The headline said it all: “American scientists develop technique for cloning monkeys”—or so we thought (see Choudhary, 1997). One week after Ian Wilmut’s announcement that he had successfully cloned a sheep named Dolly, scientists in Oregon reported that they had successfully cloned rhesus monkeys. Three years later, BBC News gave an update on this same group of researchers in an article titled “Scientists ‘clone’ monkey” (see Whitehouse, 2000). However, most researchers have dismissed these headlines and announcements, due to some fairly noteworthy “technicalities.” Truth be told, the Oregon Regional Primate Research Center has succeeded at cloning monkeys only from embryos, not from an adult animal. In the most recent case, they simply took an embryo that was at the eight-cell stage and split it into four genetically identical, two-cell embryos—in other words, little more than “artificial twinning” (Whitehouse, 2000). While these “technicalities” may seem insignificant, in light of recent announcements, the fact that we have never cloned monkeys from adult cells becomes extremely significant.
A major snag has developed in the race to see who can become the first person to successfully clone a human being. It appears that while researchers have no problems cloning sheep, goats, mice, cows, and rabbits, primates and humans may prove beyond our reach. Gerald Schatten, of the University of Pittsburgh School of Medicine, stated it is almost as if someone “drew a sharp line between old-world primates—including people—and other animals, saying ‘I’ll let you clone cattle mice sheep even rabbits and cats, but monkeys and humans require something more’ ” (as quoted in Vogel, 2003, 300:225, emp. added). In fact, scientists in the United States have reported that hundreds of attempts to clone monkeys have all ended in failure. Dr. Schatten and colleagues noted: “Although rhesus embryos begin development after embryonic cell nuclear transfer (ECNT), there has only been one report of rhesus births after ECNT, and that report has not been replicated” (Simerly et al., 2003, 300:297, parenthetical item in orig.). That one birth was a female monkey named Tetra.
Some might argue that researchers are simply giving up too soon—after all it took 277 failed attempts before Dolly was successfully implanted. However, Dr. Schatten and his colleagues used 724 eggs from rhesus monkeys, and their efforts resulted in only 33 embryos—with not a single viable pregnancy. And these are the results from only one lab. For several years, scientists all across the globe have been busily trying to clone both monkeys and humans. Schatten’s group has shifted its focus to what might be the cause of this “sharp line” that seems to be preventing humans from cloning primates. Researchers know that something “critical” is “left out” or missing during the initial stage where the DNA is stripped from the original cell. Dr. Schatten and his colleagues believe that “something” is motor proteins. Motor proteins play a critical role in properly organizing DNA, before a cell divides and grows. If the DNA is unable to duplicate itself perfectly before the cell divides, normal growth cannot occur.
As Vogel reported, a look at unfertilized rhesus eggs provided a key in pointing researchers toward an answer. Schatten and his colleagues found that “spindle proteins are concentrated near the chromosomes of unfertilized egg cells—the same chromosomes that are removed during the first step of nuclear transfer” (300:225, emp. added). In other mammals (i.e., non-primates), these proteins appear to be scattered throughout the egg; thus, when the egg’s chromosomes are removed, enough are left for cell division to proceed.
If this hurdle weren’t enough, biologist Rudolf Jaenisch of the Whitehead Institute in Cambridge, Massachusetts, and his colleagues found additional evidence of developmental problems for cloned animals. He reported in the April 15 issue of Development that genes important to early development frequently fail to be activated in mice embryos cloned from adult cells. Without these genes being turned on, the cloned embryos never get enough stem cells to grow on. These researchers compared gene activity from mice cloned from adult cells to those cloned from immature cells (pluripotent stem cells). The results from their experiment were easily observed, as the mice cloned from immature cells had higher survival rates and were far hardier than those from aged adult cells. As Robert Cooke noted:
Apparently, in the death of cloned embryos, important genes remain in their adult form—that is, they are shut down…. [E]ven if the genes are reprogrammed correctly, the rearrangement of chromosomes during cell division can still go haywire. In all mammal cases—natural or cloned—each new embryo must be a product of stem cells that have grown and differentiated to become all the various kinds of tissue the body needs. And during this process, if too few stem cells are made, or not enough of the right kinds of stem cells are made, the developmental program gets derailed (2003).
While scientists may eventually resolve the nuclear transfer problem by isolating those essential motor proteins, it is hard to imagine that there will be a “quick fix” for faulty gene regulation that Jaenisch and his colleagues uncovered. Such biological roadblocks may slow the race to produce a human clone. As Schatten noted: “This reinforces the fact that the charlatans who claim to have cloned humans have never understood enough cell or developmental biology” to succeed (300:227). Indeed it does.
Bortvin, Alex, Kevin Eggan, Helen Skaletsky, Hidenori Akutsu, Deborah L. Berry, Ryuzo Yanagimachi, David C. Page, and Rudolf Jaenisch (2003), “Incomplete Reactivation of Oct4-related Genes in mouse Embryos Cloned from Somatic Nuclei,” Development, 130:1673-1680, April 15.
Calvin, Simerly, Tanja Dominko, Christopher Navara, Christopher Payne, Saverio Capuano, Gabriella Gosman, Kowit-Yu Chong, Diana Takahashi, Crista Chace, Duane Compton, Laura Hewitson, and Gerald Schatten (2003), “Molecular Correlates of Primate Nuclear Transfer Failures,” Science, 300:297, April 11.
Choudhary, Naela, (1997), “American Scientists Develop Technique for Cloning Monkeys,” Discovery Channel, [On-Line], URL: http://www.exn.ca/Stories/1997/03/03/04.asp.
Cooke, Robert (2003), “WHY Cloning Fails,” Newsday.com, [On-Line], URL: http://www.newsday.com/news/printedition/health/ny-dsspdn3221172apr15,0,6599736.story?coll=ny-discovery-print.
Vogel, Gretchen (2003), “Misguided Chromosomes Foil Primate Cloning,” Science, 300:225-227.
Whitehouse, David (2000), “Scientists ‘Clone’ Monkeys,” BBC News, [On-Line], http://news.bbc.co.uk/2/hi/science/nature/602027.stm.
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