael D. Allen 9

however, specific alterations would

alteration.' Germline genetic alter-

have to be tested in human

ations attracted the most controver-

Quebec Physicians' Knowledge

embryos expected to become chil-

sy. Genetic alterations made in early-

and Opinions Regarding

dren. At this point, multiple

stage human embryos would be pres-

Substitute Consent for

human subjects issues would arise.

ent in the cells of children developing

Decisionally Incapacitated Older

What preclinical data would sup-

from such embryos, including the

Adults
ply an acceptable basis for initial

germ (sperm or egg) cells. As a

human studies? Would the exis-

result, this form of genetic alteration

by Gina Bravo, Marie-France Dubois, Mariane

tence of alternative interventions

Paquet, Fabienne Langlois, and Jean-Pierre could affect not only children devel-

diminish the ethical justification for

Bernier 1 2 oping from genetically modified

human testing? What would be

embryos, but their descendants, too.

appropriate disclosure and deci-

The long-running debate over

Correction and Clarification

sionmaking procedures in studies

the ethics of germline genetic alter-

by Paul S. Appelbaum, Charles W. Lidz, and

that could last for the direct sub-

ation has focused on the technolo-

Thomas Grisso 1 8

jects' lifetimes and could include

gy's broad social implications, such

their progeny, as well?

as potential effects on parent-child

THE PARTICIPANT:

Human trials would present sig-

relations, social inequalities, and

nificant ethical and practical prob-

the human gene pool.z These

Some Precision Would Be Helpful

lems. These problems are serious

broad implications are only part of

enough to call into question the

by Michael Hamilton 19 the story, however. Extensive

justification for embarking on a

human subjects research would be

program aimed at human germline

ANNOTATIONS 8 required to bring germline genetic

interventions. In this article, I sur-

alterations to the clinic. Yet the

vey the major human subjects

INSTRUCTIONS FOR AUTHORS 20.
ethics of conducting such research

issues that germline genetic modifi-

has received comparatively little

cation studies would present. I

attention.

begin by explaining why there is

Recent events highlight the need

renewed interest in this form of

to pay more attention to the

genetic alteration. Then I describe

A PUBLICATION OF
research ethics issues. In the past

specific issues that would arise in

THE HASTINGS
few years, some scientists and oth-

evaluating proposed human trials.

CENTER
ers have endorsed an accelerated

An inquiry into these issues reveals

program to develop human

weaknesses in the case for pursuing

human germline alteration. There

Rebecca Dresser, "Designing Babies: Human

is strong reason to doubt that risks

Research Issues," IRB: Ethics & Human Research

to subjects would be outweighed

z6 No. 5 (zoo4): 1-8.

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 by potential benefits of modifica- der. New approaches that incorpo- effective way to deliver desirable

tions to avoid genetic disease or genes to the later-born children who

rate homologous recombination,

enhance normal traits. An unfavor- embryonic stem cells, cloning, and would be direct subjects of research.

able harm-benefit ratio would also artificial chromosomes are expected But investigational genetic modifica-

lessen prospective parents' interest to expand investigators' abilities to tions aimed at assisting later-born

in trial enrollment, which could add, correct, and replace genes early individual subjects could produce

make it difficult to collect the data in an organism's development.6 genetic changes in their descendants,

necessary to determine safety and Responding to the achievements too, changes that could be beneficial

efficacy. I conclude that the ethical in basic research and the disappoint- or detrimental to those descendants.

and practical problems in conduct- ing outcomes in human studies In this article, I use the term preim-

ing human trials will impede efforts aimed at somatic cell genetic alter- plantation genetic modification

to develop this technology.3 ation, certain scientists and scholars (PGM) to refer to genetic modifica-

argue that genetic alteration in tions in early embryos that are per-

Origins of the Contemporary preimplantation embryos offers formed with the intent to affect a

Interest in Germline Alteration

great promise for improving human resulting child, but are also likely to

health and welfare. Alterations per- have germline effects. Preimplan-

O ne source of the renewed inter-

formed at such an early stage could tation genetic modifications belong

est in human germline alter-

target genetic diseases, such as to a larger category of interventions

ation is the lack of clear success in

Huntington disease and cystic fibro- the AAAS working group labeled

studies using other methods of

sis, and could also produce rare but inheritable genetic modifications.

genetic modification. Since 199o,

desirable characteristics, such as an The larger category includes somat-

hundreds of people have participat-

unusually strong resistance to HIV.7 ic-cell genetic alterations and other

ed in studies aimed at altering genes

By the late 199os, respected biolo- techniques that could change the

in their somatic (nonreproductive)

gists such as James Watson, Leroy genes individuals transmit to their

cells. Although commonly referred

Hood, and Mario Capecchi had offspring. Because the magnitude

to as gene "therapy," the therapeutic

become enthusiastic about the and probability of effects on subjects

benefits of this approach remain

potential benefits offered by this and offspring would be particularly

unproven. Researchers have encoun-

form of genetic modification.8 At a high in PGM, however, this research

tered numerous impediments to suc-

1998 conference, these scientists presents its own set of human sub-

cessful gene insertion, as well as

joined other participants in suggest- jects issues.

adverse effects of viral vectors used

ing that successful human germline Ideally, human PGM studies

to deliver genes to child and adult

modification could be achieved would evaluate a modification's

subjects.4

within a few decades. Conference potential impact not only on direct

At the same time, scientists have

sponsors called on the Food and subjects, but on subjects' descen-

achieved significant advances in

Drug Administration and the dants, as well. A commitment to

other kinds of genetic research. The

National Institutes of Health (NIH) evaluate potential effects on direct

Human Genome Project has gener-

Recombinant DNA Advisory subjects' descendants would add

ated a wealth of information about

Committee to begin preparations for complexity to the assessment of

human and animal genetics.

reviewing human trials.9 Around the study risks and potential benefits,

Scientists have sequenced human,

same time, the American Assoc- substantially lengthen the study peri-

mouse, and other species' genomes,

iation for the Advancement of od, and increase the number of sub-

which has led to a better under-

jects needed to complete the study.

Science (AAAS) convened a working
standing of the relationships

group to assess the scientific, moral, Another noteworthy feature of

between genes and diseases.s Over

and policy issues to be considered in early-phase PGM research is that it

twenty years of experience with

decisions about human germline and would expose vulnerable human

transgenic techniques has produced

other inheritable genetic modifica-

populations-fetuses and children-

an array of new animal models of

tions.'0 Neither group examined the to serious risks with a low probabil-

human disease, as well. To create

human research issues in detail, ity of direct health benefit. Neither

transgenic animals, investigators

however.
past research experiences nor exist-

inject DNA from one organism into

ing ethical analyses have produced

the fertilized eggs of another organ-

Challenging Features of Human consensus positions on the condi-

ism. Researchers using these tech-

Studies
tions necessary to justify this form

niques have corrected disorder-pro-

of human research."

ducing mutations in embryos, there- he scientists and others endors-

Two additional features would

by creating healthy animals whose ing germline alteration portray

add to the complexity of human

offspring are also free of the disor- embryo modification as the most

IRB: ETHICS & HUMAN RESEARCH

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IB

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 PGM research. First, PGM research expressed in a low percentage of the
tion of a genetic modification's

would involve the generation of initial generation of animals with

potential effect on embryonic, fetal,

extracorporeal embryos.
genetic alterations and further breed-
and later human development.'8

Investigators would thus have to ing is required to obtain animals

Guidance on the preclinical find-

consider issues related to control

with stable and properly functioning
ings that would be necessary to sup-

over disposition of embryos that had foreign genes.14

port initial PGM studies comes from

undergone investigational genetic

Excitement about the prospects
a report on in utero genetic modifi-

modification. As in the infertility for human PGM comes from those

cation by the NIH Recombinant

treatment setting, rules would be

who expect that novel techniques, as
DNA Advisory Committee. In that

needed to resolve disagreements over well as refinements of existing meth-

context, the Committee determined

whether embryos should be trans-

ods, will emerge. Most observers
that before proceeding with human

ferred for gestation, donated for lab- believe that safe and effective PGM
studies, investigators should submit

oratory study, or discarded. Second,

would require a method of correct-
animal data establishing that: 1) effi-

it would be scientifically desirable ing or replacing specific mutated

cient gene transfer had occurred; z)

for surviving direct subjects to be DNA sequences, rather than adding

new genes were properly function-

followed throughout their lives."1

foreign genes. Although gene correc-
ing; 3) there were no detrimental

These features would complicate tion and replacement techniques are

effects on development before or

efforts to design and conduct ethical

currently under laboratory study,
after birth; and 4) there were no sig-

PGM research in humans.

they remain highly experimental.'s
nificant risks of triggering infectious

Artificial chromosomes might offer a

disease, cancer, or various degenera-

Assessing and Balancing Potential

satisfactory means of gene delivery,
tive processes.'9 Similar demands

Harms and Benefits

but according to a leader in the field,
would be appropriate in response to

the technique remains unproven and

proposals to study PGM in humans.
a~n evaluation of potential harms

"very much in the realm of basic

For PGM proposals, investigators
1-kand benefits is crucial to decid-

gene therapy research."'6

should also be required to submit
ing whether it would be ethical to

Because genetic modifications

animal data showing an absence of
proceed with any proposed human

serious adverse effects in the direct

study. Risks to subjects must be min-
would occur at a very early point,

PGM could have a major impact on

subjects' descendants.
imized and the remaining unavoid-

the developing human organism.

able risks must be justified by poten-

V Alternatives. Alternatives to

Scientists believe that many human

tial benefits to subjects, if any, and

PGM would also affect the justifica-

genes are pleiotropic, which means

the value of the information the

tion for human research. To be justi-

that they affect more than one trait.

study is expected to yield.13

fied, PGM studies should present a

Altering a pleiotropic gene could

Applying these principles to propos-

balance of potential benefits and

have unintended effects on later-born

als for human PGM would require

harms comparable to that presented

children. Animal testing of genetic

close attention to four areas: 1) pre-

by available alternatives.zo Several

modification techniques would sup-

clinical data; 2) PGM alternatives; 3) established alternatives offer

ply data relevant to human safety

conditions to be targeted; and 4) prospective parents an opportunity

and efficacy and would offer a

study procedures.

to avoid having children with serious

means to reduce the risks such tech-

monogenic disorders. These alterna-

I Preclinical Data. Extensive

niques would present to humans.

tives include implantation of unaf-

preclinical data would be necessary

Animal studies would provide less

fected embryos following preimplan-

to support initial human PGM trials,

guidance on the effects of a specific

tation genetic diagnosis (PGD) and

data that do not now exist. Even the

genetic modification, however, for

pregnancy termination following

strongest enthusiasts agree that no

human development might not

prenatal diagnosis of an affected

existing method of altering genes in

mimic development in animal mod-

fetus. Although PGD is a relatively

embryos is sufficiently safe and effec-

els.'~7 Nonhuman primate studies

new procedure, in the future it is

tive to attempt in humans. Current

would be most helpful, but even

expected to supply a means of

approaches to creating transgenic

those studies would not furnish

detecting a wide range of genetic dis-

animals are risky and inefficient.

definitive information on physical

Due to insertional mutagenesis and eases in preimplantation embryos."

and mental effects in humans.

Through PGD and prenatal diag-

other iatrogenic damage, relatively

Laboratory studies of human

few animals survive to birth and nosis, the vast majority of couples

embryos and embryonic stem cells

carrying genes for monogenic disor-

many surviving animals have serious

could yield data bearing on human

ders can produce children free of the

developmental abnormalities.

safety and efficacy, yet those data,

disorders. Some couples have moral

Foreign DNA is appropriately

too, would give only a partial indica-

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Ui

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 objections to these techniques, but prospective parents to avoid having be unethical for investigators to per-

no one expects that PGM would children affected by monogenic dis- form modifications exposing

enable couples to have healthy chil- eases, some writers speculate that embryos expected to develop into

dren without the possibility of polygenic diseases, such as cancer healthy children to significant risk in

embryo discard or pregnancy termi- and heart disease, could become exchange for a possible physical or

nation. Because it is highly improba- PGM targets. And enthusiasts and mental enhancement. Also, in some

ble that PGM could be performed critics alike think that enhancement circumstances, PGD would offer a

properly in every case, embryos and of normal human traits, such as dis- safer method of reducing the risk of

fetuses would have to be tested after ease resistance or intelligence, could having a child affected by polygenic

PGM to determine whether the become the major objective of disease or increasing the chance of

intervention had been successful. human PGM research.24 But studies having a child with a desired trait.29

Thus, couples would still face choic- involving alterations of genes linked Because every new genetic alter-

es about whether to initiate or con- to polygenic conditions or normal ation would present the possibility of

tinue a pregnancy when tests sug- traits would be ethically questionable different consequences to the human

gested that the resulting child would for several reasons. organism, proposals to modify genes

be unhealthy.2" Diagnostic accuracy would be a associated with polygenic diseases or

Existing genetic testing methods central concern. For PGM studies to to enhance normal characteristics

are inadequate for one group of be defensible, genetic tests would should be evaluated in light of the

prospective parents seeking to avoid have to detect with high accuracy specific modification's risks and

passing monogenic diseases to their the relevant disease or trait in preim- potential benefits to subjects.

children. This group includes couples plantation embryos. Genotypes Because many genes appear to have

in which both members are homozy- would have to be highly correlated pleiotropic effects and polygenic con-

gous for a recessive genetic disorder with phenotypes and the potential ditions exhibit such high variability,

and those in which one member is for variable expression among indi- it might not be possible to perform

homozygous for a dominant disor- viduals with the same mutation or modifications that would yield con-

der. At the same time, however, cou- among individuals with different sistent and material positive effects

ples unable to avoid passing genetic mutations of the same gene would without creating undue risk.30

diseases to biological children have have to be considered.zs Prediction

* Study Procedures. The evalua-

several reproductive options. accuracy could be limited for many

tion of human PGM would present

Through the use of donor gametes, monogenic conditions, but polygenic

numerous challenges related to study

couples may have unaffected chil- disorders and characteristics would

procedures. Researchers would have

dren genetically related to one par- present even greater prediction diffi-

to devise methods to evaluate PGM

ent. Such couples may choose to culties. Factors such as gene-gene

effects both before and after a direct

adopt or to have an affected child interactions and environmental influ-

subject's birth. Assessing such effects

and seek therapy for the condition. ences have significant effects on how

would require examining preimplan-

In the future, improved therapies polygenic conditions are manifest-

tation embryos, pregnant women

might also be available for children ed.z6 Inaccuracies in predicting target

and fetuses, and surviving subjects

affected by genetic disease.23 The conditions would be an ethical prob-

throughout their lives. Some PGM

availability of prenatal testing, PGD, lem because PGM research risks

effects could be subtle or delayed;

donor gametes, adoption, and better would be unwarranted if an embryo

for example, genetic modifications

therapies for affected children would had a reasonable chance of develop-

might contribute to "non-gross

substantially limit the population of ing naturally into a healthy or mildly

changes in complex system develop-

affected child.
couples seeking investigational PGM

ment ... or ... late-life results of

to avoid having children with mono- Given PGM's likely risks and

inflammatory or degenerative com-

uncertainties, some have argued that

genic diseases. Potential benefits to a

plications."31 Because modifications

small group of prospective parents it would be justified solely for life-

could be inherited, subjects' children

dissatisfied with these options would

threatening or severely debilitating

should be followed, as well. Multi-

conditions that cannot be prevented

offer weak justification for exposing

generational monitoring would be

children to significant risks from or treated in other ways.27 Others

necessary to ascertain inheritability,

investigational PGM. contend that PGM studies aimed at

stability, and other PGM features

avoiding less serious disorders or

over time.
S Appropriate Target

enhancing human traits would offer

Conditions. Since the availability of Scientists and oversight groups

sufficient benefit to outweigh the

alternatives virtually eliminates the would have to establish appropriate

risks to subjects.28 Under existing

need for PGM as a means to allow tests and monitoring procedures for

research ethics principles, it would

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 each of these stages, as well as the
PGM would be acceptable if it were
research subjects from birth and

appropriate duration of follow-up.32

"no more risky than the normal
would later confront choices about

Monitoring approaches used to

process of birth and conception."36

whether to maintain their study par-

detect possible germline effects from

Another is that clinical availability
ticipation. As adults, direct subjects

somatic cell genetic interventions and

should be conditioned on "strongly of PGM would have to decide

infertility procedures could be useful

supported assurances that [PGM]
whether to cooperate with ongoing

in PGM studies, but new forms of

would create no short-term or long-
study requirements, including repro-

assessment would probably be need-

term deleterious physical conse-

ductive testing and follow-up, and

ed, too.33 For example, scientists

quences in the resulting children"
whether to allow their own children

currently lack information about

and that risks to descendants would to be followed.

conditions in the genetically modi-

be "no greater than their risk of
Human PGM trials would have

fied embryo that might signal health

being born with the genetic condi-

several features that could impede

problems for a later-born individual.

tion at issue."37 According to a third
data collection efforts. The concerns

One researcher noted, "the only way

more permissive position, PGM that
about risks and uncertain benefits

to measure an effect now, with our

led to the birth of children who
discussed above could make prospec-

present state of ignorance, is either

would otherwise not exist would be
tive parents reluctant to try investi-

to have a gross defect or death. We

acceptable as long as the children
gational PGM. The available alterna-

simply cannot know what the effect

were sufficiently healthy to have lives
tives to PGM and the demands that

is in the zygote when an exogenous

that were better than no life at all.38
trial participation would entail could

gene is injected, whether we 'see' any

Underlying these three standards are
make it difficult for researchers to

problems or not."34 The ideal

different judgments about the moral
enroll a sufficient number of subjects

human study could also last a very

significance of reproductive choice,
to evaluate PGM safety and efficacy.

long time. Indeed, "large numbers of

children's health and well-being, and

U Prospective Parents. Prospec-

individuals might have to be fol-

the responsibilities of parents and

tive parents deciding about PGM

lowed for such long periods of time

researchers. More thought would be

research ought to recognize the risks

that the originating investigators

needed to develop practical applica-

and significant uncertainties that

may no longer be alive."3s This need

tions of any of these standards; some

would accompany such research.

for long-term follow-up is not

degree of public and professional

They ought to have a reasonable

unprecedented in human research,

agreement on the underlying moral

understanding of existing data rele-

but PGM studies would present

issues would be necessary, as well.

vant to a proposed genetic modifica-

unusual follow-up demands because

tion, but they should also under-

of the probability of consequences to Subject Recruitment Issues

stand that neither preclinical data

subjects' offspring.

Ethical human research requires nor initial human findings could

Many of the above questions

the informed and voluntary con-

fully predict the modification's effect

would arise in the planning of safety

sent of adult participants. Research

on their child. Prospective parents

studies. Later-stage studies would

involving embryos and fetuses

ought to be prepared for the possi-

introduce additional complexities.

expected to become children requires

bility of embryo discard or pregnan-

Because other genes and environ-

the informed and voluntary consent

cy termination for problems detected

mental conditions often influence a

of prospective parents. Pediatric

prenatally. They ought to realize that

gene's effects on an individual, ran-

research requires both the informed

the investigational intervention could

domized controlled trials might be

and voluntary permission of parents

damage a future child's health or be

needed to evaluate whether certain

and the assent of sufficiently mature

ineffective in producing the desired

PGM interventions were effective in

child participants.39 Human PGM

correction. They ought to under-

making the desired correction.

studies would involve each of these

stand that a child could require

Although such trials could be diffi-

participant groups. Each group

treatment for an uncorrected genetic

cult to conduct, researchers would

would face decisions involving com-

condition or a problem caused by

have to collect outcome data from

plex facts and substantial uncertain-

the investigational intervention.40

scientifically rigorous studies to sup-

ties. Prospective parents would

They ought to recognize that study

port clinical applications of PGM.

encounter a series of choices about

participation could include extensive

Writers have proposed a variety

interventions affecting embryos and

follow-up obligations, including

of standards for determining when

fetuses. Parents would face decisions

autopsy if their child died.4~' Finally,

human study data would support

about whether to allow continued

they ought to be aware of the possi-

offering PGM interventions in the

monitoring of their genetically modi-

ble effects-negative or positive-

clinical setting. One position is that

fied children. Children would be

that genetic alterations could have

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 on their child's descendants. assent. Researchers would be obli- good chance that improved thera-

Because PGM would involve gated to discuss basic study infor- pies would become available.

extracorporeal embryos, research mation with children and to respect Investigational PGM could be a par-

planning would also have to address the children's wishes to the extent ticularly unappealing option for

embryo disposition. Couples under- customary in pediatric research. prospective parents hoping to

going in vitro fertilization ordinarily When direct subjects reached an enhance their children. For these

issue instructions governing embryo appropriate age, researchers would couples, the choice might be:

disposition if divorce, death, or have to tell them about PGM's "Would you opt for a traumatic ...

other unexpected events occur.42 potential health effects, including procedure that might give you a

This mechanism could be useful in the impact it could have on subjects' very slightly happier child, might

PGM research, as well. Prior offspring. When subjects reached give you a less happy, less talented

instructions would not completely adulthood, investigators would need child, might give you a deformed

resolve the embryo disposition ques- to secure their voluntary and child, and probably would do noth-

tion, however, for couples and informed consent to remain in the ing?"46

investigators might later disagree study. If the subjects had children, Successful PGM research would

over whether to implant or destroy the disclosure and discussion cycle also require retaining a sufficient

genetically modified embryos. For would begin again. number of direct subjects. Unless

example, after PGM occurred, Achieving informed and volun- future research produced PGM

embryo testing might signal health tary decisionmaking in PGM interventions with little apparent

problems for a future child. research would be challenging, to

risk and extraordinary effectiveness,

Investigators might advise against say the least. The peculiar circum- it could prove impossible to enroll

transferring the embryo to the stances characterizing PGM and retain a sufficient number of

woman's uterus for further develop- research would at minimum require

participants to acquire the data

ment, but the couple might prefer to supplementing the usual disclosure needed to evaluate PGM's safety

risk having an impaired child. and decisionmaking process. and efficacy in humans.

Investigators could refuse to carry Prospective parents and direct sub-

Conclusion
out the couple's wishes, but like any jects would require a "short course"

research participants, couples would on human genetics,45 and children

Studies of PGM would present

be free to discontinue study partici- would require explanations tailored

serious and complex human sub-

pation. Couples might then seek to to their intellectual abilities. To meet

jects issues. Both supporters and

have health professionals elsewhere participants' educational and psy-

critics have neglected this dimension

transfer the modified embryo for chological needs, long-term involve-

of PGM. Supporters stress the bene-

further development. Courts and ment of genetic counselors and

fits that successful PGM could deliv-

other authorities considering dis- mental health professionals inde-

er, while opponents fear that explicit

putes in the treatment context have pendent of the research team might

discussion of human research lends

generally assigned gamete-providers be required.

legitimacy to a technology that

control over embryo disposition.43 This detailed look at the deci-

would be unethical for reasons

Yet investigational PGM might war- sions that couples and direct sub-

other than safety concerns.47 Rather

rant limits on prospective parents' jects would confront suggests that

than paving the way for permissive

control over modified embryos if researchers could encounter serious

PGM research, however, close

testing suggested that later-born subject recruitment obstacles in

examination of the human subjects

children would have serious health attempting to obtain the data neces-

issues reveals that PGM studies

problems.44 sary to evaluate PGM. Because of

would pose numerous ethical and

the risks, uncertainty of benefits,

U Subjects with Genetic practical problems. These problems

and array of alternatives available

create serious doubts about the need

Modifications. After a genetically

to prospective parents, few might be

for and feasibility of a program to

modified child's birth, investigators

willing to enroll in PGM studies.

develop human PGM.48 Future dis-

would be engaged in ongoing dis-

Many couples seeking to avoid hav-

cussions should consider not only

cussions with parents about study

ing children with serious diseases

what might be wrong with creating

procedures and the child's health

could find donor gametes, adoption,

status. Researchers would have to designer babies, but also what

prenatal testing, or PGD and trans-

obtain the parents' agreement to might be wrong with investigating

fer of healthy embryos more accept-

whether they could be created.

continue with trial participation

able options. Other couples might

and, as the genetically modified

prefer to risk having an affected

child matured, obtain the child's

child, particularly if there were a

IRB: ETHICS & HUMAN RESEARCH

SEPTEMBER-OCTOBER 2004

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 AR, Frankel MS, eds. Designing Our
Acknowledgment 95; Stock G, Campbell J. Engineering the

human germline symposium: Summary report. Descendants: The Promise and Perils of

Thanks to George Annas, Jeff

June 1998. Available at:

Genetic Modification. Baltimore, MD: Johns

Botkin, Joel Frader, Mark Frankel, Jon http://www.ess.ucla.edu/huge/report.html, last Hopkins University Press, 2003, p. 93-101.

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9. See ref. 8, Stock and Campbell 1998, p. Inevitable Genetic Future. New York:

Ossorio for helpful discussion of the

3-4- Houghton Mifflin Company, oo2002; Frankel

ideas contained in the manuscript and

io. See ref. 6, Frankel and Chapman MS. Inheritable genetic modification and a

valuable comments on an earlier draft.

2-000.
brave new world: Did Huxley have it wrong?

11. Oberman M, Frader J. Dying children Hastings Center Report 2003;33(1):31-36.

Funding/Support: This research was

and medical research: Access to clinical trials. 25. Wenstrom KD. The correlation

supported by the National Institutes of

American Journal of Law & Medicine between genotype and phenotype. In:

Health/National Human Genome

Recombinant DNA Advisory Committee.

2003;29:301-317; Annas G. Baby Fae: The

Research Institute.
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and Ethical Issues. 2000, p. 81-88. Available

tation. Hastings Center Report 1985;15(:1):1-

N Rebecca Dresser, Ph.D, is Professor of Law at http://www4.od.nih.gov/oba/rac/gtpcre-

17.

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IRB: ETHICS & HUMAN RESEARCH SEPTEMBER-OCTOBER 2004

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All use subject to JSTOR Terms and Conditions
 40. See ref. 2, Resnik et al. 1999, p. 42.

ANNOTATIONS
41. King N. Accident and desire:

Inadvertent germline effects in clinical

research. Hastings Center Report

Kerr C, Robinson E, Stevens A, their levels of risk. All of the chair-

2oo003;33(z):23-30.

42. Robertson J. Precommitment strategies

Braunholtz D, Edwards S, Lilford R. persons approved non-therapeutic

for disposition of frozen embryos. Emory Law

Randomisation in trials: Do poten- studies on minors if the level of risk

Journal zool;50:989-1o46.

tial trial participants understand it was generally low. However, when

43. Coleman CH. Procreative liberty and

contemporaneous choice. Minnesota Law

and find it acceptable? Journal of
the apparent risk was clearly higher

Review 1999;84:55-127.
than minimal the researchers found
Medical Ethics zoo4;30(1):80-84. *

44. Similar conflicts between prospective

The authors explore whether lay wide variance in the decisions of

parents and researchers might arise about

adults can identify true methods of chairpersons. According to the

whether a genetically modified fetus should be

carried to term, but in this situation the preg-

randomized selection and if these authors, this finding suggests general

nant woman would have clear authority to

methods are believed to be fair when uncertainty about the standards of

make the decision.

used in clinical trials. Participants protection for minors involved in

45. See ref. 2, Walters and Palmer 1997, P.

were asked whether four types of research in Germany. They suggest

42.

selection (using a computer to sort greater ethical and legal regulation

46. See ref. 30, Pinker 2003.

47. Philipkoski, K. Time for a new pair of

names, tossing a coin, pulling names of non-therapeutic research with

genes? Wired News. November 27, 2ooz.

out of a hat, and asking people what minors and see the ratification of the

Available at

they prefer) were random or not ran- European Convention on Human

http://www.wired.com/news/print/o,1294,566

dom. They were then asked if those

o8,oo.html, last accessed July 15, 2oo004. Rights and Biomedicine as an impor-

48. For an argument that human PGM

tant step.
4 processes would be acceptable for

research should be assigned low priority

use in a clinical trial. Study partici-

because other research objectives offer more

pants correctly assessed computer, Ravelingien A, Mortier F, Mortier

significant benefits to humanity, see Dresser R.

Futile science? Designer babies as a research

coin toss, and names in a hat as ran- E, Kerremans I, Braeckman J.

aim. American Journal of Bioethics, forthcom-

Proceeding with clinical trials of ani-

dom. All three of those methods,

ing.

however, were deemed "unaccept- mal to human organ transplantation:

able" ways to assign people to a A way out of the dilemma. Journal

medical regimen in a clinical trial. A of Medical Ethics 2oo4;30(1):92-98.

large group identified "asking people * Ravelingien et al. discuss the safety

what they prefer" as non-random, and ethical issues of xenotransplan-

but as an acceptable technique in a tation in clinical trials. Barriers to a

clinical trial. The authors propose successful transplantation between

that their subjects understood the animals and humans continue to

term "random" but reject its use in exist, including immunological rejec-

medical trials. Future clinical trial tion and the transmission of diseases

participants will need a stronger jus- across species. The authors believe

tification for the scientific benefit of that overcoming these barriers can

randomization to fully accept its use. only be done within a clinical trial.

Given the many risks to living

Lenk C, Radenbach K, Dahl M, patients, the use of humans in a per-

Wiesemann C. Non-therapeutic manent vegetative state (PVS) is sug-

research with minors: How do chair- gested. The authors recommend that

persons of German research ethics living wills specify a person's own

committees decide? Journal of definition of death (thereby avoiding

the societal debate about when death

Medical Ethics 2004;30:85-87. *

Lenck et al. evaluate and discuss the occurs) and state their desire to be

decisions made by the chairpersons used for research upon reaching that

of German RECs in the difficult field state. Some concerns may arise

of non-therapeutic research with about family or societal respect for

minors. A questionnaire distributed

the bodily integrity of the deceased,

but the authors suggest that a clear

to 49 German REC chairpersons

described five different research sce-

living will overcomes those objec-

narios involving non-therapeutic tions by putting preference on an

individual's wishes.
research with minors and varying in

SEPTEMBER-OCTOBER 2004 IRB: ETHICS & HUMAN RESEARCH

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