When a pair of scientists announced that they had isolated the first human embryonic stem cells, some researchers predicted that an experimental treatment for Parkinson's disease would be available in five to 10 years. That was five years ago; no human trials are in sight.
A short while later, a neurologist at the Johns Hopkins School of Medicine told patients experiencing the first twinges of Lou Gehrig's disease that he might offer them an experimental stem-cell therapy before the illness paralyzed and killed them.
But the long, slow grind of scientific discovery has taught researchers many things. One is not to make predictions.
Although scientists devoured two recent developments - the creation of 17 new stem-cell lines and the first progress toward therapeutic cloning - few dared to speculate on when the budding science would yield the first therapies.
"It's foolish to give timelines," said Dr. Jeffrey Rothstein, the Hopkins neurologist, who insists that he remains optimistic about harnessing stem cells against Lou Gehrig's disease. "When I talk to patients, I tell them we first learn how to build this machine."
Elsewhere on the Hopkins campus, biologist Michael Shamblott said the cloning report was "tremendously important," ranking alongside the birth of Dolly the cloned sheep in 1996. But he said major scientific hurdles await anybody wishing to offer a treatment, let alone a cure, based on cells culled from embryos.
"We consciously try to reel back the excitement," said Shamblott, who is working to transform stem cells into insulin-producing cells for Type-1 diabetics. "We consciously say what the obstacles are ahead of us."
Among the major obstacles is the difficulty of getting embryonic stem cells - master cells that generate every tissue in the human body - to become exactly the type of cell one wants.
For Shamblott, it means producing cells that might spare patients the burden of injecting themselves with insulin.
For Rothstein, it means motor neurons that signal muscles to move.
For others, it is neurons to mend spinal injuries, muscle cells to repair diseased hearts, or brain cells to replace those destroyed by Parkinson's.
Mimicking what goes on in a human embryo, scientists culturing stem cells in laboratory dishes have been able to steer them down one developmental path or another.
Scientists, however, haven't been able to guarantee purity - cells, for instance, that are destined to become muscle cells and nothing else.
"Say you have a million cells in a dish," said Dr. John Gearhart, a leading stem-cell researcher at the Hopkins medical school.
"Maybe 400,000 of them are what you want, so you've got to get rid of the others. Or maybe only a thousand are the ones you want."
Transplanting a mixed population of cells could cause the growth of unwanted tissues. The worst case could see stem cells morphing into teratomas, particularly gruesome tumors that can contain hair, teeth and other body parts.
Another issue is timing.
When to transplant
Stem cells pass through many intermediate stages before they become specialized cells such as motor neurons or pancreatic or heart cells. Deciding when to transplant remains an open question, and the answer might differ from disease to disease.
"So the question is, what stage is going to be optimal?" Gearhart said.
In tackling Lou Gehrig's disease, Rothstein figured that cells that haven't committed themselves to becoming motor neurons would stand the best chance, once implanted, of reaching out and connecting with the cells that surround them.
What he found, however, is that these immature cells didn't develop much once transplanted into lab animals.
"They stayed put," he said. Now he is trying his luck with fetal spinal-cord cells, which despite their name are more fully developed.
"We need to learn more about the cells before we can go into humans: their properties, how to use them, and which are the right cells for different injury conditions," Rothstein said.
In treating diabetes, the timing issue might not be as critical. But, Shamblott said, "We still have a lot of questions to answer."
One is whether the new pancreatic cells produce insulin in response to varying glucose levels in the blood. Another is whether they can produce enough insulin to take the place of the insulin shots and infusions that are the mainstays of treatment today.
Stem-cell scientists welcomed the news last week that a group of Harvard researchers had created 17 new embryonic stem-cell lines, more than doubling the number available in the United States for research. By using private funding, the Harvard team sidestepped federal funding restrictions on working with stem-cell lines created after August 2001.
Just three weeks earlier, the field received a big boost when South Korean scientists revealed that they had, for the first time, cloned a human embryo and cultured it long enough to extract stem cells.
Cloned embryos are created by plucking the nuclei out of adult cells and transferring them into eggs emptied of their DNA. Equipped with all the genetic information they need, the eggs start growing as if they are embryos.
The Korean scientists waited about a week until the embryos became blastocysts, hollow balls containing valuable caches of stem cells. Once the stem cells were removed and placed in a culture, the blastocysts died.
In theory, stem cells made from a person's DNA could be returned to his body without spurring a potentially fatal bout of rejection. This would spare patients the ordeal of taking immune-suppressing drugs that trigger painful side effects.
"That's the hypothesis, but we still need to prove it," said Dr. Jose Cibelli, a veterinary researcher at Michigan State University who has cloned cattle.
"If we can circumvent the rejection issue, life will be happy thereafter."
It can take up to a year to produce a useful supply of stem cells from a patient's DNA. That might be too long for those suffering from some terminal diseases. For them, it might be more practical to use stem cells derived from donated embryos and stored in a freezer - even if it means prescribing drugs to fight rejection.
Patients suffering from autoimmune disorders such as multiple sclerosis and diabetes could face rejection problems whether stem-cell therapies come from cloned or regular embryos, Shamblott said. These diseases come about when the immune system attacks a person's own tissue, mistakenly recognizing it as foreign.
Aside from the therapeutic potential, cloned embryos might give scientists an important window into how diseases work, said Dr. Irving Weissman, head of stem-cell research at Stanford University.
Scientists who used DNA from a person suffering from a known genetic disease could watch what goes wrong in a cell line at the very earliest stages of development. This might lead to better therapies, he said, whether or not they involve stem cells.
Before gaining approval for a human trial, researchers will have to prove any stem-cell therapy safe for animals ranging in size from rodents to monkeys.
Any problems along the way can mean long delays in the path toward cures - making any predictions a perilous matter.
Cibelli, who was listed as an author on the Koreans' paper because he reviewed and validated their work, said he gives the same answer to anyone asking how long it will take for a therapy to be ready.
"My answer is five years," he said. "It's the same thing as saying I have no idea."