Why?
In a complex multicellular organism like a human, every cell contains the genetic 'blueprint' for performing the same functions as any other cell in the same organism. This means that a muscle cell could theoretically lose the ability to contract, start making neurotransmitters, and fully morph into a neuron. Obviously this does not happen under normal circumstances. This lack of plasticity makes sense from the point of view of evolution: if cell in tissues changed their identity willy-nilly, then organs could not count on the cells to perform their role when necessary.
However, a whole group of cell types, called stem cells, can change, in a process called differentiation, into other cells. A few varieties – embryonic, induced embryonic, amniotic fluid, trophoblast, and other ones researchers will no doubt soon discover – can (theoretically) differentiate into any cell in the organism. Imagine if doctors had these super-stem cells (called pluripotent or totipotent stem cells) for every patient; the stem cells could be used to make replacement tissue, such as skin or heart muscles, without fear of the immune system rejecting the transplant. These lab-grown tissues might also be used to test the responses of certain organs to drugs in order to screen patients for susceptibility to common side-effects of pharmaceutical agents. The problem is that most pluripotent stem cells are derived from an embryo in a procedure that destroys the embryo. With the exception of induced embryonic stem cells 1,2,3 (which have yet to be derived from a human), pluripotent stem cells currently cannot be created for an adult. But there is hope - a technique called somatic cell nuclear transfer (SCNT) may make possible therapeutic cloning and the creation of patient-specific pluripotent stem cell lines.
How?
The genetic information of a eukaryotic cell is stored in the nucleus. The behavior of the cell is controlled by both the state of activation of various genes and by all of the other molecules already present in the cell. In other words, the genetic information is filtered by the state of the cell. So what happens if the DNA from an unfertilized egg is replaced by DNA from an adult cell? Will the genetic information cause the cell to behave like an adult cell, or will the egg act as if it was just fertilized and go on to develop as normal?
Dr. Ian Wilmut from the Roslin Institute and a group of his collaborators from PPL Therapeutics performed such an experiment in 1997 4;. First, they removed the nuclei from two normal cells: an unfertilized sheep egg and an adult mammary gland cell. They then placed the nucleus of the adult cell next to the 'empty' egg cell and applied an electrical current. The two fused, creating cell with the 'shell' from the egg cell and the nucleus from the adult cell. When the procedure worked, the cell began to form an embryo in vitro as it would if it were a normal fertilized egg. After six days in culture the embryo, which was by then either a morula or a blastocyst, was implanted into the uterus of an ewe. After many, many attempts Dr. Wilmut and his colleagues succeeded in making the first documented clone of a mammal: the sheep Dolly had the same genetic makeup as the donor adult cell.
Due to obvious ethical problems, it seems unlikely that anyone will try to clone human for reproductive purposes. On the other hand, the embryo growing in vitro can be harvested for embryonic stem cells rather then being implanted into a uterus. Such therapeutic cloning would allow the creation of personalized embryonic stem cell lines. Much work remains since, discounting Dr. Woo Suk Hwang"s falsified claims 5,6, SCNT has yet to be used to make human pluripotent stem cells. Still, the vast amount of prior work with other species should serve as a strong foundation.
Brief History of SCNT in Cloning7
1938: Hans Spermann proposes cloning an organism using SCNT
1952: Frogs (Rana pipiens) cloned from tadpole and adult cells
1984: Fish (Carassius carassius) cloned from kidney cells
1996: Two lambs cloned from embryonic cells
1997: Dolly the sheep cloned from an adult cell
1998: Three generations of mice cloned from adult cells; eight calves cloned from slaughterhouse entails; and a clone made from the last surviving Enderby Island cow (Bos gaurus)
2000: Five piglets cloned from adult cells
2002: Cat (Felis domesticus) cloned – has different coat pattern then genetic donor
2003: Horse (Equus caballus) cloned from adult skin cell; a technically difficult technique was used to make a clone from a lab rat (Rattus norvegicus)
2005: Hwang's lab in South Korea clones a dog
- Okita, K, et al. Generation of germline-competent induced pluripotent stem cells. Nature 448: 313-317 (2007).
- Wernig, M, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448: 318-324 (2007).
- Maherali, N, et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1: 55-70 (2007).
- Wilmut, I, et al. Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810-813.
- Hwang, WS, et al. Patient-specific embryonic stem cells derived from human SCNT blastocysts. Science 308: 1777-1783 (2005).
- Kennedy, D. Retraction of Hwang et al., Science 308 (5729) 1777-1783. Retraction of Hwang et al., Science 303 (5664) 1669-1674. Science 311: 335 (2006).
- Wadman, M. Cloning special: Dolly: a decade on. doi: 10.1038/445800a