By Rick Weiss
Washington Post Staff Writer
Monday, June 6, 2005
If only human embryonic stem cells could sprout anew from something other than a human embryo. Researchers could harvest them and perhaps harness their great biomedical potential without destroying what some consider to be a budding human life.
But like a low-calorie banana split or the proverbial free lunch, there is no such thing as an embryo-free embryonic stem cell.
Or is there?
In recent months, a number of researchers have begun to assemble intriguing evidence that it is possible to generate embryonic stem cells without having to create or destroy new human embryos.
The research is still young and largely unpublished, and in some cases it is limited to animal cells. Scientists doing the work also emphasize their desire to have continued access to human embryos for now. It is largely by analyzing how nature makes stem cells, deep inside days-old embryos, that these researchers are learning how to make the cells themselves.
Yet the gathering consensus among biologists is that embryonic stem cells are made, not born -- and that embryos are not an essential ingredient. That means that today's heated debates over embryo rights could fade in the aftermath of technical advances allowing scientists to convert ordinary cells into embryonic stem cells.
"That would really get around all the moral and ethical concerns," said James F. Battey, chief of the stem cell task force at the National Institutes of Health. The techniques under study qualify for federal grant support because embryos are not harmed, he noted. And eventually the work could boost the number of stem cell colonies, or lines, available for study by taxpayer-supported researchers.
The transformation of ordinary body cells into extraordinary stem cells is not a matter of alchemy but molecular biology. All human cells, be they stem or otherwise, have the same basic complement of genes. What is different about stem cells -- and what gives them their remarkable capacity to proliferate and morph into whatever kind of cell the body may need -- is the specific pattern of activity of their genes. It is all about which genes are working and which are dormant.
As cells mature during embryonic and fetal development, certain genes in those cells are switched either on or off. Depending on the new pattern of activity, each cell becomes skin, heart muscle, nerve or some other kind of specialized cell.
Now scientists are exploring methods for resetting the genetic switches inside various cells to the positions that will make them embryonic again. Both of the two major approaches now under study use existing embryonic stem cells (widely available from previously destroyed embryos and eligible for study using federal funds) to help ordinary cells become stem cells.
In one approach pioneered by Robert Lanza and colleagues at Advanced Cell Technology in Worcester, Mass., researchers pluck single cells from eight-cell embryos -- embryos so young they do not have stem cells yet.
Fertility doctors have known for years that early embryos seem unfazed by the removal of any one of their eight virtually identical cells, called blastomeres. In fact, it is common today to remove a single, representative blastomere from a laboratory-conceived embryo and test that cell for disease genes before deciding whether to transfer that embryo into a woman's womb.
Working with early mouse embryos, the team has found that single blastomeres, when cultivated in dishes with embryonic stem cells, can become what appear to be embryonic stem cells themselves. Chemicals secreted by the embryonic cells apparently flip the right genetic switches in the blastomeres to make them act "stemmy."
About a quarter to one-third of blastomeres treated this way can be coaxed to become embryonic stem cells or closely related embryo cells, said Lanza, who declined to release specific data pending publication in a peer-reviewed journal.
If this technique were applied to humans, then a single cell taken from an eight-cell fertility clinic embryo could give rise to a self-replicating line of embryonic stem cells without compromising the donor embryo's odds of someday growing into a baby.
"The president has said it is wrong to destroy a life to save a life," Lanza said. "This might be a way to get some cell lines that the president . . . can get behind."
Other researchers are experimenting with variations on a second approach. Chad Cowan and co-workers at Harvard University, for example, use chemicals to get an adult human skin cell to fuse with a human embryonic stem cell. The two cells become one with shared cellular contents, including two full batches of genes.
Experiments indicate that something in the stem cell "reprograms" the skin cell's genes, putting the hybrid cell into an embryonic state. The team is now developing ways to remove the original stem cell's DNA after reprogramming is complete. What will be left is an embryo-like cell that can be made to grow into all kinds of tissues -- all of which will be genetically matched to the person who donated the original skin cell.
Alan Trounson of Monash University in Australia has been performing similar experiments involving the fusion of mouse skin and stem cells. He recently reported he has developed a relatively simple system for removing that extra DNA after the skin cell's genes have been reprogrammed, offering hope that Cowan's work in human cells will indeed work.
And Yuri Verlinsky of the Reproductive Genetics Institute in Chicago reported at a meeting last month that he has succeeded in making new human embryonic stem cells by first removing the DNA from a stem cell and then fusing the rest of that cell with a human skin cell.
He has made 20 lines of stem cells this way, he said in an interview, acknowledging that he has yet to complete the battery of tests that will prove they can do everything an embryonic stem cell can do. "It's a work in progress," he said.
Researchers said several key challenges remain. Lanza has found it difficult, for example, to keep his newly made stem cells in an embryonic state. Most want to mature quickly into one kind of adult cell or another. Other scientists say it will take time to show that the stem cells they have made are genetically stable and healthy.
The ultimate challenge, scientists said, will be to get beyond their reliance on harvested embryonic stem cells and turn people's mature cells into embryonic stem cells of their own. To do so, researchers will have to identify the specific, switch-flipping chemical factors inside stem cells.
"The end hope is to determine the exact molecular components of reprogramming and get it down to something chemically useful so you can get adult cells to turn into any cell type you want," Cowan said. "That's the science fiction goal that we'd all like to see come true."
That cocktail of chemicals, synthesized in a lab and available off the shelf, could be the closest thing to a true elixir of life that science is ever likely to make.