In
geneticsGenetics, , a discipline of biology, is the science of heredity and variation in living organisms. The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding...
and
developmental biologyDevelopmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis," which is the process that gives rise to tissues, organs and anatomy.Developmental biology is that...
,
somatic cell nuclear transfer (
SCNT) is a laboratory technique for creating a clonial embryo, using an
ovumAn ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
with a donor nucleus (see process below). It can be used in embryonic
stem cellStem cells are cells found in most, if not all, multi-cellular organisms. They are characterized by the ability to renew themselves through mitotic cell division and differentiating into a diverse range of specialized cell types. Research in the stem cell field grew out of findings by Canadian...
research, or, potentially, in regenerative medicine where it is sometimes referred to as "therapeutic cloning." It can also be used as the first step in the process of
reproductive cloningCloning in biology is the process of producing populations of genetically-identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or organisms...
.
The process
In SCNT the
nucleusIn cell biology, the nucleus , also sometimes referred to as the "control center", is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as...
, which contains the organism's
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
, of a
somatic cellSomatic cells are any cells forming the body of an organism, as opposed to germline cells. In mammals, germline cells are the spermatozoa and ova which fuse during fertilization to produce a cell called a zygote, from which the entire mammalian embryo develops...
(a body cell other than a
spermThe term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
or
eggAn ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
cell) is removed and the rest of the cell discarded. At the same time, the nucleus of an egg cell is removed. The nucleus of the somatic cell is then inserted into the enucleated egg cell. After being inserted into the egg, the somatic cell nucleus is
reprogrammedReprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development. After fertilization some cells of the newly formed embryo migrate to the germinal ridge and will eventually become the germ cells...
by the host cell. The egg, now containing the nucleus of a somatic cell, is stimulated with a shock and will begin to divide. After many mitotic divisions in culture, this single cell forms a
blastocystThe blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula, but before implantation. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast, which later forms the placenta...
(an early stage
embryoAn embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
with about 100 cells) with almost identical DNA to the original organism.
SCNT in stem cell research
Some researchers use SCNT in stem cell research. The aim of carrying out this procedure is to obtain stem cells that are
geneticallyGenetics, , a discipline of biology, is the science of heredity and variation in living organisms. The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding...
matched to the donor organism. Presently, no human stem cell lines have been derived from SCNT research.
Embryonic stem cells are new, unspecialized cells that are able to be produced into a specialized cell that can replace another cell that has been lost in the body.
A potential use of genetically-customized stem cells would be to create cell lines that have genes linked to the particular disease. For example, if a person with
Parkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills, speech, and other functions....
donated his or her somatic cells, then the stem cells resulting from SCNT would have genes that contribute to Parkinson's disease. In this scenario, the disease specific stem cell lines would be studied in order to better understand the disease.
In another scenario, genetically-customized stem cell lines would be generated for cell-based therapies to transplant to the patient. The resulting cells would be genetically identical to the somatic cell donor, thus avoiding any complications from
immune system rejectionTransplant rejection occurs when a transplanted organ or tissue is not accepted by the body of the transplant recipient. This is explained by the concept that the immune system of the recipient attacks the transplanted organ or tissue...
.
Only a handful of the labs in the world are currently using SCNT techniques in human stem cell research. In the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
, scientists at the
Harvard Stem Cell Institute,the
University of California San FranciscoThe University of California, San Francisco is one of the world's leading centers of health sciences research, patient care, and education. UCSF's medical, pharmacy, dental, nursing, and graduate schools are among the top health science professional schools in the world. The UCSF Medical Center is...
, Stemagen (La Jolla, CA) and possibly
Advanced Cell TechnologyAdvanced Cell Technology , a biotechnology company formed in 1994, is involved with therapeutic cloning and the cloning of animals. Among the animals it has cloned are transgenic cows....
are currently researching a technique to use somatic cell nuclear transfer to produce
embryonic stem cellEmbryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells....
s. In the
United KingdomThe United Kingdom of Great Britain and Northern Ireland is a sovereign state located off the northwestern coast of continental Europe. It is an island country, spanning an archipelago including Great Britain, the northeastern part of Ireland, and many small islands...
, the
Human Fertilisation and Embryology AuthorityThe Human Fertilisation and Embryology Authority is a statutory body in the United Kingdom that regulates and inspects all UK clinics providing in vitro fertilisation, artificial insemination or the storage of amphibian ova, sperm or embryos...
has granted permission to research groups at the
Roslin InstituteThe Roslin Institute is an animal sciences research institute at Roslin, a village in Midlothian, Scotland, that is sponsored by the Biotechnology and Biological Sciences Research Council...
and the
Newcastle Centre for LifeThe Centre for Life is a science centre located in the city centre of Newcastle upon Tyne, England. It is an educational charity which aims to promote greater interest and engagement in science as well as supporting scientific research...
. SCNT may also be occurring in China.
In 2005, a
South KoreaSouth Korea, officially the Republic of Korea and often simply referred to as Korea, is a country in East Asia, located on the southern half of the Korean Peninsula. It is neighbored by China to the west, Japan to the east, and North Korea to the north. Its capital is Seoul, the second largest...
n research team led by Professor
Hwang Woo-sukHwang Woo-suk is a South Korean veterinarian researcher. He was a professor of theriogenology and biotechnology at Seoul National University who became infamous for fabricating a series of experiments, which appeared in high profile journals, in the field of stem cell research...
, published claims to have derived stem cell lines via SCNT, but supported those claims with fabricated data. Recent evidence has proved that he in fact created a stem cell line from a
parthenoteParthenogenesis is an asexual form of reproduction found in females where growth and development of embryos occurs without fertilization by a male. In plants, parthenogenesis means development of an embryo from an unfertilized egg cell, and is a component process of apomixis...
.
The impetus for SCNT-based stem cell research has been decreased by the development and improvement of alternative methods of generating stem cells. Methods to reprogram normal body cells into
pluripotent stem cellsInduced pluripotent stem cells, commonly abbreviated as iPS cells are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes....
were developed in humans in 2007. The following year, this method achieved a key goal of SCNT-based stem cell research: the derivation of pluripotent stem cell lines that have all genes linked to various diseases. Some scientists working on SCNT-based stem cell research have recently moved to the new methods of induced pluripotent stem cells.
SCNT in reproductive cloning
This technique is currently the basis for
cloningCloning in biology is the process of producing populations of genetically-identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or organisms...
animals (such as the famous
Dolly the sheepDolly was a female domestic sheep remarkable in being the first mammal to be cloned from an adult somatic cell, using the process of nuclear transfer. She was cloned by Ian Wilmut, Keith Campbell and colleagues at the Roslin Institute near Edinburgh in Scotland. She was born on 5 July 1996 and she...
), and in theory could be used to clone humans. However, most researchers believe that in the foreseeable future it will not be possible to use this technique to produce a human clone that will develop to term.However, it is still a possibility and can become more probable in the future as it will probably need a few more adjustments to work for humans.
Limitations
Stresses placed on both the egg cell and the introduced nucleus are enormous, leading to a high loss in resulting cells. For example, Dolly the sheep was born after 277 eggs were used for SCNT, which created 29 viable embryos. Only three of these embryos survived until birth, and only one survived to adulthood. As the procedure currently cannot be automated, but has to be performed manually under a
microscopeA microscope is an instrument to see objects too tiny for the naked eye. The science of investigating small objects using such an instrument is called microscopy. Microscopic means invisible to the eye unless aided by a microscope.-History:An early microscope was made in 1590 in Middelburg, The...
, SCNT is very resource intensive. The
biochemistryBiochemistry is the study of the chemical processes in living organisms. It deals with the structure and function of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules....
involved in reprogramming the
differentiatedIn developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a single zygote to a complex system of...
somatic cell nucleus and activating the recipient egg is also far from understood.
In SCNT, not all of the donor cell's genetic information is transferred, as the donor cell's mitochondria that contain their own
mitochondrial DNAMitochondrial DNA is the DNA located in organelles called mitochondria, structures within cells that convert the energy from food into a form that cells can use...
are left behind. The resulting hybrid cells retain those mitochondrial structures which originally belonged to the egg. As a consequence, clones such as Dolly that are born from SCNT are not perfect copies of the donor of the nucleus.
Controversy
Proposals to use nucleus transfer techniques in human stem cell research raise a set of concerns beyond the moral status of any created embryo. These have led to some individuals and organizations who are
not opposed to human embryonic stem cell research to be concerned about, or opposed to, SCNT research.
One concern is that blastula creation in SCNT-based human stem cell research will lead to the reproductive cloning of humans. Both processes use the same first step: the creation of a nuclear transferred embryo, most likely via SCNT. Those who hold this concern often advocate for strong regulation of SCNT to preclude implantation of any derived products for the intention of human reproduction. , or its prohibition.
A second important concern is the appropriate source of the eggs that are needed. SCNT requires human
eggsAn ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
, which can only be obtained from women. The most common source of these eggs today are eggs that are produced and in excess of the clinical need during IVF treatment. This is a minimally invasive procedure, but it does carry some health risks, such as
ovarian hyperstimulation syndromeOvarian hyperstimulation syndrome is a complication from some forms of fertility medication. Most cases are mild, but a small proportion is severe.-Symptoms:...
, and in very rare instances even death.
One vision for successful stem cell therapies is to create custom stem cell lines for patients. Each custom stem cell line would consist of a collection of identical stem cells each carrying the patient's own DNA, thus reducing or eliminating any problems with rejection when the stem cells were transplanted for treatment. For example, to treat a man with Parkinson's disease, a cell nucleus from one of his cells would be transplanted by SCNT into an egg cell from an egg donor, creating a unique lineage of stem cells almost identical to the patient's own cells. (There would be differences. For example, the mitochondrial DNA would be the same as that of the egg donor. In comparison, his own cells would carry the mitochondrial DNA of his mother.)
Potentially millions of patients could benefit from stem cell therapy, and each patient would require a large number of donated eggs in order to successfully create a single custom therapeutic stem cell line. Such large numbers of donated eggs would exceed the number of eggs currently left over and available from couples trying to have children through
assisted reproductive technologyAssisted reproductive technology is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. It is reproductive technology used primarily in infertility treatments. Some forms of ART are also used in fertile couples for genetic reasons...
. Therefore, healthy young women would need to be induced to sell eggs to be used in the creation of custom stem cell lines that could then be purchased by the medical industry and sold to patients. It is so far unclear where all these eggs would come from. The sale of human eggs is normally referred to as a "donation," but women who donate their eggs are often paid thousands of dollars.
Stem cell experts consider it unlikely that such large numbers of human egg donations would occur in developed country because of the unknown long-term public health effects of treating large numbers of healthy young women with heavy doses of hormones in order to induce hyperovulation (ovulating several eggs at once). Although such treatments have been performed for several decades now, the long-term effects have not been studied or declared safe to use on a large scale on otherwise healthy women. Longer-term treatments with much lower doses of hormones are known to increase the rate of cancer decades later. Whether hormone treatments to induce hyperovulation could have similar effects is unknown. There are also ethical questions surrounding paying for eggs. In general, marketing body parts is considered unethical and is banned in most countries. Human eggs have been a notable exception to this rule for some time.
To address the problem of creating a human egg market, some stem cell researchers are investigating the possibility of creating artificial eggs. If successful, human egg donations would not be needed to create custom stem cell lines. However, this technology may be a long way off.
Policies
SCNT is currently legal for research purposes in the
United KingdomThe United Kingdom of Great Britain and Northern Ireland is a sovereign state located off the northwestern coast of continental Europe. It is an island country, spanning an archipelago including Great Britain, the northeastern part of Ireland, and many small islands...
, having been incorporated into the 1990 Human Fertilisation and Embryology Act in 2001. Permission must be obtained from the
Human Fertilisation and Embryology AuthorityThe Human Fertilisation and Embryology Authority is a statutory body in the United Kingdom that regulates and inspects all UK clinics providing in vitro fertilisation, artificial insemination or the storage of amphibian ova, sperm or embryos...
in order to perform or attempt SCNT.
In the United States, the practice remains legal, as it has not been addressed by federal law.
In 2005, the
United NationsThe United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and the achieving of world peace...
adopted a proposal submitted by
Costa RicaCosta Rica, officially the Republic of Costa Rica is a country in Central America, bordered by Nicaragua to the north, Panama to the east and south, the Pacific Ocean to the west and south and the Caribbean Sea to the east.Costa Rica, which translates literally as "Rich Coast", constitutionally...
, calling on member states to "prohibit all forms of human cloning inasmuch as they are incompatible with human dignity and the protection of human life." This phrase may include SCNT, depending on interpretation.
The
Council of Europe'sThe Council of Europe is the oldest international organisation working towards European integration, having been founded in 1949. It has a particular emphasis on legal standards, human rights, democratic development, the rule of law and cultural co-operation...
Convention on Human Rights and Biomedicine and its
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, on the Prohibition of Cloning Human Being appear to ban SCNT. Of the Council's 45 member states, the
Convention has been signed by 31 and ratified by 18. The
Additional Protocol has been signed by 29 member nations and ratified by 14.
See also
- Stem cell research
- Stem cell controversy
The stem cell controversy is the ethical debate centered only on research involving the creation, usage and destruction of human embryos. Most commonly, this controversy focuses on embryonic stem cells.- Background :...
- Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops. It starts with the fertilization of the ovum which, after fertilization, is referred to as a zygote. The zygote undergoes rapid mitotic divisions with no significant growth and cellular differentiation, leading to...
- In vitro fertilisation
In vitro fertilisation is a process by which egg cells are fertilised by sperm outside the womb, in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed...
- Cloning
Cloning in biology is the process of producing populations of genetically-identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or organisms...
- New Jersey legislation S1909/A2840
S1909/A2840 is a bill that was passed by the New Jersey legislature in December 2003, and signed into law by Governor James McGreevey on January 4 2004, that permits human cloning for the purpose of developing and harvesting human stem cells...
- Rejuvenation
Rejuvenation is the hypothetical reversal of the aging process.Rejuvenation is distinct from life extension. Life extension strategies often study the causes of aging and try to oppose those causes in order to slow aging...
External links