Psychological Features of Human Reproductive Cloning: A Twin-Based Perspective

Debates surrounding the psychological implications of human reproductive cloning (HRC) escalated in 1997, following the 1996 birth of Dolly, the cloned Scottish lamb. For the first time, human cloning was no longer a vague uncertainty but a real possibility. Aside from the physical risks to which cloned persons might be subjected, there was concern over psychological implications associated with family structure and relationships. Would cloned persons be deprived of autonomy and independence? Would parents impose unfair expectations on children who were their genetic replicas? Since then, purported attempts to clone a child¹ have kept worries over HRC's societal consequences in the public consciousness.

Possible sequelae of HRC have been addressed in journal articles,^2,3 books,^4,5 edited volumes,⁶ legal symposia,⁷ newspaper and magazine articles,^8,9 and scientific documentaries.¹⁰ The National Bioethics Advisory Commission presented an array of hypothetical consequences of HRC, many involving potential harm to cloned children and adverse effects on society.¹¹

A review of the various sources reveals inappropriate reference to cloned children as "genetic twins" of their donors and neglect or misrepresentation of scientific twin research findings. This is unfortunate because twins and twin research offer the best available model (although not the only model) for informed evaluation of HRC's psychological effects. The present essay will address the question, "Who is a twin?" and examine the ways in which twin studies can clarify thinking about clone-donor resemblance, individuality, and social relationships. Some research designs for further addressing various concerns will also be proposed.

CRITERIA FOR TWINSHIP
Identical (monozygotic, or MZ) twins are clones (genetic replicas of another individual or organism), but clones are not identical twins. More formal definitions include "a plant, animal, or other organism that is genetically identical to its parent," or "a collection of organisms, cells, or molecular segments that are genetically identical, direct descendants of a single parent by asexual reproduction."¹² It might be objected that MZ twins are genetically identical to each other, not to a parent, and so do not fit these definitions. However, if we consider that MZ twinning results when a zygote divides between the first and 14th postconceptional day,¹³ it is possible to consider the single zygote as the "parent" that gives rise to an identical copy.

Despite MZ twins' (and clones') direct descent from a genetically identical other, members of selected pairs may show some genetic differences. These are variously explained by postzygotic chromosomal nondisjunction, differential X-chromosome inactivation in female pairs, differential gene imprinting, and mutations for autosomal single-gene diseases.¹⁴ Nevertheless, MZ twins are more alike than any other pair of individuals across all measured behavioral and physical traits, and even separately reared twins show striking similarities.

Establishing twinship criteria is important because of frequent reference to cloned children as "twins" or "delayed genetic twins" of their parents or other individuals.¹⁵ These terms convey concepts of sameness and intimacy, and could impose unfair expectations and demands upon individuals who do not fit the criteria. Four twinship criteria, including discussion of exceptional cases, are presented below.

CONCURRENT CONCEPTION
A unique feature of MZ twins is that co-twins are conceived at the same time. In contrast, clones and their parent donors would be conceived years apart, and clones and their donor siblings would be conceived at least 9 months apart.

SHARED BIOLOGIC PARENTS
MZ twins share their parents in a biologic sense because their mother released the egg that was fertilized and she carried them throughout the pregnancy. Half the twins' identical genes come from their mother and half come from their father. However, donors and clones share their parents only in a technical sense. This is because, despite their identical genes, the donor's mother (the clone's grandmother) gestated the donor but not the clone. Furthermore, unless the donor gestated the clone created from one of her cells, the 2 would not share mitochondria. Mitochondria are passed down through families on the maternal side, and a clone created from a father would not share his mitochondria unless gestated by his sister or mother. However, not sharing mitochondria should have little effect on clone-donor similarity because mitochondria represent a very small fraction of the genome, and are more directly associated with cellular functioning than with phenotypic expression.

COMMON INTRAUTERINE ENVIRONMENT
Twins develop in the same intrauterine environment, yet this environment is not truly the same for MZ twins. Approximately two thirds of MZ twins (those resulting from delayed zygotic division) are affected by mutual circulation in utero (fetal anastomosis) that can produce co-twin differences in size and health.¹³ Interestingly, some studies have shown greater intellectual and personality similarities among later-splitting twins than early-splitting twins.¹⁶ Donors and clones would share neither intrauterine environments nor prenatal events. However, adverse prenatal events are more closely tied to MZ co-twin differences, not similarities. It is, therefore, possible that a donor and a clone might be more physically alike in certain traits than MZ twins because each would have been gestated separately, unaffected by the adversities typical of multiple-birth pregnancies.

COMMON GENERATIONAL AND HISTORICAL EVENTS
Donors and clones would belong to different generations and so would not experience the same historical events in the same way. Cloned siblings might be part of the same generation, but their experiences of historical events might differ because of their age difference. In contrast, MZ twins belong to the same generation and so would be similarly subjected to, and affected by, historical and societal changes. Twins reared in different homes or cultures raise some exceptions to this aspect of twinship because they could be differently affected by historical and generational events, but would still be considered twins.^13,17

KEY QUESTIONSHow alike would a cloned child be to his or her parent donor, relative to MZ twins?
Research demonstrates that MZ twins separated at birth and reunited as adults show significant resemblance in height, brain waves, and intelligence (more so than dizygotic [DZ] twins), consistent with genetic influence on those traits.^13,18 MZ twins also show resemblance, albeit somewhat less so, for personality traits, vocational interests, and sexual orientation.¹⁹ Clone-donor similarity would be expected to be highest for traits with the largest genetic components (eg, height, brain waves, and intelligence), although as with MZ twins, it would not be perfect similarity. It would also not be surprising if clones and donors showed greater resemblance to one another than MZ twins in birth weight which, as indicated above, is affected by adverse prenatal events. It is also possible to imagine greater average clone-donor than twin-twin similarity in some other measured traits, although not in all. For example, MZ twins often differentiate themselves behaviorally, so that one twin may be somewhat more outgoing or assertive than the other when they are together in social situations. This might be less likely to happen with clones and donors, who would have different friends and social groups.

Physical characteristics such as hair color and eye color are strongly genetically influenced, so it is likely that clones and donors would be highly concordant for such traits. However, the age difference between them would most likely preclude public recognition of such pairs, whereas MZ twins are identifiable at all ages.²⁰ This "hidden" aspect of clones and donors would help ensure their privacy. Clones and donors may show lower average levels of resemblance than MZ twins for some complex behavioral traits and abilities, such as musical talent or athleticism. While clones and donors are born with the same genetic predispositions, their respective environments may not be conducive to matched expression of those predispositions. An award-winning basketball-playing father might have a potentially talented son, but if his son's school stresses other activities, his son's athletic abilities may be expressed in other ways or not at all.

However, based on the finding that some MZ twins raised in different cultures show striking similarities in mental abilities, temperamental traits, and unusual habits, we would anticipate that clones and donors could be very similar in some behaviors, despite their different environments.¹⁷ Thus, the only correct response to this question is that a cloned child may be very similar to a donor parent in all traits, some traits, or a few traits.

Would the individuality and uniqueness of cloned individuals be threatened?
Most psychological twin studies demonstrate greater social closeness and affiliation between MZ twins than between DZ twins. However, social closeness does not imply loss of individuality, and most MZ twins enjoy their relationship and the emotional support, trust, and understanding it uniquely affords.

MZ twins are more alike than any other pair of people, but it is not perfect resemblance, as indicated. These differences are most likely linked to the social differentiation displayed by MZ twins and other multiples. Some older twin studies have found that MZ twins reared apart (or living apart) were more alike in extraversion and divergent thinking than twins reared together (or living together).^21,22 More recent studies have not confirmed these findings,^23,24 but interviews with a number of MZ twins suggest that there is some validity to the earlier findings.¹⁷

If MZ twins' individuality and autonomy were threatened because of their physical and behavioral resemblance, then they should be overrepresented among psychiatric populations, but this has not been found to be true.²⁵ In fact, a recent Danish study found a lower rate of suicide among twins, possibly as a consequence of the social support they provide one another.²⁶ Furthermore, if MZ twins' identity and autonomy were threatened by the presence of a twin, then reunited twins should not establish close relations with one another, but they do. In fact, both MZ and DZ twins expressed greater feelings of closeness and familiarity toward their newly found co-twin than toward the adoptive siblings with whom they were raised.²² Since it appears that the identity and autonomy of most MZ twins are not diminished by their physical and behavioral resemblance, then this should not be a concern for a donor and clone, whose age and generation would differ.

Would novel family relationships generated by cloning prove harmful to family members?
Features distinguishing MZ twin relationships from those of other twins and siblings include higher levels of attachment-specifically, security and proximity.²⁷ Twins (both MZ and DZ) indicated higher levels of intimacy with their co-twins than with their friends, although MZ and DZ twins did not differ in this dimension. MZ twins were, however, more likely than DZ twins to identify their co-twin as their best friend.²⁸ Another study found that the quality of DZ twin relationships depended on frequency of contact, while this effect was minimal or absent in MZ twinships.²⁹The foregoing suggests potential psychological benefits associated with HRC. Perhaps empathy and understanding between cloned children and their parents would be heightened.

Would parental expectations of behavioral similarity in genetically identical offspring be psychologically damaging to these children?
Ordinary parents entertain a range of expectations for their children. Donor parents, like ordinary parents, would also have goals and expectations for their children. In both types of families, expectations for children might coincide with parents' own accomplishments or might depart dramatically. Another way of considering the above question is to ask whether MZ twins who are the most alike are the least happy. Indirect evidence, such as the fact that thousands of twins attend events celebrating their twinship each year, suggests that the answer is no.

There is nothing inherently damaging or detrimental about sameness or closeness in parent-child or sibling relations. Denying similarities between cloned children and their parents and siblings might be damaging to their identities and interests.

Other investigators have recently posed additional relevant questions to MZ and DZ twins and singletons.31 Based on their responses, they concluded that cloned individuals might perceive close physical and emotional connections to a donor as positive, might suffer if others regarded them as less than complete individuals, and might find the idea of not being born a clone unpleasant. The number of individuals interviewed was small, so this work should continue. I am currently gathering data from mothers of twins to assess their perspectives on such issues.

CONCLUSION
It is impossible to forecast every possible outcome (either positive or negative) from HRC. It is, therefore, mandatory that concerns be addressed using better models and research methods to anticipate future consequences.

Assisted reproductive technologies (ART), once a novel set of procedures that some feared would destroy the nature and structure of families, are now widely practiced. Most important, ART has allowed countless infertile couples to raise families.

Available human models are useful for sharpening thinking about issues raised by HRC. Paradigms presented by Levick are exemplary in this respect, but have yielded considerable speculation (mostly negative), in the absence of empirical data.³⁰ A quote from his book is illustrative: "a child too dissimilar to a narcissistic parent may find his dissimilarity quite detrimental. However, resemblance may carry its own problems, enhancing parental expectations that the child will be like the parent. Such is apt to be the plight of a self-clone." (p. 95).

Assessing these alternative outcomes could be accomplished by detailed longitudinal studies of unusually similar and dissimilar parent-child and sibling pairs. A televised segment of 4 very similar looking mother-daughter pairs underlined the pleasure they gained from their shared qualities and interests. Exceptions to this outcome may be expected, but knowing that similarity does not imply dissatisfaction-and may enhance satisfaction-is central to this debate.

There is a near-exclusive focus by Levick on negative motivations, mostly narcissism, with respect to parents choosing to clone.³¹ No doubt, there are also ordinary biological parents who have children for less than admirable reasons-to keep their marriage together, to continue the family business, to have caretakers in old age. Perhaps an infertile couple would clone a son or daughter simply out of love for a child.

In conclusion, based on my research experience with MZ twins and the experiences of other investigators, a number of concerns about HRC's potential psychological costs appear to be of less consequence than generally presumed. At the same time, several benefits seem likely. It is important to note, however, that even if some issues can be resolved and some benefits found, this would not necessarily justify the procedure-just additional dialogue and discussion.

Dr Segal is professor of psychology at California State University, Fullerton, and director of the Twin Studies Center there. She is the author of 2 books on twins: Entwined Lives: Twins and What They Tell Us About Human Behavior (Plume, 2000) and Indivisible by Two: Lives of Extraordinary Twins (Harvard University Press, 2005). She reports no conflicts of interest concerning the subject matter of this article.

References:

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