Displaced Agendas: Current Regulatory
Strategies for Germline Gene Therapy
Emily Marden and Dorothy Nelkirr
targeted
technologies which
Recent developments in biotechnology are radi-
cally affecting the nature of reproduction and the man-
ner in which we approach disease. In particular, germ-
line gene therapy, or the insertion of genetic material
into cells while they are developing and dividing, offers
the promise of eradicating genetic defects in humans
during embryonic development
In this article, the
authors argue that the social and ethical implications of
the developments in the field of germline gene therapy
have not yet received adequate consideration. Unlike
previous
already-
developed cells, germline gene therapy can potentially
correct and eliminate genetic deficiencies at the devel-
opmental stages of a cell. This raises issues of genetic
enhancement beyond the therapeutic applications of
this technology. However, the authors submit that an
established pattern of subordinating social and ethical
issues to technical and scientific debate in the regula-
tory arena is repeating itself in the case of discussions
over germline gene therapy. The authors suggest that
the American scientific regulatory process fails to fully
meet the challenges of this technology, particularly be-
cause social and ethical issues are not formally consid-
ered in the existing process. They therefore suggest that
American regulatory agencies should look to the ap-
proach taken by Europe with regard to germlne gene
therapy as an emerging technology, and that it may be
necessary to incorporate effective public debate over
social and ethical concerns into a regulatory process
which is primarily concerned only with the efficacy of
new technologies.
Les d6veloppements r6cents en biotechnologie
ont un impact sdrieux sur la nature de la reproduction
ainsi que sur notre conception de Ia maladie. En parti-
culier, la thdrapie g~nique germinale, soit l’insertion de
matdriel g6ndtique dans des cellules en cours de d6ve-
loppement et de division, ouvre
la perspective
d’6liminer les anomalies g6ntiques chez les 6tres hu-
mains an cours du d6veloppement embryonnaire. Les
auteures soutiennent que les questions sociales et 6thi-
ques soulevdes par les progri~s dans ce domaine n’ont
pas encore 6t6 assujetties ii une analyse ad6quate. Con-
trairement A la technologie pr~adable ciblant des cellu-
les d~j& developpdes, la th~rapie gdnique germinale
peut potentiellement corriger et 6liminer des d6ficien-
ces gntiques lors du d6veloppement d’une cellule.
Ceci soul~ve, au-delk des applications thdrapeutiques de
cette technologie, la problmatique de l’am6lioration
gdnetique. Malgr6 cela, il apparalt que la tendance A
subordonner les considerations sociales et dthiques au
debat scientifique et technique dans le contexte de la r&
glementation se manifeste lors des discussions portant
sur la thdrapie gdnique germinale.
technologie,
Les auteures avancent que le processus am6ricain
de riglementation scientifique ne rpond pas aux defis
posds par cette
surtout parce que
l’approche existante ne tient pas formellement compte
des questions sociales et dthiques. Elles suggirent par
consdquent que les agences am6ricaines de rdglemen-
tation se toument vers l’approche adopt6e par l’Europe,
qui, traitant la thdrapie gdnique germinale comme tne
technologie nouvelle, reconnalt qu’il peut s’avdrer nd-
cessaire d’incorporer un ddbat public efficace sur les
inquidtudes sociales et 6thiques au sein d’un processus
de rdglementation qui, autrement, se pr6occupe avant
tout de l’efficacit6 des nouvelles technologies.
. Emily Marden is an Associate at Sidley and Austin in Washington D.C. practising in the area of
Food and Drug Law. Dorothy Nelkin holds a University Professorship at New York University
teaching in the Department of Sociology and School of Law. The authors wish to acknowledge the
extraordinary help of Dr. Philip Noguchi and of Shana Strom.
McGill Law Journal 2000
Revue de droit de McGil 2000
To be cited as: (2000) 45 McGill L.J 461
Mode de rdfdrence : (2000) 42 R.D. McGill 461
MCGILL LAW JOURNAL / REVUE DE DROITDE MCGILL
[Vol. 45
Introduction
1. Germline Gene Therapy: The Potential for Permanent Change
II. The Interests Driving Germline Gene Therapy
A. Scientific Hubris
B. Commercial Interests
C. Media Hype
Ill. Social and Ethical Issues
IV. Existing Regulation is Not Adequate to the Challenges Posed by the
New Technology
A. FDA Review
B. NIH Review
C. European Policy
Conclusions
2000]
E. MARDEN AND D. NELKN – GERMLINE GENE THERAPY
463
Introduction
Scientific developments in the biotechnology age have introduced radical new
technologies that are changing the nature of birth and reproduction as well as the way
we approach disease. In recent years, these developments have included a variety of
new reproductive technologies, cloning techniques, transgenics, gene replacement
therapies, and hormonal manipulations. Proponents advocate these advances with
enthusiasm, promising everything from total reproductive control and freedom from
disease, to a higher state of human evolution. Others doubt the very wisdom of the
interventions and advocate the imposition of tight restrictions on the pace of change.
The social and ethical implications of these new technologies are profound. they not
only hold potential and poorly understood risks, but they also hold the power to radi-
cally alter the genetic and cellular structure of human beings. The latest technology,
and perhaps the most controversial, is germAine gene therapy.
Germline gene therapy involves the insertion of genetic material into cells while
they are still developing and dividing. The purpose is to replace faulty or missing
genes.’ The idea behind the therapy is to “fix” babies with genetic defects before they
complete their development.! A recent proposal, for example, would involve genetic
manipulation at the pre-implantation stage of embryonic development, the stage at
which the embryo consists of only four to eight cells Genetic manipulation at this
early stage is likely to affect most, if not all, of a developing foetus’ cells. Thus far, the
technology looks promising. Scientists involved in pursuing the technique point to
preliminary data from animal models which suggest that germline gene therapy will
be effective.’
The technology is far more radical and controversial than earlier gene therapy
protocols. Soiiatic cell gene therapy, the prevailing technique to date, aims to replace
flawed genes in already developed individuals and is targeted to particular classes of
cells. Under this technology there is negligible risk that germ cells will be affected
and that the trait will be passed on to progeny. However, in the case of germline ge-
‘See J.D. Watson et aL, Recombinant DNA, 2d ed. (New York: Scientific American, 1992) for ad-
vances in genetic research). See also Council for Responsible Genetics, “Position Paper on Human
Germ Line Manipulation” (Fall 1992) at 1-3 [unpublished, archived with authors].
2 “Genetics U.S. Experts Say Time to Think About Gene Therapy In Womb” Gene Therapy Weekly
(12 October 1998), online: WL (HTHNEWS) [hereinafter “Gene Therapy in Womb”].
3 For purposes of this article, the term “germline gene therapy” is used inclusively to refer to gene
therapy directed expressly at the germ cells and gene therapy directed at the pre-implantation embryo.
In directing gene therapy at the pre-implantation embryo, one has a theoretical opportunity to correct
a genetic defect (or enhance) and to affect the germline. Later interventions, such as in utero gene
therapy, also raise concerns about effects on the germline; however, in general in utero gene therapy
has no intent to alter germ cells. Nevertheless, recent in utero gene therapy proposals indicate the
movement toward earlier applications and raise concerns about germline effects.
4 See R. Kolberg, “RAC Tiptoes into New Territory: In Utero Gene Therapy” (1995) J. NIH Re-
search 37.
MCGILL LAW JOURNAL/ REVUE DE DROITlDE MCGILL
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netic manipulation, it is expected that the procedure will affect the foetus’ germ cells
Scientists could therefore potentially “correct” a genetic deficiency in every embryo,
thereby permanently eliminating the undesirable trait from future generations. At the
same time though, the transferred genes could cause deleterious mutations that could
also be passed on to progeny. Germline gene therapy offers a direct route to manipu-
lating genetic expression in human beings, which raises significant questions about
potential uses of the technique for the purposes of enhancement, well beyond any
therapeutic goals.
Typically, the regulation of a new science in the United States gives priority to
technical questions of risk and relegates social or ethical issues to subsidiary discus-
sions.’ This pattern is based on ingrained assumptions about scientific rationality and
the ability of technical experts to distance themselves from social or political influ-
ence. When recombinant DNA techniques were introduced in the early 1970s, for ex-
ample, initial public attention focused on the social, political and ethical ramifications
of the technology. However, scientists and regulators quickly redefined the debate in
terms of the safety and efficacy of the science.! Social considerations were gradually
marginalized and often ignored. Similarly, expert assessments of the safety of bovine
growth hormone were allowed to overwhelm the dissenting voices of farmers and so-
cial critics in the regulatory arena.’ Another example was in the dispute over foetal tis-
sue research, where researchers refocused the issue on the technical criteria which
determine the definition of life instead of giving way to an ethical debate over foetal
rights.”
A similar pattern is emerging in the case of research on germline gene therapy.
Though currently at an early stage of development, this clinical technology has been
the subject of debate among scientists and bioethicists for years. The concerns came
into sharper focus, however, in September, 1998, when geneticist W. French Ander-
son, an advocate of gene therapy, presented a “pre-protocol” for in utero gene therapy
to the National Institutes of Health (“NIH”) Recombinant DNA Advisory Committee
(“RAC”). At that time, it became clear that the research was moving quickly and in-
exorably toward actual clinical application. The subsequent response of the RAC sug-
gests that social and ethical concerns will once again occupy only a limited place in
regulatory discussions. The applicable regulatory agencies, the Food and Drug Ad-
ministration (“FDA”) and the NIH, are structured to focus on safety and efficacy
rather than on social or ethical implications. Moreover, the RAC’s role within the NIH
‘P.R. Billings & S.A. Newman, “Crossing the Germline” Genewatch 11:5-6 (January 1999) 1; Wat-
son, supra note I at 569.
6See generally D. Nelkin, ed., Controversy: The Politics of Technical Decisions (Beverly Hills: Sage
Publications, 1992).
‘S. Krimsky, GeneticAlchemy (Cambridge: MIT Press, 1992).
‘ See E. Marden, “Recombinant Bovine Growth Hormone and the Courts: In Search of Justice”
‘See S. Maynard-Moody, “The Fetal Research Dispute” in D. Nelkin, ed., supra note 6, 82.
(1998) 46 Drake L. Rev. 617.
2000]
E MARDEN AND D. NELKIN – GERMUNE GENE THERAPY
465
was recently reduced, its membership cut back, and its power diminished.” Ulti-
mately, in this regulatory environment, it is likely that ethical debates will be margi-
nalized as germline gene therapy proceeds toward application.
This pattern stands in striking contrast to proceedings in Europe on the same
subject. The Europeans have allowed social and ethical issues to set the agenda for
germline gene therapy. The Council of Europe decided that biotechnologies which
modify the genome of any descendant are an affront to “human dignity” and are
therefore socially and ethically unacceptable.” This decision effectively ‘banned
germline gene therapies in Europe based on social and ethical grounds alone.
This article examines the current regulatory regime with regard to the broad range
of issues raised by germline gene therapy. Part I describes the technique of germline
gene therapy and its current status. Part II reviews the convergence of scientific hu-
bris, commercial interests, and the media hype driving the technology. Part I looks at
the broad range of potential problems associated with the therapy. Finally, Part IV re-
views the existing regulatory apparatus, and notes its limited ability to deal with the
social and ethical issues that are bound to arise during clinical applications.
I. Germline Gene Therapy: The Potential for Permanent Change
The earliest gene therapy experiments, called somatic cell gene therapy, sought to
treat disease by altering genetic material in an individual’s affected cells.” These ex-
periments began in 1991 with great fanfare. However, technical problems in deliver-
ing genetic materials to diseased cells have thus far limited the success of these ex-
periments.” Germline gene therapy, on the other hand, aims to get around these prob-
‘” See “Recombinant DNA Research: Proposed Actions Under the Guidelines” 61 Fed. Reg.
59,726, 59,727-28 (1996) [hereinafter “Proposed Actions”]. For later implementation of these
changes, see “Recombinant DNA Research: Actions Under the Guidelines: Part II” 62 Fed. Reg.
59,032 (1997) [hereinafter “Actions Under the Guidelines”]. Some argued that the changes made to
the RAC would actually benefit public debate. For example, FDA believes that it was the case-by-case
review by the RAC that actually marginalized ethical discussion; FDA’s hope is that the new focussed
RAC will have more, rather than less, time for ethics.
” Council of Europe, Convention for the Protection of Human Rights and Dignity of the Human
Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and
Biomedicine, E.T.S. No. 164 (1997), online: Council of Europe
Biomedicine].
” See FDA, “Guidance for Human Somatic Cell Therapy and Gene Therapy” (Center for Biologics
Evaluation and Research, March 1998) at 3. For a description of somatic cell and germline gene ther-
apy, see generally, Watson, supra note 1.
‘” T. Friedman, “Human Gene Therapy” (1996) 2 Nature Medicine 144 at 145; N. Touchette, “Gene
Therapy: Not Ready for Prime Tune” (1996) 2 Nature Medicine 7 (“gene therapy, although having
great long-term prospects, has been oversold to the public”). Even W. French Anderson admitted the
ongoing lack of success with somatic cell gene therapy: see Engineering the Human Germline Sympo-
sium
the Human Germline Symposium
online: Engineering
(Summary Report)
(1998)
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lems by manipulating the “pre-implantation embryo:’ the stage at which an embryo
consists of between only four and eight undifferentiated cells. The genetic manipula-
tion is intended to replace defective genes at this very early phase, thus transmitting
healthy genes to every iteration of the dividing cells.” On the basis of animal studies,
scientists have already indicated that this form of gene therapy could be an effective
treatment for cystic fibrosis.” In 1998, a lobby of well known scientists including W.
French Anderson and James Watson, the Nobel prize laureate for the discovery of the
structure of DNA, publicly proposed extending genetic engineering techniques to the
germline.”
It was shortly after this announcement that Anderson presented research “pre-
protocols” to the NIH as a way, he claimed, to force a discussion of risks involved
with the procedure. Indeed, the question of regulation has moved to centre stage. An-
derson proposed to modify the genes of foetuses affected with adenosine deaminase
deficiency (‘ADA”)” and an inherited blood disorder, known as severe alpha thalas-
semia,” by introducing viral carriers carrying replacement ADA and protein genes
into the cells of an affected foetus.” Anderson made the proposal “with collaborators
from the University of Nevada, the Reno Veterans Affairs Medical Center, the Univer-
sity of Southern California, the National Institutes of Health and a private company
founded by Anderson, called Human Gene Therapy.” He claims that the technique
will be ready to perform within several years.’
Hunan Genntine].
” See E. Tanouye, “Efforts to Repair Fetal Genes Spark Debate Over Risks, Ethics” Wall Street
Journal (2 April 1996) BI.
” R. Kolberg, supra note 4. Scientific articles on germline gene therapy are a presence in the litera-
ture. See e.g. B. Gulbis et aL, “Protein and Enzyme Patterns in the Fluid Cavities of the First Trimes-
ter Gestational Sac: Relevance to the Absoptive Role of Secondary Yolk Sac” (1998) 4 Molec. Hum.
Reprod. 857.
“See Engineering the Hunan Germline, supra note 13.
,ADA
is an enzyme essential to the function of several cell types. In individuals with two dysfunc-
tional ADA genes, the foetal immune system does not develop. As a result, the affected newborn will
have a severe immune disorder and will thus be susceptible to infections and suffer high morbidity
and mortality rates.
“‘ Alpha thalassemia is a condition in which mature forms of hemoglobin are not properly pro-
duced, because a foetus lacks functioning alpha chain producing genes. As a result, the affected foe-
tus generally will die around 20 weeks of development.
” J. Couzin, “RAC Confronts In Utero Gene Therapy Proposals” (1998) 282 Science 27. See also
Billings & Newman, supra note 5.
P.R. Billings & S.A. Newman, supra note 5 at 1-3.
” See “Just In Case You Think We’re Making This Up”, online:
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E. MARDEN AND D. NELKIN – GERMLiNE GENE THERAPY
The NIH considered the pre-protocols in January 1999 and postponed approval in
view of the many questions that remain unanswered. However, given the confluence
of interests driving germline gene therapy, it may soon be a clinical reality.
II. The Interests Driving Germline Gene Therapy
As with so many areas of new technology, the progression toward germline gene
therapy is driven by the convergence of scientific hubris, commercial interests, and
media hype.’
A. Scientific Hubris
Many scientists and biomedical researchers herald the technology as a means of
eliminating dreaded genetic diseases such as cystic fibrosis and ADA from the popu-
lation. Together with patient advocates, they promise a day in which genetic disease
will no longer be a reality2 ‘ Dr. Anderson, who has been a passionate advocate of de-
veloping gene therapies, has claimed that the techniques will revolutionize the nature
of disease treatment, predicting that in the future, “[p]hysicians will simply treat pa-
tients by injecting a snippet of DNA and send them home cured.”‘
Other researchers have made equally hyperbolic promises about germline gene
therapy. In June 1998, a group of practitioners met at a one-day symposium spon-
sored by UCLA’s Science Technology and Society Program to foster public aware-
ness of the emerging technology. John Campbell, a UCLA geneticist and moderator
of the symposium, stated that
Germline engineering may enable us to obtain the benefits of a century of ge-
netic science. We now have the capacity to develop techniques to reliably and
accurately introduce DNA constructs into germ cells and could begin to con-
ceive and design genetic therapies to ward off diseases and improve the quality
of human life.2
James Watson spoke of the new technique with equal enthusiasm: “Germline therapy
will probably be much more successful than somatic [gene therapy]. We might as well
do what we finally can to take the threat of Alzheimer’s or breast cancer away from a
family.'” Lee Silver, a participant at the same symposium, similarly posited that “we
now have the power to seize control of our evolutionary destiny.”‘
‘ See RAC Statement (11 March 1999) online: Office of the Recombinant DNA Activities Home-
page
E. Maiden & D. Nelldn, “Cloning: A Business Without Regulation” (1999) 27 Hofstra L. Rev.
569.
24 W. French Anderson, summarized in Engineering the Human Germline, supra note 13.
,. Quoted in P. Dewitt, “The Genetic Revolution” Thne 143:3 (17 January 1994) 46.
26Engineering the Human Germline, supra note 13.
” Ibid. at9.
2Ibid at 19.
MCGILL LAW JOURNAL / REVUE DE DROIT DE MCGILL
[Vol. 45
Such statements reflect the belief that medicine must continually progress and
embrace new technologies. Bioethicists L. Munson and L.H. Davis support this im-
perative:
[Miedicine itself has a prima facie duty to pursue and employ germline gene
therapy … [We want to claim that members of the medical profession would
be collectively derelict if research aimed at the therapeutic use of germline
gene therapy were neglected without good reason.”
Similarly, ethicists John Fletcher and G. Richter claim that as the potential to diagnose
genetic diseases becomes increasingly feasible, “[tlo refuse to pursue forms of gene
therapy … would be morally self-defeating at this juncture of human genetics”
Proponents of germline therapy also tend to dismiss fears about the impact of the
technology on society. James Watson reflected:
I just can’t indicate how silly I think is [the sanctity of the human gene pool]. I
mean, sure, we have great respect for the human species. We like each other.
We’d like to be better, and we take great pleasure in great achievements by
other people. But evolution can be just damn cruel, and to say that we’ve got a
perfect genome and there’s some sanctity to it … [is] utter silliness.’
Lee Silver has also touted the economic and social efficiency of a society in which
there are “gen-rich” and “gen-poor” members. According to him, such genetic divi-
sions would result in more fulfilling and productive lives for all involved.’
B. Commercial Interests
Commercial interests have converged with scientific hubris in promoting germ-
line therapy. The economic stakes in this arena of technology are high. Currently, the
United States has approximately 1,300 biotechnology companies employing 140,000
people. The product sales of genetically engineered products in 1997, including drugs
and vaccines, were in the amount of $13 billion as compared to $7.7 billion in 1994,
and there are 200 new products in final-phase trials or awaiting FDA approval. The
total American investment in biotechnology R & D was approximately $9.1 billion in
1997.” Industry observers predict that the first gene therapy drug will be on the mar-
“R. Munson & L.H. Davis, “Germ-Line Gene Therapy and the Medical Imperative” (1992) 2
” J. Fletcher & G. Richter, “Human Fetal Gene Therapy: Moral and Ethical Questions” (1996) 7
Kennedy Instit. Ethics J. 137 at 153.
Hum. Gene Therapy 1605.
James Watson, quoted in Engineering the Human Germline, supra note 13.
“See “Just In Case You Think We’re Making This Up”, supra note 21 (quoting and analyzing Lee
M. Silver’s book Re-making Eden (New York. Bard, 1998)).
“) See MJ. Maiinowski & N. Littlefield, “Transformation of a Research Platform into Commercial
Products: The Impact of United States Federal Policy on Biotechnology” in T. Caufield & B. Wil-
liams-Jones, eds., The Commercialization of Genetic Research.- Ethical Legal and Policy Issues (New
York: Kluwer Academic/Plenum Publishers, 1999) 63. See also generally Pharmaceutical Manufac-
turers and Research Organization, PhRma 1998 Industry Profile’ online: PhRma Publications
2000]
E. MARDEN AND D. NELKIN – GERMuNE GENE THERAPY
ket by 2000 and that by 2005 gene-therapy sales are expected to amount to $3.5 bil-
lion.’
With the growing focus on gene therapy, research in the area has enjoyed signifi-
cant infusions of venture capital? Members of the media have noted that, “if this area
of science appears to be moving a bit fast for some members of the public, investors
might say it isn’t moving fast enough “‘ The driving motivation behind large com-
mercial investments for pharmaceutical companies rests in a desire for “know-how …
so we can translate discoveries in the field into a concrete therapy, which Sandoz and
Novartis would own and make money from””
Economically, genetic enhancement is one of the most promising areas of gene
therapy. Consumer demand for such therapies is already evident with the embrace of
human growth factor therapy to “treat” shortness.3″ It has been predicted that “the de-
mand for gene enhancement therapy will probably be very large, to give your children
a better chance of success in the world.”‘
C. Media Hype
The media has picked up and amplified scientific and financial hype over this
technology. When reporting on complex scientific issues, journalists often rely heav-
ily on press releases from scientists and biotechnology firms The result is often un-
bridled enthusiasm reflected in the headlines: “Genetic research leaves Doctors hope-
ful for Cures”, “New Hope for Victims of Disease”, “Genetics, the war on aging… [is]
1999).
3 J. Lanthier, “It’ll Take Longer to Clone Cash: Duplicating a Sheep Made Big Headlines But In-
vestors Seeking Returns from Genetics Must be Patient” Financial Post (29 November 1997) 8. An-
other report predicts that the market for gene therapy could reach $45 billion by 2010. See L.M.
Fisher, “Two Deals Extend the Financial Frontiers of Gene Therapy” The New York Tunes (10 January
1997) D5.
(date accessed: 3 December
Lanthier, ibid.
36Lanthier, ibiL
SE. Johnson, “Boehringer Networks to Get Ahead in Gene Therapy” (1997) 15 Nature Biotech.
12. See also L. Seachrist, “Bioethics Experts Sort Out Limits of Genetic Engineering” Bioworld To-
day (19 February 1998), online: WL (HTHNEWS) (“I don’t believe we would be having the debate
over genetic technologies if there weren’t money to be made”).
‘ See e.g. R.T. King Jr., “Study on Growth Hormone’s Benefit in Boosting Height May Prolong
Debate” Wall Street Journal (18 February 1999) B7; A. Toufexis, “A Growing Controversy: Debate
Over Using Human Growth Hormone Injections to Make Short Children Grow Taller” Tune 142:2
(12 July 1993) 49.
” Daniel Koshland, quoted in Engineering the Human Germline, supra note 13 at 10. See also
comments of Sheila M. Rothman, quoted in V. Kieman, “Cosmetic Uses of Genetic Engineering May
Soon Be A Reality” Chronicle of Higher Education 44:6 (3 October 1997) A18 (“People are eager to
use technology that they believe will improve their behavior, appearance or performance”).
4 See generally D. Nelkin, Selling Science: How the Press Covers Science and Technology (New
York: W.H. Freeman, 1995).
470
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[Vol. 45
the medical story of the century … Genetic technologies will dramatically curtail heart
disease, aging and much more”‘ A Gannett News Service story announced “Designer
Genes in Store: Manipulative Therapy Just a Decade Away” and went on to suggest
that “the ability to remove chance from our genetic hand of cards is closer than we
think ” ‘ A professor of bioethics is quoted in another story: “Gene therapy for im-
proving people is coming, and it will make it possible to improve your eyesight, your
sex life, your hairline and your disposition.”‘ An article in MSNBC On-line reported
that the technology could make real the “promise of being born cured:” The article
adds: “With gene therapy at the earliest stages, the likelihood of successfully rewriting
the genetic code in all the relevant cells is much greater .2′
Ill. Social and Ethical Issues
The development of germline gene therapy raises many questions about potential
risks and especially those risks which may be imposed on future generations. Some
critics, both scientists and bioethicists, express concern about the impact of germline
gene therapy on the human gene pool, noting that a systematic elimination of geno-
types may disrupt the delicate balance of dominant and recessive genes in the global
gene pool.’ They point to the fact that “bad” genes also serve useful purposes, noting
for example that the gene that causes sickle cell anemia also confers partial resistance
to malaria.” This begs the question: could genetic manipulations result in grave new
disorders or genetic incompatibilities?” In this vein, biotechnology critic John Fagan
has expressed that germline engineering “will progressively corrupt the blueprint of
our species with genetic errors.” Accordingly, these errors “will irreversibly burden
future generations with new genetic diseases, causing millions to suffer.”‘
‘ A. Rosenfeld, “The Medical Story of the Century” Longevity (May 1992) 42.
4T. Friend, “Designer Genes In Store, Manipulative Therapy Just a Decade Away” Florida Today
(4 November 1997), online WL (BUSNEWS).
” K. Danis, “Making Super Babies; Kids Bred to be Perfect May Lack Some of What Makes Us
Human” The New York Post (20 December 1998), online: WL (BUSNEWS).
“G. McGee, “Designer Babies Raise Tough Questions” (1999) online: MSNBC Home
“Ibid.
46 See D. Gianelli, “Fetal Gene Therapy Plan Stirs Fears Over Long-Term Safety” American Medi-
cal News (19 October 1998), online: WL (HTHNEWS) (“[Germine gene therapy] ‘may unintention-
ally disturb the finely tuned function of one or several genes. … interfere with the natural course of
human evolution and have unforeseeable consequences on the survival of the species’).
47 C. Joyce, “Should We ‘Fix’ Nature’s Genetic Mistakes?” USA Weekend (24 April 1998) online:
USA Weekend
(date
accessed: 17 March 2000).
” D.C. Wertz, “Germ-line Gene Therapy Enters the Foreseeable Future” The Gene Letter (August
1998) online: GeneLetter
” J.B. Fagan, quoted in Editorial, “Will Cloning Beget Disasters?” Wall Street Journal (2 May
1997) A14.
2000]
E. MARDEN AND D. NELKIN- GERMLINE GENE THERAPY
There is a similar concern that the ultimate safety of germline genetic manipula-
tions may be unknowable until many years after the treatment:
Even if successful germline gene therapy can be done, it is difficult to design
animal [models] that would predict potential late-stage complications in hu-
mans. For example, germ-line gene therapy might cure a patient of a fatal neu-
rologic disease, but 20 to 30 years later a severe disabling polyneuritis might
develop, one that did not occur in the preclinical toxicology tests.”
Scientist Dr. Gary Nabel has observed that correcting genetic flaws may carry
some unassessed risk: “You may have a method offering a cure for an inherited dis-
ease, but it carries with it a finite risk of acquiring cancer later in life. We have no way
of knowing … what the risk will be over a patient’s lifetime'”‘
These long-term risks impose ethical dilemmas. There is, for example, no way to
integrate informed consent into applications of germline gene therapy. Ethicist John
C. Fletcher has noted that those who would be most affected by germline gene ther-
apy, the foetus and its offspring, cannot adequately give consent. This would seem to
imply that the consent process must be refrained.
Others concerned with the ethical implications of the technology point out that
germline gene therapy could lead to dangerous eugenic practices.! If scientists are
able to replace a defective cystic fibrosis gene in a developing foetus, we would be
only one step away from replacing genes for physical and even character traits
deemed to be socially undesirable. Critics fear that this will result in a new, more in-
imical class structure, in which the rich can buy their way into biological superiority.”
A stunning example of this concern is illustrated by a recent report that an eleven
year-old boy was receiving gene therapy treatments at a cost of U.S. $150,000 per
year to increase his height. Four inches below average height, he was reportedly tired
of being teased for being short. His father was quoted as embracing this effort: “You
want to give your child that edge no matter what. I think you’d do anything”
T. Gregory, “Clinical Applications of Molecular Medicine” Patient Care 32:18 (15 November
1998) 86, online: WL (HTHNEWS).
5 Dr. Gary Nabel, quoted in R. Cooke, “Altering People: A Case of Ethics” New York Newsday (22
2 J.C. Fletcher, “Moral Problems and Ethical Issues in Prospective Human Gene Therapy” (1983)
November 1994) B30.
69 Va. L. Rev. 515 at 542-43.
” Historian Daniel J. Kevles has demonstrated that eugenic dreams often arise from seemingly
neutral medical capacities. See generally DJ. Kevles, In the Name of Eugenics (New York: Knopf,
1985).
P.R. Billings & S.A. Newman, supra note 5. For an in-depth look at the social problems raised by
enhancement therapy, see E. Patens, “Is Better Always GoodT’ (1998) 28:1 Hastings Center Report
SI.55Supra note 47.
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Bioethicist William Gardner’ has questioned whether genetic enhancement could
be controlled once introduced:
If genetic enhancement is feasible, it is likely that there wil be demand for it
because parents compete to produce able children and nations compete to ac-
cumulate human capital in skilled workers. If some parents or nations begin
using genetic enhancement this will change these competitions in ways that in-
crease the incentives for others to use it.
The Council for Responsible Genetics, a group comprised of geneticists and mo-
lecular biologists, issued a statement warning that germline gene therapy could easily
drift toward the creation of “designer babies”: “If this first proposal is accepted, how
much longer will it be before… any child who doesn’t measure up to some arbitrary
standard of health, behavior or physique is seen as flawed?”‘ This sentiment is ech-
oed by disability groups who fear that they will be devalued or be seen as having
“lives not worth living” if it were possible to eradicate their disability.”
Finally, critics claim that germline gene therapy represents an addiction to the no-
tion of progress. The technology, they note, is not really necessary given alternative
and available therapies. After all, the goal of eliminating diseased foetuses can be ac-
complished by prenatal diagnosis and selective abortion, or pre-implantation diagno-
sis and selective discard of affected embryos, without the added costs or moral quan-
daries involved in germline gene therapy.’ As one scientist has concluded, ‘The sim-
pler and safer technique of pre-implantation genetic diagnosis, already in clinical use,
renders germline gene therapy for genetic diseases virtually pointless'”‘
Dr. Paul Billings, chief medical officer of the Department of Veterans Affairs in
Texas worries that advocates of germline gene therapy may feel “[e]mboldened by a
new, powerful array of techniques … adhering to a theory of genetic determination of
simple and complex human characteristics ..” and that they “seem ready to risk the
lives of their subjects and generations to come”‘2 For such critics, social and ethical
concerns override the potential benefit of the technology and they wonder whether the
technology is driven more by commercial interests than by social or individual
needs.’
W. Gardner, “Can Human Genetic Enhancement Be Prohibited” (1995) 20 J. Med. & Phil. 65.
“Ibid. at 65.
“Quoted in “Gene Therapy in Womb”, supra note 2.
D. Nelkin & M.S. Lindee, The DNA Mystique: The Gene as Cultural icon (New York: Freeman,
1995) at 174.
B. Davis, “Germline Therapy: Evolutionary and Moral Considerations (1992) 3 Hum. Gene
Therapy 361. See also A. MeLaren, Letter to the Editor, “Problems of Germline Therapy” 392:6677
Nature (16 April 1998) 645.
McLaren, ibid.
“P.R. Billings & S.A. Newman, supra note 5 at 4.
See comments raised in Y. Danis, supra note 43.
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E MARDEN AND D. NELKIN – GERMLINE GENE THERAPY
473
IV. Existing Regulation is Not Adequate to the Challenges Posed
by the New Technology
Despite ethical concerns, reviews of the technology are likely to focus almost ex-
clusively on technical considerations. This approach appears to be built into the regu-
latory structure. A 1996 Federal Register rule made clear that the FDA was to be the
primary agency in charge of reviewing gene therapy applications.” The FDXs man-
date, however, is limited to assuring the safety and efficacy of products. The agency is
not authorized, nor is it equipped, to integrate social and ethical concerns into review
procedures. Furthermore, it is unclear whether the FDA would even have regulatory
jurisdiction in a case of enhancement therapy, as the agency’s jurisdiction is limited to
food, drugs, cosmetics, medical devices, and biologics. The NIH’s responsibility for
overseeing novel gene therapies is also limited. The NIH has jurisdiction only over
proposals that are funded by the NIH or that take place in NIH-funded institutions.
While the agency added the RAC in 1974 to integrate social and ethical concerns into
genetic research funding decisions,” in 1996 it downgraded this Committee to an ad-
visory body.
In addition to their structural or statutory limitations, both the FDA and the NIH
are somewhat compromised by their dual roles as regulators and promoters of novel
technologies. A pamphlet produced by the FDA and the NIH declares in its introduc-
tion that, “FDA and NIH share a common goal of promoting the development of use-
ful, safe, and effective therapies for human disease.””
A. FDA Review
The FDA is one of the federal government’s premier science-based agencies. Its
mandate is to “ensure that (1) food is safe, pure, and wholesome; (2) cosmetics are
safe; [and](3) human and animal drugs, biological products and therapeutic devices
are safe and effective:’ The FDA mantra in public meetings and discussions is that
“sound science” underlies all regulatory decision making.” Its review of germline and
“See “Proposed Actions”, supra note 10. Note that cloning also has been assigned to FDA for
regulatory review, though that technology also raises pressing ethical and social questions. For an
evaluation of whether FDNs administrative authority really would cover cloning, see E. Price, “Does
the FDA Have Authority to Regulate Human Cloning?” (1998) 11 Harv. J.L & Tech. 619, online:
WL (JLR).
‘Krimsky, supra note 7.
6P.R. Burd, P.D. Noguchi & AJ. Grant, eds., Forum 1996 Gene Therapy (Rockville, Md.: Food
and Drug Administration, 1996) at 3, online: Food and Drug Administration Homepage
67 Agriculture, Rural Development, and Related Agencies Appropriation Bill, Senate Report No.
101-84, 135 Cong. Rec. 58874, 1st Sess. (1989) online: LEXIS (GENFED).
6″ See e.g. comments of Commissioner Jane E. Henney, M.D. at FDA Health Professional Organi-
zation Meeting, Bethesda, Maryland (8 February 1999).
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somatic cell gene therapy is scientifically-oriented and focuses on factors such as
safety and efficacy.
The FDAs technical focus is clear throughout its statements of policy. In an early
document laying out the basis of FDA regulatory authority over gene therapies, the
agency stated that
[e]xisting FDA statutory authorities, although enacted prior to the advent of …
gene therapies, are sufficiently broad in scope to encompass these new products
and require that areas such as quality control safety, potency, and efficacy be
thoroughly addressed prior to marketing.’
The FDA has authority over gene therapy under the Federal Food, Drug and
Cosmetic Act (“FFDCA”) and Section 351 of the Public Health Service Act
(“PHSA”). In a 1993 statement on its approach to gene therapy products, the FDA
made clear that it considers cellular products intended for use as gene therapy prod-
ucts subject to both these regulations:
Gene therapy products are defined for the purpose of this statement as products
containing genetic material administered to modify or manipulate the expres-
sion of genetic material or to alter the biological properties of living cells.
Some gene therapy products [e.g., those containing viral vectors] to be admin-
istered to humans fall within the definition of biological products and are sub-
ject to the licensing provisions of the PHS Act, as well as to the drug provisions
of the act [FFDCA].”
Section 35 1(a) of the PHSA identifies a biological product as
any virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component
or derivative, allergenic product, or analogous product … applicable to the pre-
vention, treatment, or cure of diseases or injuries of man.
The FFDCA defines “drug” to include
articles intended for use in the diagnosis, cure, mitigation, treatment, or pre-
vention of disease in man or other animals; and articles (other than food) in-
tended to affect the structure or any function of the body of many or other ani-
mals.!’
At the investigational stage, gene therapy products must be in conformity with 21
C.F.R. 312, which outlines procedures for clinical trials of Investigational New Drugs
(“INDs”). 2 Under the IND process,73 gene therapies are subject to rigorous review for
safety and efficacy. The aim of the IND review is to allow new drugs to be studied
“Application of Current Statutory Authorities to Human Somatic Cell Therapy Products and Gene
Therapy Products” 58 Fed. Reg. 53,248 (1993) [emphasis added, hereinafter “Application of Current
Statutory Authorities”].
“bid.
Foo4 Drug and Cosmetic Act, 21 U.S.C. 321(g)(1)(B) and (C) (1999).
,”Application of Current Statutory Authorities”, supra note 69.
“See 21 C.F.R. 312.2(a) (1999) (“Mhis part applies to all clinical investigations of products that
are subject to section 505 [new drugs] of the Federal Food, Drug and Cosmetic Act …”).
2000]
E. MARDEN AND D. NELKIN – GERMLJNE GENE THERAPY
while being made available to patients for treatment use.7′ Drugs in the IND process
are subject to stringent requirements including detailed clinical protocols,” safety re-
ports, ‘ extensive record keeping,” and continuing supervision by an Institutional Re-
view Board.” Moreover, any product subject to the IND process may be placed on a
clinical hold by the FDA,” which means that the FDA may indefinitely delay or sus-
pend a proposed clinical investigation if it is found that “[h]uman subjects are or
would be exposed to an unreasonable and significant risk of illness or injury”‘
The FDA’s review process is firmly oriented around the tenets of expertise and
risk evaluation. In a Guidance on the topic, the FDA set forth the regulatory consid-
erations that govern approval of gene therapy products. These include adherence to
the IND process, quality control, demonstration of reasonable safety, and careful
product testing for bioactivity and potency.” Ethical issues are not explicitly included
in these regulations.
Under the authority granted by the PHSA and the FFDCA, it is not clear whether
the FDA would have any regulatory authority over enhancement applications of
germline gene therapy.’ Statutory authority elucidates the FDA’s role in overseeing
articles intended to diagnose, cure, mitigate, treat, or prevent disease. Thus, the
agency is clearly involved when the technology is used for genetic disease. However,
enhancement therapies do not fit into these categories and, as a result, the agency has
no direct jurisdiction over manipulations aimed at affecting traits such as intelligence,
personality or appearance.
The FDA has stated that because its authority extends over products for disease or
conditions of human beings, it would regulate enhancement applications.” This posi-
T, See “Investigation New Drug, Antibiotic and Biological Drug Product Regulations: Treatment
Use and Sale” 52 Fed. Reg. 19466 (1987).
” 21 C.F.R 312.23(a)(6) (1999).
76 21 C.F.R. 312.32 (1998).
“21 C.F.R. 312.57 (1999), 312.62 (1996), 312.64 (1999).
U21 C.ER. 312.66 (1987).
79 21 C.ER. 312A2 (1999).
21 C.F.R. 312.42(b)(i) (1999).
FDA, Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy,
Research
(1998)
Evaluation
online:
for
Biologics
FDA,
Center
and
‘2 This argument was developed with respect to cloning by Price, supra note 64 at 641. Therein
Price concludes that enhancement or reproductive choice applications of human cloning would not be
subject to FDA regulation because they fall outside of the definitions of drug, medical device or bio-
logic in the FFDCA.
“It could be also argued that germline gene therapy is simply a combination of a medical diagnos-
tic technology, like genetic screening, and a fertility treatment, such as in vitro fertilization. In the
past, the FDA has not regulated such procedures, a position that is consistent with the fact that the
FDA is not permitted to regulate the practice of medicine. See W.L. Christopher, “Off-Label Drug
Prescription: Filling the Regulatory Vacuum” 48 Food & Drug W. 247 at 250-56 (detailing the judi-
cial indication that the FDA’s supervision does not extend to regulation over the practice of medicine);
MCGILL LAW JOURNAL!REVUE DEDROITDE MCGILL.
[v(ol. 45
tion is, however, subject to debate. The FDA’s authority has never extended to the
regulation of medical interventions per se.” A gene alteration to enhance a foetus’
qualities is a medical intervention, analogous to cosmetic treatments or reproductive
technology such as cloning, and thus it is unlikely that the FDA would have jurisdic-
tion.” Moreover, the agency acknowledges that off-label uses of approved drugs are
permitted without further regulatory review in cases where they are instigated by a
physician and where the risk to the patient is no greater than that found in the ap-
proved indication.’ Thus, it becomes possible once the technology is approved for
disease uses scientists could engage in “off-label” enhancement applications of germ-
line gene therapy.
To its credit, the agency is clearly searching for a basis to oversee this radical
technological advance.” In response to a query about the FDA’s ability to include so-
cial and ethical considerations in decision making, Dr. Philip Noguchi, Director of the
Division of Cellular and Gene Therapies in the Center for Biologics Evaluation and
Research, made clear that the FDA does factor in a range of ethical issues stating that
“we do that via presentations and discussion at the RAC [NIH] meetings. We have
held joint meetings on in utero, genetic enhancement and the potential use of lentiviral
vectors:” Yet, these meetings are not written into the FDA’s policy on gene therapy,
and the regulations do not provide the FDA with any explicit avenue for considering
ethical issues on its own.”
see also “Misuse of Prescription Drugs, Before the Subcomm. on Human Resources and Intergov-
emmental Relations, Comm. on Gov’t Reform and Oversighe’ (1996) (statement of Michael Fried-
man, Deputy Commissioner for Operations, FDA) (‘The history of the Act [FFDCA] indicates that
Congress did not intend FDA to interfere with the practice of medicine.”); 142 Cong.Rec. S12,024
(daily ed. 30 Sept. 1996) (statement of Senator Frist) (“While the FDA regulates medical devices and
pharmaceuticals, it has no authority to regulate the general practice of medicine.’).
Price, supra note 64.
The FDA is not permitted to regulate the practice of medicine. See E. Marden & D. Nelkin,
“Cloning: A Business Without Regulation” (1999) 27 Hofstra L. Rev. 569 at 573-74. See also Price,
supra note 64.
See Washington Legal Foundation v. Friedman, 13 FSupp.2d 51 (D.C. 1998).
” Indeed, in December 1994, Philip Noguchi and Amy Patterson of the FDA’s Cell and Gene
Therapies Division at the Center for Biologics Evaluation and Research, urged the RAC to establish a
subcommittee to examine the issues surrounding “gene therapy in fetuses”. See H. Gavaghan, “Future
Perfect or Imperfece’ (1995) 1 Nature Medicine 186 at 187.
‘3E-mail from Dr. Philip Noguchi to Emily Marden (16 April 1999).
Because of general concerns that FDA is not equipped to integrate moral and ethical concerns,
there is a move afoot to ensure RAC discussion of proposed novel gene therapy studies prior to FDA
approval. See “Gene Therapy: RAC Public Discussion of Gene Therapy Protocols Prior to FDA Ap-
proval Will be Guaranteed by NIH’ F-D-C Rep. (‘The Blue Sheet’) (30 Sept. 1998) [hereinafter
“RAC Public Discussion”].
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E. MARDEN AND D. NELKIN – GERMLINE GENE THERAPY
B. NIH Review
The NIH’s supervision of germline gene therapy is constrained in a different way.
The NIH does provide a forum for the consideration of the social and ethical issues
raised by germline gene therapy through the RAC and its Gene Therapy Policy Con-
ferences, but these outlets have a minimal regulatory impact. The NIH is not a regu-
latory agency per se; rather, it underwrites medical research. The agency reviews re-
search and clinical protocols in the context of whether they deserve funding. In this
sense, the NIH’s “jurisdiction” is limited to NIH-funded protocols or protocols being
carried out in NIH-funded institutions.’
The NIH did broaden its consideration of genetic research to include non-
technical matters in 1974, in response to intense public controversy over recombinant
DNA experiments.” At that time, the NIH established the RAC to assure adequate su-
pervision of clinical research involving recombinant DNA’ The RAC was given the
responsibility for reviewing protocols on both scientific and social grounds and the re-
sponsibility to recommend approval or disapproval to the NIH Director” Toward this
end, the RAC held regular public hearings which served as a forum for debate on a
range of scientific, social and ethical issues. The group continued to play this role and
to dictate NIH Policy on novel genetic science until 1996 when, pursuant to a new
rule, the RAC’s role was reducedY
The RAC no longer has any formal role in approving or disapproving protocols.
Its role is now advisory and instead of having systematic review powers over all new
genetic technologies, the RAC serves as an advisor to the NIH Director only for those
technologies deemed by at least three RAC members to require further review.” In
addition, the RAC’s membership has been reduced from twenty-five to fifteen mem-
bers. The role of the Committee as a public forum has also been changed. The RAC
now organizes Gene Therapy Policy Conferences (“GTPC”) to discuss social and
Hypothetically, a privately funded researcher engaging in enhancement therapies may be able to
avoid the regulatory process outright and just proceed with the application. In addition, a researcher
could avoid the public debate generated by the RAC, by using private funding and submitting to FDA
safety and efficacy evaluation alone. In fact, according to one FDA official, this situation has already
arisen once.
“‘ See National Institutes of Health, Office of Recombinant DNA Activities (“ORDA”), Recombi-
nant DNA Advisory Committee Charter, online: Office of the Recombinant DNA Activities Home-
page
ter]; and Krimsky, supra note 7.
See generally Krimsky, supra note 7.
3 biL See also ORDA Charter, supra note 91.
See J. Beach, “The New RAC: Restructuring of the National Institutes of Health Recombinant
DNA Advisory Comniittee” (1999) 54 Food & Drug LJ. 49. See also “Proposed Actions”, supra
note 10. For later implementation of these changes, see “Recombinant DNA Research: Action Under
the Guidelines” 62 Fed. Reg. 4782 (1997); and “Actions Under the Guidelines”, supra note 10.
“See “Proposed Actions”, supra note 10. For later implementation, see “Actions Under the Guide-
lines”, supra note 10.
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ethical considerations in response to issues pertaining to gene therapy policy.’ The
idea behind the change was to streamline the regulatory process by separating the
regulatory and monitoring responsibilities of the RAC. Dr. Harold Varmus, Director
of the NIH, had hoped that the redirection of all regulatory concerns to the FDA
would allow the RAC to focus on the broader implications of novel gene therapy pro-
posals” including social and ethical considerations such as:
(1) Identifying novel human gene transfer experiments deserving of public dis-
cussion … (2) Identifying novel ethical issues relevant to specific human appli-
cations of gene transfer and recommending appropriate modifications to the
Points to Consider documents. (3) Identifying novel scientific and safety issues
relevant to specific human applications of gene transfer … (4) Publicly review-
ing human gene transfer clinical trial data. (5) Identifying broad scientific and
ethical/social issues relevant to gene therapy research as potential Gene Ther-
apy Policy Conference Topics.7
However, limiting the RAC’s role had the effect of concentrating regulatory re-
view in the FDA where social and ethical issues are not formally considered.” One
critic of germline gene therapy described the new RAC as mere window dressing:
“The RAC has absolutely no standing in this debate. No power. No regulatory posi-
tion. The FDA is the only player here:”
The RAC review of Anderson’s pre-protocols in January, 1999 demonstrates the
limits of the current regulatory structure. After hearing testimony from scientists, cli-
nicians, families, policy makers, individuals, and groups of concerned citizens, the
RAC concluded that “[a]t present there is insufficient preclinical data to support the
initiation of clinical trials involving prenatal gene transfer’
Its report listed in detail
15 separate efficacy and risk issues that require additional data, including information
on the specificity of genetic manipulations, the safety of clinical design, and the risk
to the foetus’and the mother. The RAC also appended to its list a set of unspecific
concerns about informed consent issues and social and legal implications.” There was
no indication of what these issues encompassed and how they might be addressed.
‘”Proposed Actions”, supra note 10. See also NIH Gene Therapy Policy Conferences (“GTPC’),
online: Office of Biotechnology Activities
cessed: 17 March 2000).
“Perils in Free Market Genomics” Nature 392:6674 (26 March 1998) 315.
“Proposed Actions”, supra note 10 at 729.
61 Fed. Reg. at 59,727. Apparently, the concentration of regulatory authority at FDA and the lack
of systematic consideration of ethical issues at that agency has raised widespread concem. In Septem-
ber 1998, an industry trade publication reported that NIH and FDA were thinking of re-integrating
RAC review into the regulatory process. See “RAC Public Discussion”, supra note 89.
” Quoted in D.N. Gianelli, “Prenatal Gene Therapy Put on Hold-For Now” American Medical
News (1 February 1999), online: WL (HTHNEWS).
“, See NIH Gene Therapy Policy Conference: Prenatal Gene Transfer: Scientific, Medical and
Ethical Issues, Conclusions (1999) online: Office of Recombinant DNA Activities Homepage
“‘ See ibid.
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E. MARDEN AND D. NELKIN- GERMUNE GENE THERAPY
Those attending the meeting were certain that despite the social and ethical questions,
the technology would ultimately be approved. Dr. Paul Billings of the Council for Re-
sponsible Genetics noted that the technology was “going to go ahead. It’s just a matter
of time.”” Indeed, Dr. Anderson hopes to introduce a final proposal to the panel in the
next few years.”‘
Ultimately, the regulatory process does not meet the challenges of the technology.
John Robertson, professor of pediatrics, has observed that “[t]he effects of [gernline
gene therapy] would have reverberations for society, not just the individual patient,
and our current framework for assessing risks and benefits doesn’t account for socie-
tal risks.”‘”
C. European Policy
Europe has taken a very different tack in determining the fate of gennfine gene
therapy. As the United States moves toward a regulatory regime that focuses only on
science and efficacy considerations, Europe has chosen to address germline gene
therapy through the broader framework of international human rights law as a social
and ethical issue.”” The operating principle is that human beings share a genetic heri-
tage which may change naturally, but which should not be purposively changed
through human intervention. In Europe, the sense is that altering the germline would
compromise human dignity.”
After almost a decade of study, the Committee of Ministers of the Council of
Europe!’ adopted the Convention for the Protection of Human Rights and Dignity of
“5 Quoted in Gianelli, supra note 100.
“=Ibid. One of Anderson’s colleagues in developing gene therapy predicted that “the technology to
do germline gene therapy … will become available in the next four to five years:’ See T. Friend, supra
note 42.
‘ Quoted in L. Seachrist, “Prenatal Gene Therapy Could Require New Ethical Framework”
Bioworid Today (12 January 1999), online: WL (HTHNEWS). See “Perils in Free Market”, supra
note 97 (noting the “sweeping significance” that germline gene therapy would have and the need for
some form of regulatory review).
” For an interesting examination of different international perspectives on the ethical questions
raised by gene therapy, see D.RJ. Macer et aL, “International Perceptions and Approval of Gene
Therapy” (1995) 6 Hum. Gene Therapy 791.
“5 See J. Robertson, “Oocyte Cytoplasm Transfers and the Ethics of Germ-Line Intervention”
(1998) 26 J.L. Med. & Ethics 211 at 216.
“a The Council of Europe has 38 member states all of which are also members of the European
Union. Established in 1949, the Council of Europe serves three main functions: it protects funda-
mental human rights and democratic pluralism, promotes European cooperation on solving social ills,
and fosters appreciation of Europe’s “multicultural identity” (Statute of the Council of Europe (5 May
1949) 87 U.N.T.S. 103, 104-105, arts. 1(a), (b); D. Pinto, “The Council of Europe in Action” in Se-
curing The Euro-Atlantic Bridge: The Council of Europe and the United States, J.E. Mrox, D. Pinto &
R Rosentiel, eds. (New York: Institute for East-West Studies, 1993) 27).
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[Vol. 45
the Human Being with Regard to the Application of Biology and Medicine.”1 The
Convention, to which twenty-two nations are signatories, states that genetic manipula-
tion may be undertaken for purposes of prevention, diagnosis, or therapy, but only if it
does not aim to introduce a permanent modification in the genome.”‘ This convention
effectively rules out any uses of germline gene therapy.’
Conclusions
In this era of radical biotechnology, scientific advances present profound social
and ethical dilemmas. Critics of germline gene therapy question the implications of
tampering with the germline, the meaning of such interventions for human dignity,
and the potential for eugenic abuse. There is the additional concern over how gene
manipulation will affect future generations. Yet, driven by scientific hubris, commer-
cial interests, and media hype, this technology is moving inexorably towards clinical
application with minimal public discussion of these issues. Ultimately, the regulatory
system, structured to address questions of safety and efficacy, effectively displaces
any consideration of the social and ethical implications of scientific developments.
In the past, similar social issues have generated significant and often tumultuous
public debate. For example, the consequences of the possible release of genetically
engineered organisms into the environment were the focus of active public discus-
sions during the 1970s. Concerns about harming future generations prompted wide-
spread public opposition to nuclear power and the early development of in vitro fer-
tilization provoked widespread ethical debate over the potential for eugenic abuses. In
recent years, however, public involvement in technological decisions has radically de-
clined, reflecting a broader shift from public activism to personal consumerism and
the ascendance of commercial interests in the biosciences. There is a growing ten-
dency to reduce ethical issues to technical questions and to defer to scientific exper-
tise.
As a result, today, when scientists have the power to radically alter the human ge-
netic structure, there is little public discussion or debate about the ethical and social
consequences of this technology. There are few avenues through which bioethical
concerns may be brought to the public arena in order to extend the public’s knowl-
edge and interest in these issues. In a world where biotechnology poses profound
“1 Convention on Human Rights and Biomedicine, supra note 11, art. 13.
“‘ For background on Europe’s decision, see S. Murray, “As Science Races Forward, Lawmakers
Try to Catch Up” Wall Street Journal Europe (4 March 1997), online: WL (WSJ-EURO). Europe has
also sought to address social and ethical issues in regulating somatic cell gene therapy. See C.F De
Jager, “The Development of Regulatory Standards for Gene Therapy in the European Union” (1995)
18 Fordham Int’l L.J. 1303.
… See Convention on Human Rights and Biomedicine, supra note 11. Note also that as of June
1998, it appeared that Canada is considering outlawing forms of research including “gene alteration …
that involves human gemline cells or human zygotes or embryos”. See W. Kondro, “Leaked Docu-
ment Indicates Canada’s Future Stance on Human Research” (1998) Lancet 1868.
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E. MARDEN AND D. NELKIN – GERMLINE GENE THERAPY
481
challenges to the biological and social order, it is time to consider developing new
fora for public debate so that social and ethical concerns may play a more significant
role in the review and regulation of science.
