Somatic cell nuclear transfer

In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory technique for creating an ovum with a donor nucleus (see process below). It can be used in embryonic stem cell research, or 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 cloning.

The process
In SCNT the nucleus, which contains the organism's DNA, of a somatic cell (a body cell other than a sperm or egg 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 reprogrammed 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 blastocyst (an early stage embryo 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 genetically matched to the donor organism. Presently, no human stem cell lines have been derived from SCNT research.

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 disease donated his or her somatic cells, then the stem cells resulting 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 rejection.

Only a handful of the labs in the world are currently using SCNT techniques in human stem cell research. In the United States, scientists at the Harvard University Stem Cell Institute, the University of California San Francisco, and possibly Advanced Cell Technology are currently researching a technique to use somatic cell nuclear transfer to produce embryonic stem cells. In the United Kingdom, the Human Fertilisation and Embryology Authority has granted permission to research groups at the Roslin Institute and the Newcastle Centre for Life. SCNT may also be occurring in China.

In 2005, a South Korean research team led by Professor Hwang Woo-suk, published claims to have derived stem cell lines via SCNT, but supported those claims with fabricated data. Recent evidence has proved the he in fact created a stem cell line from a parthenote.

SCNT in reproductive cloning
This technique is currently the basis for cloning animals (such as the famous Dolly the sheep), 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.

Limitations
The 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 microscope, SCNT is very resource intensive. The biochemistry involved in reprogramming the differentiated 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 DNA 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 also opposed to human embryonic stem cell research to be concerned about, or opposed to, SCNT research.

One concern is that blastula creation in 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 concern is the appropriate source of the eggs that are needed. SCNT requires human eggs, 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 syndrome,in very rare instances even death and may increase the risk of ovarian cancer.

Policies
SCNT is currently legal for research purposes in the United Kingdom, having been incorporated into the 1990 Human Fertilisation and Embryology Act in 2001. Permission must be obtained from the Human Fertilisation and Embryology Authority 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 Nations adopted a proposal submitted by Costa Rica, 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's 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.