THE ANATOMICAL RECORD (NEW ANAT.) 257:1–2, 1999 1

EDITORIAL

Stem Cells and Cloning: What’s the Difference and Why the Fuss?

s a writer of embryology text- an embryo or an adult. In the case of nomic, a primary goal being the effi- books, I find myself regularly mammals, the fused cell is allowed to cient propagation of rare or valuable Awishing that my latest book divide a few times in vitro before being species. At this stage of our technol- hadn’t gone to press just a month implanted into the specially primed ogy, at least, the cloning of an indi- before the most recent major break- uterus of a surrogate mother. One of vidual or armies of humans from a through in embryotechnology. This the most difficult aspects of cloning single super donor in Hitleresque fash- year, the cause celebre was the twin has been matching the condition of ion is yet far away, but one learns announcements of the production of the donor nucleus with that of the egg, ‘‘never to say never’’ in the world of human embryonic stem cells derived so that cell division (embryonic cleav- technology. An unknown in present from the inner cell mass of the blasto- age) will occur. cloning techniques is the extent to cyst6 or from primordial germ cells What is often forgotten is that the which the mitochondrial DNA of the taken from 5-to-9-week-old human em- first cloning was done 40 years ago on host oocyte affects the phenotype of bryos.4 These reports, coupled with plants, when F.C. Steward of Cornell5 the cloned individual. Almost invari- the news account of an announcement was able to produce entire carrot ably the advent of a major new techno- that a private biotech company in plants from single somatic cells (the logical advance, such as cloning, has Massachusetts (Advanced Cell Tech- kind that we eat). Now in the agricul- preceded the establishment of an ethi- nology) claims to have produced em- tural world, cloning from somatic cells cal framework for it, no matter how bryonic stem cells by fusing a buccal long beforehand that advance might epithelial cell of a human with the have been anticipated. enucleated oocyte of a cow,7 have In the popular press, the Embryonic stem cell technology is spawned numerous articles and edito- distinction between stem based on older experimental embryo- rials that simultaneously extol the tech- logical work showing that individual nological leaps and decry our collec- cell technology and cells from the inner cell mass of the tive inability to provide an ethical basis cloning is often blurred. mammalian blastocyst are capable of for such work. forming any cell type in the body. As For at least the next few years, the Yet, despite superficial pointed out in the following article by public image of cloning will continue similarities in certain O’Shea,3 this technique involves the to be the indelible imprint of Dolly, the isolation of cells from the inner cell impassive sheep that was generated by aspects of technique, mass and their propagation in vitro fusing a mammary epithelial cell with the goals and processes under conditions that allow them to an enucleated egg. Dolly, by the way, remain pluripotent and to reproduce has by now produced a normal off- are quite different. themselves indefinitely. The goal of spring of her own in the old-fashioned embryonic stem cell technology is to way. identify environmental conditions that In the popular press, the distinction is routinely applied for the propaga- will lead the stem cell to differentiate between stem cell technology and clon- tion of many types of plants. The consistently into a uniform cell type. ing is often blurred. Yet, despite super- vertebrate equivalent of cloning began At this time, the use of embryonic ficial similarities in certain aspects of with the nuclear transplantation ex- stem cells has been a boon to those technique, the goals and processes are periments of Briggs and King in 1952,1 who are trying to unravel the molecu- quite different. A fundamental biologi- and the first production of a vertebrate lar pathways leading to the differentia- cal unifying factor, however, is the fact animal from an adult nucleus was tion of specific cell types. As pure that the nuclei of most cells in both accomplished by John Gurdon,2 who science, this is in itself a monumental embryos and adults contain a full inserted the nucleus from an intestinal goal and one that will require an im- complement of genetic information. epithelial cell of an adult Xenopus into mense amount of experimentation to As normally understood, cloning an enucleated egg. attain. Beyond understanding mecha- consists of fusing the nucleus of a Although initially cloning was used nisms of normal cellular differentia- donor cell (or the whole cell in the case to demonstrate some very important tion, stem cell technology can be used of Dolly) with an enucleated oocyte. scientific principles, the principal driv- to uncover information about the de- The donor cell can come from either ing force behind cloning today is eco- velopment of genetic mutants or about 2 THE ANATOMICAL RECORD (NEW ANAT.) EDITORIAL the developmental capabilities of cells cists and others in cloning experi- 4 Shamblott M J, Axelman J, Wang S, et al. that have been genetically engineered. ments. Especially when genetic ma- 1998. Derivation of pluripotent stem cells The holy grail at the end of these lines nipulation is involved, in either of from cultured human primordial germ cells. Proc Natl Acad Sci USA 95:13276–13731. of investigation is the production of these techniques concerns mount, not 5 Steward FC, Mapes MO, Kent AE, Hol- non-immunogenic cells that can be so much when somatic cells are the sten RD. 1964. Growth and development of used for the correction of genetic or target, but when the manipulation af- cultured plant cells. Science 143:20–27. pathological cellular deficiencies (e.g. fects germ cells that could transmit 6 Thompson JA, Itskovitz-Eldor J, Shapiro pancreatic beta cells in diabetics) or the manipulations to succeeding gen- SS, et al. 1998. Embryonic stem cell lines for the replacement of injured or killed erations. derived from human blastocysts. Science cells and tissues (e.g. necrotic myocar- 282:1145–1147. dial cells in infarcted regions of the 7 Wade N. 1998. Company says it has made heart). LITERATURE CITED embryonic cells that are part human, part Goals such as those outlined in the cow. Minneapolis Star Tribune, Nov. 13, 1 Briggs R, King TJ. 1952. Transplantation A27–A28. previous paragraph are usually consid- of living nuclei from blastula cells into ered laudable by commentators, but enucleated frogs’ eggs. Proc Natl Acad Sci Bruce M. Carlson USA 38:455–463. the ultimate source of the embryonic President, AAA 2 Gurdon JB. 1962. The developmental ca- stem cells is quite controversial, be- Department of Anatomy cause they are derived from human pacity of nuclei taken from intestinal epithe- lial cells of feeding tadpoles. J Embryol Exp and Cell Biology embryonic material. By way of con- Morphol 10:622–640. University of Michigan trast, it is not the origin of the cellular 3 O’Shea LS. 1999. Embryonic stem cell Ann Arbor, MI 48109 materials but the end product that has models of development. Anat Rec (New caused the most concern among ethi- Anat) 257:32–41. ௠ 1999 Wiley-Liss, Inc.