To many scientist, these amazingly powerful cells are the most promising medical
breakthrough in a long time. But to others, this is murder, and their protests have turned a cutting-edge field of biology into a fierce political battleground.
But while researchers of embryonic stem cells contend with public furor over their work, other researchers are looking for a "politically correct" alternative, stem cells present in all adults that may offer a range of cures without requiring human embryo destruction.
If these adult stem cells can match their embryonic counterparts in healing power, then many Americans conflicted over this new biology may be able to have their cake and eat it, too: cures without harm to embryos. So, who is winning the race?
The short answer is: It's too soon to tell, though most biologists say embryonic stem cells appear to have far more healing potential. These cells are present in week-old embryos and eventually give rise to every tissue in the human body.
The trick - and it is a tough one - is to control and implant these cells into patients where they can conceivably repair tissue damage. This has not been done on humans to date, though several mouse studies indicate it's possible, and some researchers predict tests on Parkinson's disease patients within five years.
In contrast, it's not clear that adult stem cells, present in every human, have the same plasticity, or ability to morph into many tissues. It's thought they can only form a handful of tissues needed for localized healing. Stem cells in blood, for instance, can only become several types of blood cells but not nerve or kidney cells.
For researchers, the burden of proof in this stem cell race, therefore, rests with adult stem cell researchers: They must prove their cells are as adaptable as those in embryos.
University of Minnesota professor Catherine Verfaillie accelerated the race last June when she released a paper asserting that stem cells in adult bone marrow can turn into brain, retina, lung, heart, muscle, intestine, kidney, spleen, marrow and skin tissue.
The media trumpeted the newfound promise in adult stem cells. Antiabortion lawmakers seized on her results to bolster their efforts to ban embryonic stem cell work, arguing it was no longer necessary. Antiabortion groups still feature the results prominently on their Web sites and press releases. Though Verfaillie released a statement declaring that both adult and embryonic stem cell research should continue, her work became a flashpoint.
"Even though we're excited about the fact that there seem to be cells in adult tissue that seem to have greater potential than we thought, it's too soon to say they have the same potential and capabilities as embryo cells," Verfaillie told a congressional panel last year.
So far, no one has been able to reproduce Verfaillie's remarkable experiments in the lab. In fact, one recent Stanford University study appeared to cast doubt on her results.
"A lot of people jumped on Catherine's data," said Dr. Robert Lanza, chief scientist for Worcester-based Advanced Cell Technology Inc., a cloning and embryonic stem cell firm. "There's no question I believe her data. But I think, though, that there are questions."
The ongoing discussion in the scientific community over Verfaillie's work is center stage in the embryonic-versus-adult stem cell debate, offering a first glimpse into a scientific conflict likely to go on for years.
Embryonic stem cells appear quickly after an egg is fertilized, dividing and changing, slowly giving rise to organs and bones and muscles - everything that makes up human beings.
Adult stem cells are a bit more complex than their embryonic brethren. First, there are several kinds, unlike the single, primordia embryonic stem cell. And the adult cells don't appear to be able to form all tissues, instead becoming the tissues present only in their immediate bodily environments.
Researchers first detected adult stem cells four decades ago. They've since found that adult bone marrow contains two types of stem cells that become multiple blood cell types, bone, cartilage, fat and connective tissue. In addition, the brain contains stem cells that morph into neurons and nerves, and the digestive tract and skin contain stem cells that convert into tissue useful in those regions of the body.
Verfaillie's team injected a single adult stem cell, taken from bone marrow, into early-stage mouse embryos. When the mice were born, they found that the stem cells had integrated themselves into almost every major organ, suggesting enormous plasticity. In a second experiment, they injected adult bone marrow stem cells into the tail veins of mice, and found again that the cells became part of the mouse blood, marrow, spleen, lung, liver and intestine.
"It's a fascinating study that we're still digesting in the scientific community," said Dr. George Daley, a stem cell researcher at the MIT-affiliated Whitehead Institute and Harvard Medical School. "I think it's still too early to ask for a significant amount of validation from the rest of the scientific community. Her paper has only been out a few months. The jury is still out."
Last September, however, a Stanford University team, led by Dr. Irving Weissman, offered what seemed like a rebuttal to Verfaillie's work.
Weissman's team performed two striking experiments. First, they took a single adult bone marrow stem cell, tagged it with a fluorescent marker, then injected it into a mouse whose own blood stem cells had been destroyed by radiation.
Based on Verfaillie's results, the stem cell would have become all sorts of tissue types. Weissman's group found it became an ample supply of blood cells, but just one brain cell, seven liver cells and nothing else - not much plasticity.
Next, they surgically joined two mice to create a single circulatory system between them. They had tagged the adult bone marrow stem cells of one mouse and found those cells, after migrating to the other mouse, formed only blood cells. Again, low plasticity.
How to make sense of these seemingly contradictory results?
A technical point may offer answers, scientists say. Verfaillie's adult stem cells were grown in petri dishes for many months, with cells kept in low-density piles. Researchers hypothesize that these unusual growth conditions allowed the cells to somehow change to more resemble embryonic stem cells. By comparison, Weissman's study grew the cells more quickly.
"The cells [in Verfaillie's study] seem to forget who they are," allowing them to be coaxed into many different kinds of cells, Daley said. He noted that dozens of labs are currently investigating the theory that adult stem cells can be engineered in the lab much like Verfaillie did.
But the fact that adult stem cells may require extra manipulation to turn them into different body tissues may point to one of the key advantages of embryonic cells: It's in their very nature to become tissue, and scientists suspect it will be far easier to convert them into adequate tissue amounts needed to heal millions of patients. Harvard Medical School stem cell specialist Dr. Stuart Orkin noted that it took Verfaillie more than a year to prepare her cells.
"How practical is her system, really?" he said.
But most scientists would just as soon see both avenues of research blossom side by side. Indeed, both show promise.
A study released three weeks ago by German and Chinese scientists revealed that adult bone marrow stem cells transplanted into the hearts of patients with cardiac disease turned into blood vessel cells that brought in a fresh blood supply that repaired some of the patients' heart damage. And on the same day Verfaillie's headline-grabbing study came out, Ron McKay of the National Institute of Neurological Disorders and Stroke reported that his team had converted mouse embryonic stem cells into a type of neurons that could help treat Parkinson's disease. With hundreds of stem cell experiments now unfolding worldwide, the comparisons between the promises of adult and embryonic stem cells may be considerably clearer a year from now.
Copyright © 2003 LexisNexis, a division of Reed Elsevier Inc. All rights reserved.
