Researchers reveal early steps in clone development

Despite widely publicized reports about the sheep, Dolly and Polly, cloning is still not considered successful in the scientific community. Only two percent of clones succeed and they are sometimes unhealthy. To understand exactly where cloning goes wrong, researchers at Temple University School of Medicine (TUSM) examined and compared the earliest stages of development in normal embryos and cloned embryos.

“First, we mapped out some of the early steps an egg and sperm take to become an embryo,” said Keith Latham, PhD, associate professor of biochemistry at TUSM and lead author of the study. “Next, we examined how well clones were able to replicate these early steps. We discovered that at this stage of development, 100 percent of clones replicated the process entirely. This tells us that the problems must occur later in the development process.”

The study, “Rapid H1 linker histone transitions following fertilization or somatic cell nuclear transfer: evidence for a uniform developmental program in mice,” will appear in an upcoming issue of Developmental Biology. The study is part of a larger program, directed by Latham and funded by two National Institutes of Health (NIH) grants, that is examining how eggs communicate with chromosomes.

“When a sperm and egg unite, each brings a set of chromosomes to the table. Molecules in the egg turn the two sets of chromosomes, known as genomes, into an embryo. During cloning, we ask the egg to do the same thing but with different starting materials,” said Latham. “Instead of a sperm, the egg has to work with an adult cell from the organism that is being cloned. We used to think that during cloning, the egg integrated the adult cell as easily as it does the sperm.

“However, once the first few steps of development occur, the rest of the process is actually quite slow and incomplete. Cloned embryos bear characteristics of both an embryo and an adult cell. They’re not very happy and healthy.”

Latham suspects part of the problem is the culture used to house the cells in the laboratory. “We have cultures that work very well for embryos and cultures that work very well for adult cells. However, we still need to find the optimal culture media for cloned embryos. Once we find out what that is, cloning will probably be more successful,” said Latham.

“Understanding the early development process could help us increase success rates for cloning and its potential applications, such as producing valuable farm animals and preserving endangered species,” said Latham.

“As remarkable as it is to see clones born, cloning is really just a simple but striking demonstration of the truly remarkable processes that are at the root of each new life. We take this for granted, because it happens so readily, and yet when one gains an appreciation for the many complex things that must occur in order for each of us to be in the world, it really sinks in just how terrific the process is,” exclaimed Latham.

Temple researchers collaborated with researchers at the University of Utah Health Sciences Center and Peregrine pharmaceuticals on the project.