Research into developing adult stem cells will produce life-saving medical breakthroughs—unless politics get in the way.
Many people argue, however, that ESCs may have greater potential to differentiate than ASCs-that, in scientific terminology, they are "more plastic." ESCs, they tell us, can ultimately be made into any type of mature cell in the body, whereas ASCs are much more limited in what they can become.
In fact, there is much evidence that ASCs may be far more plastic than once thought. Recently, Catherine Verfaillie and her colleagues at the University of Minnesotas Stem Cell Institute found stem cells in human marrow that appear to have the potential to form all three of the embryonic germ layers from which all mature cells eventually develop: ectoderm, mesoderm, and endoderm. "I think Verfaillies work is most exciting and translatable into the clinical arena," said Dr. David Hess, a neurologist at the Medical College of Georgia in Augusta. "[ASCs] seem to give rise to every cell in the body. She seems to have a subpopulation with basically all the benefits of ES cells and none of the drawbacks." Verfaillie calls the cells "multipotent adult progenitor cells," and has isolated them from mice, rats, and people. They have already been transformed into cells of blood, gut, liver, lung, brain, and other organs.
Therapeutic stem cell use from bone marrow transplants has been common since the early 1990s. The first successful use of umbilical cord stem cell therapy dates back to 1988, and now some seventy different diseases, primarily forms of leukemia, are treated with umbilical cord stem cells. Like bone marrow, cord blood is rich in stem cells, which can invigorate a recipients immune system. Studies indicate that cord blood stem cells are even less likely to provoke immune system rejection than bone marrow stem cells, because the babys immune system hasnt developed enough for recognition-it takes six to nine months for the immune system to develop fully after a baby is born. Furthermore, unlike marrow cells, cord cells are a cinch to collect. Originally, the only stem cells obtainable from cord blood were hematopoietic, meaning that they could grow into blood-forming tissue only. Boston-based ViaCell Inc., however, is pushing cord stem cells into becoming other types. They have already created more hematopoietic stem cells, plus mesenchymal and neural cells. Among the diseases its researchers are targeting are stroke, Lou Gehrigs Disease (ALS), and diabetes. "What ViaCell is doing is creating an ethical source of abundant stem cells with great plasticity," said ViaCell CEO Marc Beer.
Reporters Biased Agenda
Stem cells are being extracted now from tissues throughout the body.
The media gobbled it up. Agence-Presse France headlined, "Breakthrough in Adult Stem Cells Is Hype, Studies Warn." The Australian Associated Press (AAP) declared, "New Research Tips Debate on Stem Cells," and the Washington Posts subhead flatly declared, "Adult Cells Found Less Useful than Embryonic Ones." It was all terribly damning — and terribly false.
Stanfords Helen Blau countered with a big "So what?" in a Nature commentary (October 3, 2002), she noted that far from being "mere," "Cell fusion has long been known to achieve effective reprogramming of cells." In fact, her own laboratory had already been doing exactly that for twenty years. Far from showing that adult stem cell research is "hype," cell fusion may both complement and encourage the differentiation of adult stem cells that has already proved so valuable and promising.
The claim that cell differentiation was not occurring at all was simply bizarre in light of the myriad studies and therapeutic applications showing otherwise, including one that appeared in the journal Blood shortly thereafter (March 15, 2003). After showing that bone marrow stem cells can be converted into kidney cells, the study pointedly concluded, "The process does not involve cell fusion." "We found no evidence of nuclear material from two cells fusing into one cell," one of the co-authors emphasized to me. Tulane Universitys Darwin Prockop told me, "It may well be that fusion is part of the healing process. But clearly we can take mesenchymal cells and differentiate them into various tissues such as bone or fat because its been done over twenty years."
Umbilical cords from live births are an excellent source of highly plastic stem cells.
Just months later it was Natures prime competitor, Science, that was attempting to show that the earth really is flat after all, first with a letter in which researchers from the Baylor College of Medicine claimed that they had earnestly tried but failed to find bone marrow cells that had differentiated into brain cells, and later with a paper claiming to show that blood stem cells replenished marrow but appeared unable to create other tissues.
This second study evoked headlines such as United Press Internationals "Promise of Adult Stem Cells Put in Doubt" (September 5, 2002). The two Science pieces hardly justified a headline implicating all ASCs; nonetheless, they would have constituted a real setback if true. "Blood-forming stem cells from adults make blood," lead researcher Irving Weissman told UPI. Casting aside the usual cautionary scientific terminology of phrases such as "it appears" or "evidence indicates" or "our particular study has found," Weissman declared, "They [the cells] dont make brain; they dont make heart muscle or any of these things." However, any good scientist-and numerous critics of Weissman have told me that he is an excellent scientist-knows that a single study never proves anything. Weissman certainly knows that: a study published in Nature Medicine in November 2000 showed the opposite to be true. In that case, such cells rebuilt liver tissue when injected into mice. It is unlikely, moreover, that he did not know about that study — he was listed as a lesser co-author.
Bone marrow stem cell have been made into kidney cells in a process that clearly doesnt involve fusion.
"As to Weissmans paper, where you look and how you look determines what you see, and he doesnt define where hes looking," Blau said. "Our own experiments have shown there can be a thousand-fold [difference in the] frequency of stem cells depending on where you look." She also noted that his experiments cannot be replicated because he didnt say where he looked. "You could replicate ours, but he did not," she said. "The other false assumption he made was to look at a fraction of marrow, the hematopoietic part, and he looked in absence of any damage to the body, yet these cells are damage repair cells." In other words, one shouldnt think it remarkable that no ambulance shows up when theres no need for one.
Scientists Ulterior Motives
One possible explanation for Weissmans strange findings is evident. "Weissman has made it his mission to show adult stem cells dont have any potential," said Hess, who studies the use of bone marrow cells as a way of treating strokes. A year before his Science report, Weissman had admitted to the National Journal that he was an advocate of federal funding for embryonic research. Six months before publication, he called for such funding in congressional testimony. Weissman is highly influential. His views of stem cells have been quoted in literally hundreds of news stories over the last couple of years. In May, 2002, he was named California Scientist of the Year; eleven previous recipients have gone on to win the Nobel Prize.
Irving Weissman puts his mouth where his money is.
Dr. David Hess: "Weissman has made it his mission to show adult stem cells dont have any potential."
Some scientists have become quite dismayed at this disparity of coverage. In a commentary in the Journal of Cell Science in February 2003, British researchers noted that "despite such irrefutable evidence of what is possible, a veritable chorus of detractors of adult stem cell plasticity has emerged, some doubting its very existence, motivated perhaps by more than a little self-interest." Even scientists who strongly favor ESC funding readily admit that the issue has been highly politicized, with ASCs getting the short end of the stick from research publications, the popular media, and the scientific community. Blau and Propock are among them, as is Patricia Zuk, who works with Marc Hendrick at UCLA in differentiating stem cells from liposuctioned fat. "Certainly its politicized," says Zuk.
The problem is that the research pie is limited. After years of tremendous growth, the budget of the largest federal grant-maker, the National Institutes of Health (NIH), has leveled off. "NIH has a lot of discretion into what they can fund," says Hess, and although the NIH certainly can distinguish between real science and hype, to the extent that the public and the people on Capitol Hill holding the purse strings become convinced that ASC research is essentially worthless and ESCs have all the promise, money is more likely to flow to ESC research. "Everybody is fighting over the same pie, and theres a lot of pressure on NIH to give these scientists [those working with embryonic cells] what they want. And what they want is literally billions of dollars," said Hess.
ASCs Continuing Promise
Non-embyronic stem cells have been used in humans for decades; embryonics have just entered rodent testing.
ESC advocates believe research funds are a see-saw; the worse non-ESC cells look the better the ESCs look.
Nevertheless, the list of stem cell researchers who believe that adult stem cells may give us everything we need is long and growing. Dr. Adam J. Katz, a member of one of the research teams that spun fat into body tissues, has declared, "This discovery potentially could obviate the need for using fetal tissue." Added Katz, who works at the Division of Plastic and Reconstructive Surgery at the University of Pittsburgh School of Medicine, "We dont yet know the limits for stem cells found in fat. So far, we have seen promising results with all of the tissue types we have examined." An outside researcher commenting on Katzs work, Eric Olson of the department of molecular biology at the University of Texas Southwestern Medical Center in Dallas, noted that almost "every other week theres another interesting finding of adult cells turning into neurons or blood cells or heart muscle cells."
If Christopher Reeve walks again, it will have nothing to do with embryonic stem cells.
No honest researcher of stem cells of any type will deny that if stem cells are to help relieve the suffering of the many people with ailments such as those affecting celebrities Michael J. Fox and Christopher Reeve in the next few years, it will be those of the adult variety. To the extent that adult stem cell research loses funding or loses researchers who become demoralized by the full-court press being waged against them in both the scientific and popular media, it will be the ESC advocates who are preventing those cures.
The stem-cell controversy is one that technology can render obsolete, but only if politics stands down and lets ASC researchers do their work.
Read Michael Fumentos additional work on biotechnology.