Human cloning
Human cloning involves the asexual replication of human genetic material to produce identical copies of cells, embryos, or potentially full individuals, primarily through somatic cell nuclear transfer (SCNT), where the nucleus of a somatic cell is inserted into an enucleated oocyte.[1][2] This process distinguishes between reproductive cloning, intended to yield a viable human organism genetically identical to the donor, and therapeutic cloning, aimed at generating embryonic stem cells for medical applications without gestation.[3] Despite successes in animal models, such as the 1996 cloning of Dolly the sheep, no verified instance of human reproductive cloning has been achieved, with reported attempts marred by scientific fraud or lack of substantiation.[4] Therapeutic cloning has advanced further, enabling the derivation of patient-specific stem cells from cloned human embryos as early as 2013, though efficiency remains low and ethical concerns persist regarding embryo viability and destruction.[5][6] The technique's development stems from foundational work in nuclear transfer, but human applications face profound biological hurdles, including high rates of developmental abnormalities observed in cloned animals, epigenetic reprogramming failures, and premature aging syndromes.[7] Controversies encompass not only these technical inefficiencies but also profound ethical debates over human dignity, the commodification of life, and risks of psychological harm to clones, such as identity crises or societal stigmatization.[8] Legally, reproductive human cloning is prohibited in approximately 46 countries, with many others imposing moratoriums or restrictions on therapeutic forms, reflecting global consensus on its perils amid divergent views on embryo status.[9][10] While proponents argue potential benefits for infertility treatment or organ regeneration, empirical data underscore unresolved safety issues, underscoring cloning's status as a frontier technology constrained by both science and principle.[11]Definitions and Scope
Core Definitions
Human cloning is the artificial creation of a genetically identical copy of a human organism or its cells, typically through techniques that replicate the nuclear DNA from a donor somatic cell.[1] This process differs from natural identical twinning, which occurs spontaneously during embryonic development without human intervention.[2] The most discussed method for human cloning is somatic cell nuclear transfer (SCNT), in which the nucleus of a donor somatic cell is transferred into an enucleated oocyte (egg cell), followed by chemical or electrical stimulation to initiate division.[12][13] Reproductive cloning refers to the use of such techniques to produce a viable, live-born human genetically identical to the donor, with the cloned embryo implanted into a uterus for gestation.[1][2] In contrast, therapeutic cloning—also known as somatic cell nuclear transfer for research—generates cloned embryos solely to derive embryonic stem cells for medical applications, such as tissue repair or disease modeling, without intent to create a born individual.[1][11] A third category, gene or molecular cloning, involves replicating specific DNA segments or genes in vitro for research purposes but does not produce whole organisms or cells and is not typically encompassed under "human cloning" in ethical or policy discussions.[14][1] These definitions emphasize genetic identity at the nuclear level, though mitochondrial DNA from the oocyte donor may introduce minor variations; full genomic identity would require cloning the donor's oocyte as well.[12] No verified instances of successful human reproductive cloning exist as of 2025, distinguishing it empirically from animal cloning successes like Dolly the sheep in 1996.[1]Types of Human Cloning
Human cloning is classified into reproductive cloning and therapeutic cloning, with the latter sometimes encompassing research applications; a third category, gene cloning, involves replicating human DNA segments but does not produce organisms or embryos.[1] Reproductive cloning aims to generate a complete, genetically identical human individual by transferring a somatic cell nucleus into an enucleated egg, developing the resulting embryo to the blastocyst stage, and implanting it into a uterus for gestation.[2] This process mirrors the technique used to clone Dolly the sheep in 1996, but applied to humans, with the intent of producing a viable offspring.[1] No verified instances of successful human reproductive cloning have been documented as of 2023, due to technical inefficiencies, high failure rates observed in animal models, and ethical prohibitions in most jurisdictions.[12] Therapeutic cloning, also termed somatic cell nuclear transfer for research or embryo cloning, creates cloned embryos specifically to derive patient-matched embryonic stem cells for regenerative medicine or disease modeling, without plans for implantation or birth.[11] The cloned embryo is cultured to the blastocyst stage, from which the inner cell mass is extracted to produce pluripotent stem cells capable of differentiating into various tissue types, potentially avoiding immune rejection in therapies.[1] This method has been pursued to treat conditions like Parkinson's disease or spinal cord injuries, though human applications remain experimental and limited by low success rates in nuclear reprogramming, typically below 5% in mammalian models.[15] Advances in induced pluripotent stem cells have partially supplanted therapeutic cloning needs, offering non-embryonic alternatives for cell generation.[3] Gene cloning, distinct from organismal cloning, replicates specific human genes or DNA fragments using recombinant DNA technology in host organisms like bacteria or yeast, primarily for studying gene function, producing proteins, or gene therapy vectors.[1] While integral to molecular biology and human genomics research, such as the Human Genome Project completed in 2003, it does not involve creating human embryos or individuals and thus falls outside the scope of debates on human reproductive or therapeutic cloning.[1]Historical Development
Early Theoretical Foundations
The theoretical foundations of human cloning trace back to late 19th- and early 20th-century embryological studies on cellular totipotency, which demonstrated that individual cells from early embryos could develop into complete organisms. In 1885, Hans Driesch separated the blastomeres of two-celled sea urchin embryos, showing that each cell retained the full genetic potential to form a viable larva, thus establishing artificial embryo twinning as a form of cloning.[4] This work highlighted the regulative capacity of early embryonic cells, a principle later extended to vertebrates. In 1902, Hans Spemann replicated twinning in salamander embryos by constricting fertilized eggs with a fine hair loop, producing identical twins from cells at the two- to four-cell stage and confirming that early blastomeres in higher animals possess totipotent nuclei capable of directing full development.[4] Spemann's research advanced further with experiments on embryonic induction, culminating in the 1924 "organizer" concept—where dorsal lip tissue from a salamander gastrula induced a second embryo when transplanted—earning him the 1935 Nobel Prize in Physiology or Medicine.[16] In 1928, Spemann performed rudimentary nuclear transfers using salamander embryos, relocating nuclei from early cleavage stages into enucleated eggs and observing development guided by the transplanted nucleus, which underscored the nucleus's dominant role in heredity over cytoplasmic factors.[4] These findings challenged August Weismann's 1892 germ plasm theory, which posited irreversible differentiation and separation of germinal from somatic lines, by suggesting nuclei might retain developmental plasticity. The pivotal theoretical proposal for cloning differentiated cells came in Spemann's 1938 book Embryonic Development and Induction, where he outlined a "fantastical experiment": transplant the nucleus of a differentiated embryonic cell into an enucleated unfertilized egg of the same species to determine if it could orchestrate normal ontogeny.[16] Spemann viewed this as technically unfeasible at the time due to the inability to micromanipulate mammalian or human cells precisely, but it formalized the hypothesis that somatic nuclei could be reprogrammed by egg cytoplasm to regain totipotency. This concept directly anticipated somatic cell nuclear transfer (SCNT), the technique central to later animal cloning and proposed for human reproductive cloning, implying that human development could theoretically be replicated from a differentiated donor nucleus if ethical and technical barriers were overcome.[16]Key Experimental Milestones
The first reported attempt to clone human embryos using somatic cell nuclear transfer (SCNT) occurred in November 2001, when researchers at Advanced Cell Technology announced the creation of embryos from human leg cells that developed to the six-cell stage before arresting; however, independent verification was limited, and the embryos were not viable for further development.[17] In 2004, South Korean scientist Hwang Woo-suk claimed to have derived patient-specific human embryonic stem cell lines via SCNT, reporting the creation of 11 lines from 242 oocytes using cumulus cells; these results, published in Science, were hailed as a breakthrough in therapeutic cloning but were later retracted in 2006 after evidence emerged of data fabrication, ethical violations in egg procurement, and no actual stem cell derivation.[18] A verified advancement came in 2008, when a team led by Andrew French and Samuel Wood at Stemagen Corporation reported the creation of five human blastocyst-stage embryos via SCNT using skin cells from female donors and oocytes from the same donors, though no embryonic stem cell lines were derived due to technical limitations in culturing. The first confirmed derivation of human embryonic stem cells through SCNT was achieved in May 2013 by Shoukhrat Mitalipov's team at Oregon Health & Science University, who transferred nuclei from fetal somatic cells into enucleated human oocytes, yielding viable blastocysts from which two pluripotent stem cell lines were established; this demonstrated efficient reprogramming in human cells, overcoming prior inefficiencies seen in animal models.00384-9)[19] Subsequent refinements included a 2014 Japanese study by Masato Nakagawa and team, who successfully generated induced pluripotent stem cells as a comparison but also advanced SCNT protocols to derive stem cells from adult human fibroblasts, confirming the 2013 findings with higher efficiency using caffeine to prevent premature activation. No verified reproductive human cloning—intended to produce a live birth—has occurred, with all claims, such as the 2002 announcement by Clonaid of a cloned infant named "Eve," lacking empirical evidence or independent confirmation.[1]Modern Attempts and Claims
In December 2002, Clonaid, a company affiliated with the Raelian religious group, announced the birth of a baby girl named Eve, claimed to be the world's first human clone produced via somatic cell nuclear transfer from her 31-year-old American mother's DNA.[20] [21] Clonaid's CEO, Brigitte Boisselier, stated the cloning occurred outside the United States and that Eve was healthy, but provided no DNA evidence, medical records, or independent verification, citing privacy concerns.[22] [23] By 2004, Clonaid escalated claims to having produced 14 human clones, yet refused offers for third-party genetic testing, leading to widespread dismissal by scientists as unsubstantiated publicity.[24] Concurrent efforts involved Italian fertility specialist Severino Antinori, who in April 2002 claimed one of his patients was two months pregnant with a cloned fetus, intending to produce the first cloned baby by late 2002 or early 2003 to aid infertile couples.[25] [26] Antinori, previously known for pioneering preimplantation genetic diagnosis, partnered with Cypriot-American physician Panayiotis Zavos in 2001 to pursue human reproductive cloning using donated eggs and somatic cells from infertile individuals.[27] These announcements drew immediate condemnation from scientific bodies, including the European Society of Human Reproduction and Embryology, for ethical violations and safety risks, with no subsequent birth confirmations or peer-reviewed data emerging.[28] Zavos continued independent claims into the 2000s; in February 2004, he reported implanting a cloned embryo into a woman, which he later admitted failed to result in pregnancy.[29] By April 2009, Zavos asserted he had cloned 14 human embryos, implanting 11 into four women's uteri, predicting clones within months, but offered no verifiable proof beyond self-reported procedures conducted in undisclosed locations to evade bans.[30] [31] Leading reproductive medicine experts, such as those from the American Society for Reproductive Medicine, rejected these as reckless and unscientific, noting high failure rates in animal cloning (e.g., over 90% embryonic loss) render human viability improbable without transparency.[32] No credible, verified instances of human reproductive cloning have occurred as of 2025, with major institutions like the National Human Genome Research Institute affirming such claims remain fictional amid persistent technical barriers like incomplete epigenetic reprogramming and elevated abnormality risks observed in mammalian clones.[1] Efforts by entities like Advanced Cell Technology in the early 2000s focused on therapeutic cloning of early-stage embryos (up to six cells) rather than viable births, yielding no reproductive outcomes.[33] Post-2010, public claims have dwindled, supplanted by advances in induced pluripotent stem cells and gene editing, though rogue assertions persist without empirical substantiation.[24]Scientific Methods and Techniques
Somatic Cell Nuclear Transfer
Somatic cell nuclear transfer (SCNT) is a cloning technique that involves transferring the nucleus of a somatic (non-reproductive) cell into an enucleated oocyte, or egg cell, to reprogram the donor nucleus and initiate embryonic development.[34] The process begins with isolating a mature oocyte from a donor female and removing its nucleus using micromanipulation tools, creating a cytoplast devoid of genetic material.[34] A somatic cell nucleus, typically from skin fibroblasts or other easily accessible tissues, is then inserted into the enucleated oocyte via electrofusion or microinjection.[34] Chemical or electrical activation follows to mimic fertilization, prompting the reconstructed embryo to divide and potentially form a blastocyst.[34] In therapeutic cloning applications, the SCNT-derived blastocyst is used to generate patient-matched embryonic stem cells, which can differentiate into various cell types without triggering immune rejection.[35] The first derivation of human embryonic stem cells via SCNT occurred in 2013, when researchers used fetal somatic cells and oocytes from eight donors, achieving a 10% blastocyst formation rate from 104 reconstructed embryos.[35] For reproductive cloning, the embryo is implanted into a surrogate uterus to develop into a full organism genetically identical to the somatic cell donor, though no verified human successes exist.[36] SCNT efficiency remains low due to incomplete epigenetic reprogramming, where the somatic nucleus fails to fully reset to an embryonic state, leading to aberrant gene expression and developmental arrest.[37] In animal models, live birth rates range from 1-5% of transferred embryos, with higher rates up to 20% in optimized bovine protocols using specific donor cell types.[36] Common abnormalities include large offspring syndrome, placental defects, and premature aging, attributed to persistent DNA methylation errors.[34] Human applications face additional hurdles, such as limited oocyte availability and ethical restrictions, restricting progress to therapeutic contexts.[38] Advances in reprogramming factors, like histone deacetylase inhibitors, have incrementally improved blastocyst yields in primates, but full-term viability in humans remains unachieved.[37]Stem Cell Reprogramming and Alternatives
Induced pluripotent stem cells (iPSCs) represent a primary alternative to somatic cell nuclear transfer (SCNT) for generating pluripotent cells suitable for therapeutic cloning applications. In 2006, Shinya Yamanaka and colleagues demonstrated that introducing four transcription factors—Oct4, Sox2, Klf4, and c-Myc—into mouse embryonic or adult fibroblasts could reprogram them into a pluripotent state resembling embryonic stem cells.[39] This breakthrough was extended to human cells in 2007, when the same factors successfully reprogrammed adult human dermal fibroblasts into iPSCs capable of forming teratomas and contributing to chimeric mice.[40] Unlike SCNT, which requires unfertilized oocytes and results in cloned embryos, iPSC generation uses readily available somatic cells from the patient, avoiding ethical concerns over embryo destruction and oocyte donation scarcity.[41] iPSCs enable the production of autologous pluripotent cells for disease modeling, drug screening, and regenerative therapies without nuclear transfer. These cells can differentiate into virtually any cell type, supporting applications like personalized medicine where patient-derived iPSCs are used to study genetic diseases or test treatments.[42] Advances since 2007 include non-integrating reprogramming methods, such as Sendai virus vectors or mRNA delivery, which reduce risks of genomic insertion mutations associated with early retroviral approaches.[42] By 2024, chemical reprogramming protocols—using small molecules to replace transcription factors—have improved efficiency and safety, though yields remain lower than viral methods at around 0.01-1% for human cells.[42] Despite these developments, iPSC technology faces biological limitations compared to SCNT-derived cells. Reprogrammed iPSCs often retain epigenetic memory from their somatic origin, leading to biased differentiation toward the donor cell type and incomplete maturation of derivatives, which hampers their use in modeling adult-onset diseases.[42] Tumorigenicity poses a major risk, as undifferentiated iPSCs or incompletely reprogrammed cells can form teratomas upon transplantation, with rates exceeding 20% in early mouse studies; human trials require rigorous purification to mitigate this.[43] Genetic aberrations, including copy number variations, accumulate during passaging, with mutation rates up to 10-20 per exome in long-term cultures, necessitating clonal selection and genomic screening.[44] Direct cellular reprogramming, or transdifferentiation, offers another alternative by converting somatic cells into specific lineages without passing through pluripotency, potentially sidestepping teratoma risks. For instance, fibroblasts have been directly reprogrammed into neurons or cardiomyocytes using lineage-specific transcription factors like Ascl1, Brn2, and Myt1l, achieving up to 20% efficiency in human cells by 2023.[45] This method preserves cell identity better than iPSCs but yields lineage-restricted cells unsuitable for broad therapeutic cloning goals. Hybrid approaches, such as combining iPSC technology with SCNT (iPSC-NT), have been explored to enhance reprogramming fidelity, producing cells with fewer epigenetic errors than either alone, though clinical translation remains preclinical as of 2025.[46] Overall, while iPSCs have largely supplanted SCNT in research due to accessibility, unresolved challenges in safety and fidelity limit their equivalence for human cloning applications.00445-4)Technical Comparisons and Limitations
Somatic cell nuclear transfer (SCNT) and induced pluripotent stem cell (iPSC) reprogramming represent primary techniques for generating patient-specific pluripotent cells, with SCNT involving the transfer of a somatic nucleus into an enucleated oocyte to initiate embryonic development, while iPSC generation reprograms somatic cells directly via transcription factors such as Oct4, Sox2, Klf4, and c-Myc without requiring oocytes.[37] SCNT leverages the oocyte's natural reprogramming machinery, potentially yielding more complete epigenetic erasure compared to iPSC methods, which rely on exogenous factors and exhibit persistent somatic epigenetic memory or heterogeneity.[37] However, iPSC reprogramming achieves higher initial efficiencies—often 0.01-1% for colony formation versus SCNT's embryo development rates below 5% in mammals—making it more scalable for therapeutic applications, though iPSCs carry risks of insertional mutagenesis from viral vectors or incomplete silencing of reprogramming factors.[42][47] In human contexts, SCNT has produced embryonic stem cell lines from adult fibroblasts, as demonstrated in 2013 with fetal cells and 2014 with adult dermal cells, confirming pluripotency and low immunogenicity for autologous use, but these efforts required hundreds of oocytes per line due to arrest at early cleavage stages.[48] iPSC methods, conversely, bypass oocyte dependency, enabling rapid derivation from accessible tissues like blood or skin, with human iPSC lines routinely generated since 2007 at efficiencies improved to over 1% via non-integrating vectors.[49] Yet, comparative genomic analyses reveal iPSCs accumulate more mutations and epigenetic aberrations than SCNT-derived cells, potentially limiting their fidelity for modeling or transplantation.[50] Key limitations of SCNT include profoundly low efficiency—typically 1-5% live birth rates in animal models like mice (around 2%) and pigs (1%), extrapolated to humans where no viable reproductive clones exist—and persistent epigenetic defects such as aberrant DNA methylation and histone modifications (e.g., H3K9me3 retention), causing developmental arrest, placental abnormalities, and post-natal syndromes like large offspring syndrome.[51][52][53] These stem from incomplete nuclear reprogramming, with somatic chromatin barriers resisting oocyte-mediated erasure, necessitating chemical inhibitors or donor age matching to modestly boost yields.[54] iPSC limitations encompass genetic instability from reprogramming-induced mutations (up to 10-20 per genome) and reduced differentiation potential due to bivalent domains or residual transgene expression, though these are mitigated in SCNT-iPSC hybrids that combine efficiencies.[42][46] Overall, both methods falter in replicating natural fertilization's fidelity, with SCNT's oocyte scarcity and ethical barriers hindering human reproductive applications, while iPSCs offer practicality at the cost of epigenetic fidelity.[55][49]Empirical Achievements and Evidence
Animal Cloning Outcomes
The first mammal successfully cloned using somatic cell nuclear transfer (SCNT) was Dolly the sheep, born on July 5, 1996, to Scottish researchers at the Roslin Institute. Dolly developed progressive lung disease (ovine pulmonary adenocarcinoma) and arthritis, leading to euthanasia on February 14, 2003, at approximately 6.5 years of age—less than half the typical 11-12 year lifespan for her breed (Finn Dorset).[1] [56] Subsequent analyses of Dolly's telomeres indicated shortened lengths suggestive of accelerated cellular aging, though direct causation remains debated.[57] However, four cloned sheep produced later using similar adult fibroblast cells—Debbie, Denise, Dianna, and Daisy—exhibited normal metabolic and age-related health markers at 7-9 years of age, free from common geriatric conditions like hypertension or diabetes, challenging early concerns of universal premature senescence.[58] [59] SCNT cloning efficiency across species remains low, typically yielding 0-10 live births per 100 transferred embryos, with most failures occurring during embryonic development, implantation, or gestation due to incomplete nuclear reprogramming and epigenetic errors.[34] In ruminants like cattle and sheep, large offspring syndrome (LOS)—characterized by fetal overgrowth, macrosomia, placental abnormalities, and hydroallantois—occurs in a significant proportion of pregnancies, increasing risks of dystocia, respiratory distress, and neonatal mortality.[60] [61] Cloned fetuses often display abnormal organ development, immune deficiencies, and cardiovascular issues, with post-birth survival rates under 5% in early bovine trials.[62] These outcomes stem from faulty gene expression patterns persisting from the donor somatic cell, leading to disrupted imprinting and mitochondrial incompatibilities.[54] Outcomes vary by species but consistently involve high procedural losses. In cattle, cloned since 1998, thousands have been produced for agricultural traits, yet many exhibit LOS-related defects or die perinatally; surviving clones and their offspring generally reach reproductive maturity without elevated disease incidence, per U.S. FDA assessments of 2008-2021 data.[63] Porcine clones, initiated in 2000, face similar placental and organ enlargement issues, with efficiency below 2% and frequent early deaths from heart failure or infections.[64] Mice, cloned via SCNT since 1998, achieve higher relative success (up to 5% in optimized protocols) but suffer high embryonic lethality and adult-onset tumors or obesity in some lines.[65] Dogs, with over 1,500 SCNT clones produced commercially by 2022 across ~20 breeds, demonstrate viable reproduction but incur substantial losses during gestation and neonate stages, mirroring ruminant patterns.[66] Other species, including cats (2001 onward), horses, and rabbits, report comparable inefficiencies and health anomalies, though long-term data indicate many healthy adults when gestation completes successfully.[1] Overall, while clones can thrive, the process's empirical toll—encompassing 90-99% failure rates and welfare impairments—highlights persistent biological barriers to reliable replication.[67]Human Therapeutic Cloning Advances
In 2013, researchers led by Shoukhrat Mitalipov at Oregon Health & Science University achieved the first successful derivation of human embryonic stem cell (hESC) lines using somatic cell nuclear transfer (SCNT). The team transferred nuclei from human fetal fibroblasts into enucleated oocytes, resulting in the development of blastocysts from which pluripotent hESC lines were isolated; these cells demonstrated normal karyotypes and pluripotency markers comparable to those from fertilized embryos.00571-0) This breakthrough followed optimizations from prior primate SCNT work, addressing previous inefficiencies in human attempts, such as incomplete reprogramming and developmental arrest.[68] Subsequent advances in 2014 involved deriving hESC lines from adult human somatic cells. Independent teams at the New York Stem Cell Foundation, led by Dieter Egli, and in South Korea successfully cloned embryos using adult cumulus cells via refined SCNT protocols, including caffeine treatment to prevent premature activation and histone deacetylase inhibitors to enhance reprogramming. These efforts yielded viable hESC lines genetically identical to the donors, confirming the technique's applicability to adult cells without relying on fetal sources.[69] Despite these milestones, therapeutic cloning via SCNT has not progressed to clinical applications in humans. As of 2020, no human embryos have been produced through SCNT for therapeutic purposes leading to treatments, with research limited by low efficiency rates—often below 5% blastocyst formation—and ethical restrictions on oocyte sourcing. Induced pluripotent stem cells (iPSCs) have largely supplanted SCNT in regenerative medicine due to avoiding embryo creation, though SCNT-derived hESCs offer advantages in mitochondrial compatibility for certain mitochondrial diseases.[1] Ongoing refinements focus on improving yield and safety, but empirical evidence of therapeutic efficacy remains preclinical.[37]Reproductive Cloning Status
No verified instances of successful human reproductive cloning, defined as the production of a genetically identical human via somatic cell nuclear transfer (SCNT) leading to live birth, have occurred as of 2025.[18] Scientific consensus holds that while cloned human embryos have been created in laboratory settings, none have progressed to viable pregnancies or births due to profound technical challenges and ethical prohibitions.[1] Early claims, such as those by Clonaid in 2002 announcing the birth of a cloned infant named "Eve," lacked independent verification and were dismissed by experts as unsubstantiated, with no DNA evidence provided despite demands.[70] Subsequent attempts, including announcements by figures like Severino Antinori in the early 2000s, failed to produce confirmed results, often ending in embryo transfer without pregnancy confirmation or retraction of claims.[71] In animals, SCNT yields low success rates—typically under 5% live births—with cloned offspring exhibiting high incidences of abnormalities like large offspring syndrome, immune deficiencies, and premature aging, patterns expected to amplify in humans given physiological complexities. Human embryo cloning experiments, such as those reported in 2001 by Advanced Cell Technology reaching four-to-six cell stages, halted short of implantation due to inefficiency and developmental arrest.[6] Legally, reproductive cloning faces near-universal bans, with approximately 46 countries enacting explicit prohibitions, including penalties up to 20 years imprisonment in France as reinforced in 2025.[72][9] International bodies like UNESCO advocate against it, citing risks to human dignity and safety, while bodies such as the U.S. President's Council on Bioethics have recommended indefinite federal bans.[17] These restrictions, coupled with institutional review board oversight and funding limitations, preclude sanctioned research, rendering practical advancement improbable absent regulatory shifts. Despite theoretical feasibility post-2013 embryo cloning demonstrations, no credible post-2020 efforts toward birth have surfaced, underscoring persistent viability barriers over sensational unverified assertions.[24][73]Potential Benefits and Applications
Medical and Therapeutic Prospects
Therapeutic cloning, primarily through somatic cell nuclear transfer (SCNT), enables the creation of patient-specific embryonic stem cells by replacing the nucleus of an enucleated oocyte with a somatic cell from the patient, followed by activation to form a blastocyst from which stem cells are derived.[74] These cells are genetically identical to the donor, minimizing immune rejection risks in regenerative therapies without requiring lifelong immunosuppression.[75] Potential applications include generating dopaminergic neurons for Parkinson's disease, where animal models using SCNT-derived cells have shown functional restoration of motor deficits.[37] In diabetes treatment, SCNT could produce insulin-secreting beta cells tailored to the patient, addressing the autoimmune destruction of pancreatic islets in type 1 diabetes; preclinical studies in non-human primates demonstrate viability of such approaches for personalized islet transplantation.[76] For spinal cord injuries and myocardial infarction, cloned stem cells might differentiate into neural or cardiac tissue, promoting repair; early human SCNT lines established in 2014 confirmed pluripotency and normal karyotypes, supporting feasibility for tissue engineering.[48] Additionally, these cells facilitate disease modeling and drug screening, accelerating personalized medicine by replicating patient-specific pathologies in vitro.[77] Beyond direct cell replacement, therapeutic cloning prospects extend to organ regeneration, such as bioengineered kidneys or livers from cloned progenitors, potentially alleviating transplant shortages; while human applications remain experimental, successes in cloning porcine organs for xenotransplantation hint at scalable therapeutic paradigms.[78] Integration with genome editing, like CRISPR, could correct underlying genetic defects prior to differentiation, enhancing outcomes for monogenic disorders such as cystic fibrosis or sickle cell anemia.[37] Despite technical hurdles like low efficiency—typically under 5% in mammalian SCNT—these methods offer causal advantages in histocompatibility over allogeneic sources, positioning therapeutic cloning as a cornerstone for future autologous therapies.[51]Reproductive and Personal Uses
Reproductive cloning involves the creation of a genetically identical human embryo via somatic cell nuclear transfer (SCNT), with the intent to implant it for gestation to term, resulting in a live birth of a cloned individual.[1] This differs from therapeutic cloning by aiming for full human development rather than tissue or organ production. Proponents argue it could enable infertile individuals or couples to produce offspring genetically related to one parent, bypassing limitations of gamete donation or surrogacy where full genetic identity to both is impossible.[79] For instance, a couple where one partner has gamete failure could clone the fertile partner's cells to generate an embryo sharing that parent's full genome, though mitochondrial DNA from the egg donor would introduce minor non-nuclear variation.[2] Personal motivations for reproductive cloning often center on preserving individual genetics across generations or mitigating personal loss. Some envision cloning deceased relatives—such as a child lost to accident or disease—to create a genetically identical sibling, allowing families to "continue" a lineage or grieve through a biological facsimile.[1] Self-cloning has been hypothesized for extending personal legacy, where an individual produces a genetic twin raised in a controlled environment to inherit specific traits or knowledge, though environmental factors like epigenetics and upbringing would prevent true identity replication.[3] Advocates, including bioethicists like Julian Savulescu, contend such applications could fulfill autonomous reproductive rights, akin to existing assisted reproduction technologies, provided safety thresholds are met.[12] Despite these rationales, no verified human reproductive cloning has succeeded as of 2025, with historical claims—such as the 2002 announcement by Clonaid of a cloned infant named Eve—lacking empirical evidence and dismissed by scientific consensus due to absence of genetic verification or peer-reviewed data.[1] Animal models, including Dolly the sheep cloned in 1996, demonstrate feasibility in principle but highlight inefficiencies: success rates below 5% in mammals, with frequent developmental anomalies like large offspring syndrome and premature aging.[80] These empirical hurdles render personal uses speculative, as human gestation lacks the optimizations possible in veterinary cloning, and unverified attempts risk unquantified health defects in clones.[8] Nonetheless, theoretical personal benefits persist in discourse, such as generating immunologically matched siblings for tissue compatibility in families with rare genetic disorders, extending beyond mere reproduction to targeted familial health strategies.[79]Risks and Empirical Challenges
Biological and Health Hazards
Reproductive cloning via somatic cell nuclear transfer (SCNT) in mammals exhibits profound inefficiencies, with success rates typically below 5%, often requiring hundreds of attempts to produce a viable offspring, as evidenced by the 277 nuclear transfer procedures needed for Dolly the sheep in 1996.[1] This stems from incomplete epigenetic reprogramming of the donor somatic nucleus, leading to aberrant gene expression, disrupted genomic imprinting, and high rates of embryonic lethality or fetal loss.[81] In surviving clones, common outcomes include large offspring syndrome (LOS), characterized by oversized fetuses, placental overgrowth, and cardiovascular strain, which contributes to dystocia and neonatal mortality exceeding 90% in some species like cattle and sheep.[82] Cloned animals frequently suffer organ malformations, immune deficiencies, and metabolic disorders due to these reprogramming failures, with studies in bovine clones reporting elevated incidences of hepatic steatosis, renal dysplasia, and pulmonary hypertension.[3] Long-term health concerns involve potential premature aging linked to telomere attrition, as somatic donor cells carry shortened telomeres from prior divisions, though telomerase reactivation in embryos can partially restore length; however, one-third to half of cloned cohorts show persistent reductions compared to age-matched controls, correlating with accelerated senescence in tissues.[83] While some cloned sheep derived from Dolly's cell line reached ages of 9 years without overt aging deficits, earlier cases like Dolly's euthanasia at age 6 due to progressive lung disease and osteoarthritis fueled debates over cloning-induced vulnerabilities, underscoring unresolved risks of stochastic epigenetic errors.[84] [58] In human therapeutic cloning, SCNT-derived embryos for stem cell production face analogous hazards, including chromosomal instability and oncogenic transformations from faulty reprogramming, with animal models indicating heightened tumor formation risks in derived tissues.[85] Mitochondrial heteroplasmy—carryover of donor oocyte mitochondria mismatched with the nuclear genome—poses additional threats, potentially triggering immune-mediated rejection even in autologous transplants, as demonstrated in murine studies where mitochondrial antigens elicited T-cell responses leading to graft failure.[86] These biological imperatives, rooted in the causal mismatches between differentiated donor nuclei and embryonic contexts, render human cloning hazardous without technological breakthroughs to mitigate pervasive developmental and oncogenic perils.[11]Efficiency and Viability Issues
Somatic cell nuclear transfer (SCNT), the primary technique for human cloning, exhibits extremely low efficiency in mammalian species, with live birth rates typically ranging from 1% to 5% of transferred embryos in animals such as mice, sheep, and cattle.[51] This inefficiency arises from incomplete epigenetic reprogramming of the donor nucleus, leading to failures in gene expression and developmental arrest at early embryonic stages.[34] In sheep cloning, blastocyst formation rates reach 5.3% to 42%, but progression to viable newborns occurs in only 5.7% to 15% of transferred embryos, underscoring persistent technical barriers.[87] For prospective human reproductive cloning, these animal outcomes indicate profound viability challenges, as no verified live births have occurred despite claims, with efficiency likely even lower due to human oocyte scarcity and heightened ethical constraints on experimentation.[1] Cloned animals frequently suffer from severe health defects, including large offspring syndrome characterized by oversized fetuses, placental abnormalities, and respiratory distress, contributing to high perinatal mortality rates—up to 42% in cloned calves within the first 150 days.[88][82] Epigenetic errors, such as improper DNA methylation and histone modifications, causally underlie these issues, resulting in organ dysfunction, immune deficiencies, and accelerated aging in survivors.[89] Therapeutic cloning via SCNT for human embryonic stem cell derivation faces analogous hurdles, with blastocyst development rates historically below 10% and derivation of viable stem cell lines rare until isolated advances, such as the 2013 production of human nuclear transfer embryonic stem cells from adult fibroblasts at efficiencies not exceeding a few percent.[90][91] While some cloned animals, like dogs and sheep, show no evident long-term health deficits post-survival, the overall process demands hundreds of oocyte donations and embryo transfers per success, rendering it economically and biologically unviable for routine application without major reprogramming breakthroughs.[66][92] These empirical limitations highlight SCNT's fundamental constraints in achieving reliable nuclear totipotency.[93]Ethical and Philosophical Debates
Arguments in Favor of Cloning
Proponents of human reproductive cloning contend that it could enable infertile individuals or couples to have genetically related offspring, extending reproductive technologies beyond gamete donation or surrogacy to produce a child with one parent's nuclear DNA.[94] This approach has been proposed as a means to fulfill the desire for biological continuity in cases where traditional conception fails due to sterility or gamete scarcity, akin to how in vitro fertilization addressed prior barriers.[79] Another argument posits that cloning offers a way to mitigate certain inherited genetic disorders by replicating the genome of a healthy parent, thereby avoiding the recombination risks in sexual reproduction that can propagate recessive lethal alleles. For instance, if both parents carry a single copy of a recessive disease gene, natural procreation yields a 25% chance of an affected child, whereas cloning the unaffected parent's genome eliminates this probability.[95] Advocates emphasize that this method preserves familial genetic lineage without introducing foreign donor DNA, potentially reducing the incidence of conditions like cystic fibrosis or Tay-Sachs disease in high-risk pedigrees.[96] Cloning has also been advocated to recreate a deceased loved one, such as a child lost to accident or illness, providing parents an opportunity to raise a genetic duplicate and thereby alleviate profound grief through renewed parental bonds.[96] This perspective frames cloning not as identical resurrection but as a biological proxy that honors the original's genome while allowing for environmental influences to shape a distinct individual.[94] From a utilitarian standpoint, some scholars suggest human cloning could enhance human capabilities by duplicating genomes associated with exceptional health, intelligence, or achievement, thereby accelerating societal progress without relying solely on random genetic variation.[12] This includes selecting for traits like disease resistance or cognitive prowess, which proponents argue would yield net benefits in population-level fitness if technical efficiencies improve beyond current animal cloning success rates of under 5% viable births.[97] Such applications are viewed as extensions of selective breeding principles observed in agriculture and animal husbandry, applied ethically to voluntary human enhancement.[12]Arguments Against Cloning
Opponents of human cloning, particularly reproductive cloning, argue that it undermines human dignity by treating individuals as manufactured copies rather than unique beings arising from natural procreation. The United Nations General Assembly's 2005 Declaration on Human Cloning urged member states to prohibit all forms of human cloning, deeming them incompatible with human dignity and the protection of human life.[98] This position reflects concerns that cloning instrumentalizes human life, reducing persons to genetic replicas for parental or societal purposes, thereby eroding the intrinsic value of individuality.[17] Empirical data from animal cloning underscores profound biological risks, including high rates of embryonic failure, gestational abnormalities, and post-birth health defects, which would likely translate to human attempts. Reproductive cloning in mammals is inefficient, with success rates below 5% in species like sheep and cattle; for instance, Dolly the sheep required 277 nuclear transfer attempts, and most cloned embryos fail to implant or develop normally. Surviving clones often exhibit large offspring syndrome, organ enlargement, immune deficiencies, and premature aging due to incomplete epigenetic reprogramming, as evidenced by shortened telomeres and elevated disease incidence in bovine and ovine clones.[99] Dolly developed arthritis at age 5—unusual for her breed—and was euthanized at 6.5 years due to progressive lung disease, prompting early concerns about accelerated aging in clones, though subsequent clones from the same cell line showed no such anomalies, indicating persistent technical uncertainties rather than resolved risks.[100] Such biological hazards extend to surrogate mothers, who face elevated risks of miscarriage, placental abnormalities, and complications from oversized fetuses, as documented in cloned animal pregnancies with abortion rates exceeding 50%.[61] The National Academy of Sciences has warned that human reproductive cloning would inevitably produce suffering through trial-and-error iterations, with many clones dying in utero or shortly after birth, and survivors prone to unforeseen pathologies absent in natural reproduction.[101] Social and psychological arguments highlight potential harms to cloned individuals, including identity crises from predetermined genetic origins and societal perceptions of them as replacements or experiments, akin to but exceeding challenges faced by twins.[79] Clones may experience reduced autonomy if viewed through the lens of their progenitor's expectations, fostering psychological distress or exploitation, as ethicists contend that replication denies the open-endedness of human development.[12] Broader societal risks include exacerbating inequalities, as cloning access would favor the wealthy, potentially leading to a stratified class of "designer" humans and reinforcing eugenic pressures without addressing underlying genetic diversities that confer resilience.[95] These concerns, grounded in observed animal outcomes and philosophical analysis of personhood, substantiate calls for indefinite prohibition to avert irreversible ethical and empirical pitfalls.Debunking Prevalent Misconceptions
A prevalent misconception holds that human reproductive cloning has already been successfully achieved, often fueled by unsubstantiated claims such as those from the Clonaid organization in 2002, which announced the birth of a cloned infant named "Eve" without providing verifiable evidence or allowing independent verification. No peer-reviewed scientific confirmation of a live-born human clone via somatic cell nuclear transfer exists, and experts attribute the absence of verified successes to persistent technical barriers, including low implantation rates and high embryonic loss observed in mammalian cloning experiments.[24][3] Another widespread myth posits that clones would be exact replicas of the donor in every respect, including physical appearance, personality, and aging trajectory, akin to a photocopy. In reality, while nuclear DNA would match the somatic cell donor, mitochondrial DNA derives from the egg donor, introducing genetic variation; moreover, epigenetic modifications, environmental influences, and stochastic developmental events produce differences comparable to those between identical twins raised apart. Cloned animals exhibit phenotypic variations from their donors, underscoring that cloning replicates genetic starting material but not life experiences or non-genetic factors.[102][103] Concerns about premature aging in clones stem largely from Dolly the sheep's early death in 2003 at age 6.5 years from a lung infection, compounded by her shortened telomeres and arthritis, which prompted fears of inherent replicative senescence in clones. However, a 2016 study of four sheep cloned from the same cell line as Dolly revealed normal lifespans of 7 to 9.3 years with no unanticipated health deficits, and telomere restoration techniques, such as telomerase activation, have yielded clones with telomere lengths equivalent to age-matched controls. Dolly's joint wear was later deemed comparable to non-clones of similar breed and obesity, indicating her issues were not uniquely attributable to cloning. Ongoing refinements in nuclear transfer protocols have reduced such anomalies, with many cloned mammals achieving health outcomes indistinguishable from conventionally bred counterparts.[92][104][105] The belief that cloning is a straightforward, high-yield process ignores empirical data from animal trials, where success rates remain below 5-10% for live births, often involving hundreds of reconstructed embryos, frequent miscarriages, and neonatal defects like large offspring syndrome. Techniques have improved since Dolly's 1996 creation—achieved after 277 attempts—but human applications face amplified challenges due to protracted gestation and ethical constraints on large-scale trials, rendering current claims of feasibility overstated.[106][107]Legal and Regulatory Frameworks
International Positions
International regulatory efforts on human cloning have produced non-binding declarations and limited regional protocols, with no comprehensive global treaty in force. The United Nations General Assembly adopted the United Nations Declaration on Human Cloning on March 8, 2005, calling on member states to prohibit all forms of human cloning on grounds that such practices are incompatible with human dignity and the protection of human life in its dignity and integrity. The resolution passed by a vote of 84 in favor, 34 against, and 37 abstentions, highlighting divisions particularly over therapeutic applications of cloning techniques for biomedical research.[98][108] The Council of Europe established the first multilateral instrument specifically targeting cloning through the Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, opened for signature on January 12, 1998. Article 1 of the protocol states: "Any intervention seeking to create a human being genetically identical to another human being, whether living or dead, is prohibited," applying to interventions performed in the signatory state or by its nationals abroad. Ratified by 23 countries as of 2023, the protocol emphasizes reproductive cloning but leaves therapeutic uses unaddressed, serving as a model for national legislation in Europe.[109] UNESCO's Universal Declaration on the Human Genome and Human Rights, adopted by the General Conference on November 11, 1997, declares that "practices which are contrary to human dignity, such as reproductive cloning of human beings, shall not be permitted," underscoring the need for international bioethical standards to safeguard genomic integrity. Subsequent UNESCO reports, including those from the International Bioethics Committee, have reinforced opposition to reproductive cloning while advocating for governance frameworks that distinguish it from research-oriented somatic cell nuclear transfer.[110][111] The World Health Organization has consistently advised against human reproductive cloning, citing empirical evidence from animal studies showing high rates of developmental abnormalities, implantation failures, and health risks in clones, such as large offspring syndrome and premature aging. In a 2004 report to the Executive Board, WHO noted the absence of safe, verified techniques for human application and recommended global vigilance without endorsing prohibitions on therapeutic cloning for stem cell research. These positions reflect a consensus against reproductive cloning due to verifiable biological hazards, though enforcement remains dependent on national laws amid varying interpretations of dignity and scientific utility.[112]Domestic Laws by Jurisdiction
Domestic laws on human cloning predominantly prohibit reproductive cloning, aimed at producing a cloned human being, while therapeutic cloning—for deriving embryonic stem cells—receives more varied treatment, with permissions in some nations under strict oversight. Over 46 countries have enacted formal bans on reproductive cloning, though enforcement and scope differ.[9] Bans typically criminalize the transfer of a cloned embryo to a uterus, with penalties including imprisonment. In the United States, no federal statute explicitly prohibits human reproductive cloning, leaving it unregulated at the national level beyond restrictions on federal funding for cloning research.[113] Several states have imposed bans: California, Iowa, Louisiana, Michigan, Rhode Island, and Virginia prohibit both reproductive and therapeutic cloning, while others like Arizona and Florida ban only reproductive efforts.[114] Therapeutic cloning remains permissible in states without specific prohibitions, subject to institutional review boards and ethical guidelines from bodies like the National Academies.[113] Canada's Assisted Human Reproduction Act of 2004 explicitly bans human cloning, including the creation of cloned embryos for any purpose, with penalties up to 10 years imprisonment and fines.[115] This encompasses both reproductive and therapeutic applications, prohibiting embryo cloning for stem cell derivation.[9] In the United Kingdom, the Human Reproductive Cloning Act 2001 criminalizes reproductive cloning, making it an offense to place a cloned embryo in a woman, punishable by up to 10 years in prison.[116] Therapeutic cloning is permitted under licenses from the Human Fertilisation and Embryology Authority, allowing somatic cell nuclear transfer for research but not implantation.[117] Australia's Prohibition of Human Cloning for Reproduction Act 2002 bans reproductive cloning nationwide, with 15-year prison terms for violations, and also prohibits therapeutic cloning involving embryo creation for research beyond 14 days.[118] States like Victoria permit certain stem cell research but align with federal bans on cloning.[115] Japan's 2001 guidelines, updated in subsequent laws, prohibit human reproductive cloning as unethical, with criminal penalties, but authorize therapeutic cloning for medical research under the Ministry of Education, Culture, Sports, Science and Technology oversight.[119] China bans reproductive cloning through regulations from the Ministry of Science and Technology, emphasizing ethical guidelines post-2004, but permits therapeutic cloning and embryo research for biomedical purposes, as seen in approvals for stem cell derivation.[70][120] Across European Union member states, reproductive cloning is uniformly prohibited under national bioethics laws, often aligned with the Council of Europe's 1998 Oviedo Protocol, ratified by 23 nations, which bans any cloning creating human beings.[121] France's 2025 bioethics law reinforces a ban on reproductive cloning with up to 20 years imprisonment, while therapeutic cloning remains restricted.[72] Germany and Austria extend bans to all forms of cloning, including therapeutic embryo creation. Variations persist, with some like Belgium allowing limited therapeutic research.[9]| Jurisdiction | Reproductive Cloning | Therapeutic Cloning | Key Legislation |
|---|---|---|---|
| United States (Federal) | Not banned | Funding restricted; state variations | No comprehensive federal law[113] |
| Canada | Banned | Banned | Assisted Human Reproduction Act 2004[115] |
| United Kingdom | Banned | Permitted with license | Human Reproductive Cloning Act 2001[116] |
| Australia | Banned | Restricted (no embryo >14 days) | Prohibition of Human Cloning Act 2002[118] |
| Japan | Banned | Permitted | 2001 Guidelines |
| China | Banned | Permitted for research | Ministry Regulations 2004[70] |
| France | Banned (20 years max) | Restricted | Bioethics Law 2025[72] |
| Germany | Banned (all forms) | Banned | Embryo Protection Act |