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Human cloning is the creation of a genetically identical copy of a human. The term is generally used to refer to artificial human
cloning Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...
, which is the reproduction of human cells and tissue. It does not refer to the natural conception and delivery of identical
twins Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of Twin Last Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two e ...
. The possibilities of human cloning have raised controversies. These ethical concerns have prompted several nations to pass laws regarding human cloning. Two commonly discussed types of human cloning are ''therapeutic cloning'' and ''reproductive cloning''. Therapeutic cloning would involve cloning cells from a human for use in medicine and transplants. It is an active area of research, and is in medical practice over the world. Two common methods of therapeutic cloning that are being researched are
somatic-cell nuclear transfer In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a Somatic cell, body cell and an egg cell. The technique consists of taking a denucleated oocyte (egg cell) ...
and (more recently) pluripotent stem cell induction. Reproductive cloning would involve making an entire cloned human, instead of just specific cells or tissues.


History

Although the possibility of
cloning Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...
humans had been the subject of speculation for much of the 20th century, scientists and policymakers began to take the prospect seriously in 1969. J. B. S. Haldane was the first to introduce the idea of human cloning, for which he used the terms "clone" and "cloning", which had been used in agriculture since the early 20th century. In his speech on "Biological Possibilities for the Human Species of the Next Ten Thousand Years" at the '' Ciba Foundation Symposium on Man and his Future'' in 1963, he said: Nobel Prize-winning geneticist
Joshua Lederberg Joshua Lederberg (May 23, 1925 – February 2, 2008) was an American molecular biology, molecular biologist known for his work in microbial genetics, artificial intelligence, and the United States space program. He was 33 years old when he won t ...
advocated cloning and
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of Genetic engineering techniques, technologies used to change the genet ...
in an article in '' The American Naturalist'' in 1966 and again, the following year, in ''
The Washington Post ''The Washington Post'', locally known as ''The'' ''Post'' and, informally, ''WaPo'' or ''WP'', is an American daily newspaper published in Washington, D.C., the national capital. It is the most widely circulated newspaper in the Washington m ...
''. He sparked a debate with conservative bioethicist Leon Kass, who wrote at the time that "the programmed reproduction of man will, in fact, dehumanize him." Another
Nobel Laureate The Nobel Prizes (, ) are awarded annually by the Royal Swedish Academy of Sciences, the Swedish Academy, the Karolinska Institutet, and the Norwegian Nobel Committee to individuals and organizations who make outstanding contributions in th ...
, James D. Watson, publicized the potential and the perils of cloning in his ''
Atlantic Monthly ''The Atlantic'' is an American magazine and multi-platform publisher based in Washington, D.C. It features articles on politics, foreign affairs, business and the economy, culture and the arts, technology, and science. It was founded in 1857 ...
'' essay, "Moving Toward the Clonal Man", in 1971. With the cloning of a sheep known as Dolly in 1996 by
somatic cell nuclear transfer In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking a denucleated oocyte (egg cell) and implanti ...
(SCNT), the idea of human cloning became a hot debate topic. Many nations outlawed it, while a few scientists promised to make a clone within the next few years. The first hybrid human clone was created in November 1998, by Advanced Cell Technology. It was created using SCNT; a nucleus was taken from a man's leg cell and inserted into a cow's egg from which the nucleus had been removed, and the hybrid cell was cultured and developed into an
embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...
. The embryo was destroyed after 12 days. In 2004 and 2005, Hwang Woo-suk, a professor at
Seoul National University Seoul National University (SNU; ) is a public university, public research university in Seoul, South Korea. It is one of the SKY (universities), SKY universities and a part of the Flagship Korean National Universities. The university's main c ...
, published two separate articles in the journal '' Science'' claiming to have successfully harvested pluripotent,
embryonic stem cells Embryonic stem cells (ESCs) are Cell potency#Pluripotency, pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-Implantation (human embryo), implantation embryo. Human embryos reach the blastocyst stage 4� ...
from a cloned human blastocyst using SCNT techniques. Hwang claimed to have created eleven different patient-specific stem cell lines. This would have been the first major breakthrough in human cloning. However, in 2006 ''Science'' retracted both of his articles on account of clear evidence that much of his data from the experiments was fabricated. In January 2008, Dr. Andrew French and Samuel Wood of the biotechnology company Stemagen announced that they successfully created the first five mature human embryos using SCNT. In this case, each embryo was created by taking a nucleus from a skin cell (donated by Wood and a colleague) and inserting it into a human egg from which the nucleus had been removed. The embryos were developed only to the
blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the ...
stage, at which point they were studied in processes that destroyed them. Members of the lab said that their next set of experiments would aim to generate embryonic stem cell lines; these are the "holy grail" that would be useful for therapeutic or reproductive cloning. In 2011, scientists at the New York Stem Cell Foundation announced that they had succeeded in generating embryonic stem cell lines, but their process involved leaving the
oocyte An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...
's nucleus in place, resulting in
triploid Polyploidy is a condition in which the cells of an organism have more than two paired sets of ( homologous) chromosomes. Most species whose cells have nuclei (eukaryotes) are diploid, meaning they have two complete sets of chromosomes, one fro ...
cells, which would not be useful for cloning. In 2013, a group of scientists led by Shoukhrat Mitalipov published the first report of embryonic stem cells created using SCNT. In this experiment, the researchers developed a protocol for using SCNT in human cells, which differs slightly from the one used in other organisms. Four embryonic stem cell lines from human fetal somatic cells were derived from those blastocysts. All four lines were derived using oocytes from the same donor, ensuring that all
mitochondrial DNA Mitochondrial DNA (mtDNA and mDNA) is the DNA located in the mitochondrion, mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the D ...
inherited was identical. A year later, a team led by Robert Lanza at Advanced Cell Technology reported that they had replicated Mitalipov's results and further demonstrated the effectiveness by cloning adult cells using SCNT. In 2018, the first successful
cloning Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...
of
primates Primates is an order of mammals, which is further divided into the strepsirrhines, which include lemurs, galagos, and lorisids; and the haplorhines, which include tarsiers and simians ( monkeys and apes). Primates arose 74–63  ...
using SCNT was reported with the birth of two live female clones, crab-eating macaques named Zhong Zhong and Hua Hua.


Methods


Somatic cell nuclear transfer (SCNT)

In somatic cell nuclear transfer ("SCNT"), the nucleus of a
somatic cell In cellular biology, a somatic cell (), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Somatic cells compose the body of an organism ...
is taken from a donor and transplanted into a host
egg cell The egg cell or ovum (: ova) is the female Reproduction, reproductive cell, or gamete, in most anisogamous organisms (organisms that reproduce sexually with a larger, female gamete and a smaller, male one). The term is used when the female game ...
, which had its own genetic material removed previously, making it an enucleated egg. After the donor somatic cell genetic material is transferred into the host oocyte with a micropipette, the somatic cell genetic material is fused with the egg using an electric current. Once the two cells have fused, the new cell can be permitted to grow in a surrogate or artificially. This is the process that was used to successfully clone Dolly the sheep (see ). The technique, now refined, has indicated that it was possible to replicate cells and reestablish pluripotency, or "the potential of an embryonic cell to grow into any one of the numerous different types of mature body cells that make up a complete organism".


Induced pluripotent stem cells (iPSCs)

Creating induced
pluripotent Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
s ("iPSCs") is a long and inefficient process.
Pluripotency Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...
refers to a stem cell that has the potential to differentiate into any of the three
germ layers A germ layer is a primary layer of cell (biology), cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce tw ...
:
endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gastr ...
(interior stomach lining, gastrointestinal tract, the lungs),
mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...
(muscle, bone, blood, urogenital), or
ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...
(epidermal tissues and nervous tissue). A specific set of genes, often called "reprogramming factors", are introduced into a specific adult cell type. These factors send
signals A signal is both the process and the result of Signal transmission, transmission of data over some transmission media, media accomplished by embedding some variation. Signals are important in multiple subject fields including signal processin ...
in the mature cell that cause the cell to become a pluripotent stem cell. This process is highly studied and new techniques are being discovered frequently on how to improve this induction process. Depending on the method used, reprogramming of adult cells into iPSCs for implantation could have severe limitations in humans. If a virus is used as a reprogramming factor for the cell, cancer-causing genes called
oncogenes An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
may be activated. These cells would appear as rapidly dividing cancer cells that do not respond to the body's natural cell signaling process. However, in 2008 scientists discovered a technique that could remove the presence of these oncogenes after pluripotency induction, thereby increasing the potential use of iPSC in humans.


Comparing SCNT to reprogramming

Both the processes of SCNT and iPSCs have benefits and deficiencies. Historically, reprogramming methods were better studied than SCNT derived embryonic stem cells (ESCs). However, more recent studies have put more emphasis on developing new procedures for SCNT-ESCs. The major advantage of SCNT over iPSCs at this time is the speed with which cells can be produced. iPSCs derivation takes several months while SCNT would take a much shorter time, which could be important for medical applications. New studies are working to improve the process of iPSC in terms of both speed and efficiency with the discovery of new reprogramming factors in oocytes. Another advantage SCNT could have over iPSCs is its potential to treat mitochondrial disease, as it uses a donor oocyte. No other advantages are known at this time in using stem cells derived from one method over stem cells derived from the other.


Uses and actual potential

Work on cloning techniques has advanced understanding of
developmental biology Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of Regeneration (biology), regeneration, asexual reproduction, metamorphosis, and the growth and di ...
in humans. Observing human pluripotent stem cells grown in culture provides great insight into human embryo development, which otherwise cannot be seen. Scientists are now able to better define steps of early human development. Studying
signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...
along with genetic manipulation within the early human embryo has the potential to provide answers to many developmental diseases and defects. Many human-specific signaling pathways have been discovered by studying human embryonic stem cells. Studying developmental pathways in humans has given developmental biologists more evidence toward the hypothesis that developmental pathways are conserved throughout species. iPSCs and cells created by SCNT are useful for research into the causes of disease, and as model systems used in
drug discovery In the fields of medicine, biotechnology, and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or ...
. Cells produced with SCNT, or iPSCs could eventually be used in stem cell therapy, or to create organs to be used in transplantation, known as
regenerative medicine Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by st ...
. Stem cell therapy is the use of stem cells to treat or prevent a disease or condition.
Bone marrow transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce a ...
is a widely used form of stem cell therapy. No other forms of stem cell therapy are in clinical use at this time. Research is underway to potentially use stem cell therapy to treat
heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
,
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
, and
spinal cord injuries A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. It is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Symptoms of ...
.Cell Basics: What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized?
. In Stem Cell Information World Wide Web site. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2009. cited Sunday, 26 April 2009
Regenerative medicine is not in clinical practice, but is heavily researched for its potential uses. This type of medicine would allow for autologous transplantation, thus removing the risk of organ transplant rejection by the recipient. For instance, a person with liver disease could potentially have a new liver grown using their same genetic material and transplanted to remove the damaged liver. In current research, human pluripotent stem cells have been promised as a reliable source for generating human neurons, showing the potential for regenerative medicine in brain and neural injuries.


Ethical implications

In
bioethics Bioethics is both a field of study and professional practice, interested in ethical issues related to health (primarily focused on the human, but also increasingly includes animal ethics), including those emerging from advances in biology, me ...
, the ethics of cloning refers to a variety of ethical positions regarding the practice and possibilities of
cloning Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...
, especially human cloning. While many of these views are religious in origin, for instance relating to Christian views of procreation and personhood, the questions raised by cloning engage secular perspectives as well, particularly the concept of identity. Advocates support development of therapeutic cloning in order to generate tissues and whole organs to treat patients who otherwise cannot obtain transplants, to avoid the need for
immunosuppressive drugs Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...
, and to stave off the effects of aging. Advocates for reproductive cloning believe that parents who cannot otherwise procreate should have access to the technology. Opposition to therapeutic cloning mainly centers around the status of
embryonic stem cells Embryonic stem cells (ESCs) are Cell potency#Pluripotency, pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-Implantation (human embryo), implantation embryo. Human embryos reach the blastocyst stage 4� ...
, which has connections with the
abortion debate The abortion debate is a longstanding and contentious discourse that touches on the moral, legal, medical, and religious aspects of induced abortion. In English-speaking countries, the debate has two major sides, commonly referred to as the "pro- ...
. The moral argument put forward is based on the notion that embryos deserve protection from the moment of their conception because it is at this precise moment that a new human entity emerges, already a unique individual. Since it is deemed unacceptable to sacrifice human lives for any purpose, the argument asserts that the destruction of embryos for research purposes is no longer justifiable. Some opponents of reproductive cloning have concerns that technology is not yet developed enough to be safe – for example, the position of the
American Association for the Advancement of Science The American Association for the Advancement of Science (AAAS) is a United States–based international nonprofit with the stated mission of promoting cooperation among scientists, defending scientific freedom, encouraging scientific responsib ...
while others emphasize that reproductive cloning could be prone to abuse (leading to the generation of humans whose organs and tissues would be harvested), and have concerns about how cloned individuals could integrate with families and with society at large. Members of religious groups are divided. Some Christian theologians perceive the technology as usurping God's role in creation and, to the extent embryos are used, destroying a human life; others see no inconsistency between Christian tenets and cloning's positive and potentially life-saving benefits.


Legal status of human therapeutic cloning maps


Legal status of human cloning by jurisdiction


Legal status of human cloning by

U.S. state In the United States, a state is a constituent political entity, of which there are 50. Bound together in a political union, each state holds governmental jurisdiction over a separate and defined geographic territory where it shares its so ...


In popular culture

Science fiction has used cloning, most commonly and specifically human cloning, due to the fact that it brings up controversial questions of identity. Humorous fiction, such as '' Multiplicity'' (1996) and the Maxwell Smart feature ''
The Nude Bomb ''The Nude Bomb'' (also known as ''The Return of Maxwell Smart'') is a 1980 American spy comedy film based on the 1965–70 television series ''Get Smart''. It stars Don Adams as Maxwell Smart, Agent 86, and was directed by Clive Donner. It ...
'' (1980), have featured human cloning. A recurring sub-theme of cloning fiction is the use of clones as a supply of organs for transplantation. Robin Cook's 1997 novel '' Chromosome 6'', Michael Bay's '' The Island'', and Nancy Farmer's 2002 novel ''House of the Scorpion'' are examples of this; ''Chromosome 6'' also features
genetic manipulation Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including th ...
and xenotransplantation. The ''
Star Wars ''Star Wars'' is an American epic film, epic space opera media franchise created by George Lucas, which began with the Star Wars (film), eponymous 1977 film and Cultural impact of Star Wars, quickly became a worldwide popular culture, pop cu ...
'' saga makes use of millions of human clones to form the
Grand Army of the Republic The Grand Army of the Republic (GAR) was a fraternal organization composed of veterans of the Union Army (United States Army), Union Navy (United States Navy, U.S. Navy), and the United States Marine Corps, Marines who served in the American Ci ...
that participated in the Clone Wars. The series ''
Orphan Black ''Orphan Black'' is a Canadian science-fiction thriller television series created by screenwriter Graeme Manson and director John Fawcett and starring Tatiana Maslany. The series focuses on Sarah Manning, one of several genetically identica ...
'' follows human clones' stories and experiences as they deal with issues and react to being the property of a chain of scientific institutions. In the 2019 horror film '' Us'', the entirety of the United States' population is secretly cloned. Years later, these clones (known as The Tethered) reveal themselves to the world by successfully pulling off a mass genocide of their counterparts. In the 2005 novel '' Never Let Me Go'',
Kazuo Ishiguro is a Japanese-born English novelist, screenwriter, musician, and short-story writer. He is one of the most critically acclaimed contemporary fiction authors writing in English, having been awarded several major literary prizes, including the 2 ...
crafts a subtle exploration into the ethical complications of cloning humans for medical advancement and longevity.


See also

*
Homunculus A homunculus ( , , ; "little person", : homunculi , , ) is a small human being. Popularized in 16th-century alchemy and 19th-century fiction, it has historically referred to the creation of a miniature, fully formed human. The concept has root ...
* Hwang affair


Notes and references


Notes


References


Further reading

* Araujo, Robert John, "The UN Declaration on Human Cloning: a survey and assessment of the debate," 7 The National Catholic Bioethics Quarterly 129 – 149 (2007). * Oregon Health & Science University. "Human skin cells converted into embryonic stem cells: First time human stem cells have been produced via nuclear transfer." ScienceDaily. ScienceDaily, 15 May 2013
Human skin cells converted into embryonic stem cells: First time human stem cells have been produced via nuclear transfer
* Seyyed Hassan Eslami Ardakani, ''Human Cloning in Catholic and Islamic Perspectives'', University of Religions and Denominations, 2007


External links


"Variations and voids: the regulation of human cloning around the world"
academic article by S. Pattinson & T. Caulfield
Cloning Fact Sheet


* ttp://science.howstuffworks.com/life/genetic/human-cloning1.htm How Human Cloning Will Work
Moving Toward the Clonal Man



United Nation declares law against cloning.
{{DEFAULTSORT:Human Cloning Biotechnology *