In America it’s considered “politically incorrect” to speak indelicately of the disabled, hence the recent liberal outcry over Rush Limbaugh’s frank thoughts concerning political advertisements by actor Michael J. Fox. Like Mr. Fox, I too suffer spasms and twitches—from spinal cord injury rather than Parkinson’s disease. Like Mr. Fox my future depends on science. Like Mr. Limbaugh I am not politically correct.
As far as I’m concerned, Mr. Fox can do the Rumba to promote his social and political opinions. But the Fox advertisements go beyond worldviews. The embryonic stem cell hype that Fox presents as hope stands to affect the course of American politics, and with it the course of publicly funded science and the fates of countless human lives.
While praising Benjamin L. Cardin, Maryland’s Democratic candidate for the U.S. Senate, Fox proclaimed, “Stem cell research offers hope to millions of Americans with diseases like Diabetes, Alzheimer’s and Parkinson’s.”
Four years ago Australian scientists blasted the notion that stem cells could treat or cure Alzheimer’s disease, explaining that it’s a “whole brain disease.” Peter Rathjen, head of Molecular Bio-sciences at the University of Adelaide, told the Australian, “It’s bloody nonsense that stem cells might be able to cure Alzheimer’s. We don’t even know what causes it.” Other prominent Australian experts agreed, calling the hype “a bloody joke” and “outlandish”.
Two years ago, Michael Shelanski, co-director of an Alzheimer’s Institute at Columbia University’s Medical Center, told Rick Weis of the Washington Post, “I think the chance of doing repairs to Alzheimer’s brains by putting in stem cells is small.” Embryonic stem cell researcher Ron McKay of the National Institutes of Health likened the “story line” that stem cells offer hope for Alzheimer’s to telling “fairy tales.”
Michael J. Fox either doesn’t read the Post, or he forgot these reports and his advisers failed to remind him, or he likes to tell fairy tales and jokes concerning fatal diseases and crippling conditions.
Make no mistake, by “stem cell research” Fox refers to embryonic stem cells, since his preferred candidates in several states all support public funding of embryonic stem cell research without ethical or financial restrictions. Candidates opposed by Fox fully support adult stem cell and cord blood research, but keep their embryonic stem cell support within moral and ethical limits.
Before the upcoming elections, it’s crucial that American voters understand the nature of the ‘hope’ that Michael J. Fox is selling.
Square Pegs in Round Holes
Experts acknowledge that embryonic stem (ES) cells are unsafe for direct medical uses. In general their problems arise from a basic cause—ES cells are designed to function in embryos, not in adult (postnatal) tissues. Their genetic programming doesn’t work in adults; nor can they properly sense or respond to local signals in adult tissues. But since they’re programmed to grow, if they’re not rejected ES cells can grow out of control into clumps of random cells. These non-cancerous, but often fatal tumors are called teratomas.
The treatment of an American in China with fetal cells for Parkinson’s disease revealed this danger when the fetal cells either reverted to primitive ES cell stages, or ES cells were accidentally included in the transplant. A postmortem examination revealed that the cause of death was a growing mass in the patient’s brain consisting of hair, teeth, bone, skin, and other cell types—a teratoma.
To avoid this danger science must first mature ES cells to later fetal stages, when the cells should be more stable and more compatible with adult tissues. However, maturing ES cells in a petri dish creates additional “epigenetic” problems, meaning their genes are improperly turned on or off and adding to their instability. Clinical trials for Parkinson’s disease have been carried out in the U.S. using fetal cells from aborted or miscarried fetuses with mixed results.
“Patients began to worsen when cyclosporin therapy [immune suppression] was stopped,” said clinical investigator Dr. Thomas Freeman of the University of South Florida to the Society for Neuroscience. “Based on this profile of safety issues, the use of fetal tissue cannot be recommended.” He added, “These issues may be important when moving on to stem cell based therapies.”
Dr. Paul Green of Columbia University reported clinical results using fetal cells without immune suppression for Parkinson’s in 2003. Younger patients in his study displayed “measurable” improvements when off medication. However, fetal treatments failed to reduce involuntary movements in any age group, or reduce patient needs for medication.
“In the group of older patients in the study—the typical age range of individuals afflicted with PD—no improvement was derived from the implant, Green wrote in Medscape’s Neurological Focus. “Five of 33 implant-treated patients developed involuntary movements (dyskinesias or dystonia) that could not be eliminated by reducing antiparkinsonian medications.”
Round Pegs in Round Holes
The previous results pale in comparison to those produced using a patient’s own adult stem cells. Neurosurgeon Dr. Michael Levesque of L.A.’s Cedar Sinai Medical Center grew and matured less than fifty adult neural stem cells from Parkinson’s patient 57-year-old Dennis Turner into several million neurons, which he implanted in Turner’s brain under local anesthesia.
“At 1 year post transplantation, [the patient’s] Unified Parkinson’s Disease Rating Scale improved by 81% while on medication and 83% while off medication. Equivalent levodopa intake was reduced by 50%,” wrote Gary Vogin, MD of Levesque’s results in Medscape.
Last year Turner testified before a U.S. Senate Committee. Prior to his treatment he had been severely disabled by Parkinson’s disease.
“Soon after having the cells injected my Parkinson’s symptoms began to improve,” Turner told Senator Sam Brownback (R.-Kan.). “My trembling grew less and less, until to all appearances it was gone, only slightly reappearing if I became upset.”
Cell replacement for Parkinson’s can only be a treatment—not a cure—because replacing cells does not remove the cause of disease. This is also true of Diabetes and Alzheimer’s. Eventually Turner’s symptoms began returning.
“Last year, after four years of being virtually symptom free, my Parkinson’s symptoms began reappearing in my body’s left side,” Turner testified. “But I have no doubt that because of this treatment I’ve enjoyed five years of quality life that I feared had passed me by.”
Dr. Freeman reported that patients receiving fetal transplants for Parkinson’s disease had “no sustained improvements over two years.”
At the time of Turner’s testimony Levesque was accepting investments to fund an FDA-approved full-scale clinical trial of his treatment. However, a lawsuit over patent rights, filed by Stem Cells Inc., temporarily derailed this project. The lawsuit was dropped, but important investors had been scared off. Levesque currently has a third of the funds needed to conduct the trial.
Square Pegs—Back to the Drawing Board
Embryonic stem cells continue to behave like embryonic stem cells when implanted in adult tissues, despite cautious attempts to bring them to stable fetal stages. Last week Steven Goldman and colleagues at the University of Rochester Medical Center reported in Nature Medicine that after being treated with ES-derived cells, 100% of immune-suppressed rats with the animal model of Parkinson’s were killed when they developed “what looked like early tumors” in their brains. This follows a similar study in 2001, in which 20% of the rats died of teratomas.
Nor are problems with embryonic stem cell problems limited to direct medical uses. Their worth as disease “research tools” makes little sense as well.
A 2002 report by the Department of Environmental Health entitled “Parkinson’s and Pesticides” says of Parkinson’s Disease, “While genetic susceptibility is believed to play a large role in early onset Parkinson’s Disease, most cases in North America develop after age 50, suggesting that the majority of Parkinson’s Disease is caused by a factor other than genetics.”
Likewise, says the Institute of Science in Society, 456 scientists from 57 nations who believe that science should serve mankind, “the overwhelming causes of most human disease are environmental or lifestyle.” Therefore studying embryonic stem cells make no sense for studying “most human disease.”
Regarding diseases passed on through genetics, it’s irrational to expect information relating to defective embryos to be clinically effective in children or adults. Eyleen Goh, MD, of the John Hopkins University School of Medicine, says of research applicability in the Journal of Hemototherapy and Stem Cell Research:
“Equally important, we need to understand the neural development processes in the normal and diseased adult central nervous system environment, which is quite different from the embryonic central nervous system, where neural development has been traditionally investigated.”
Hope and Hype—the Difference
In concluding his Senate testimony, Dennis Turner said to Sam Brownback, “I wouldn’t hesitate for a second to have Dr. Levesque use my adult stem cells to treat me a second time, since in my case they were safe, effective, and involved no risk of rejection…I came here to offer him my sincere gratitude, and to offer others with Parkinson’s a concrete reason for hope.”
Michael J. Fox offers American voters a different kind of hope—the promise of waiting for years and perhaps decades for basic science to produce treatments that require life-long immune suppression, that carry risks of tumor formation, and offer the promise of fetal stage cells that have proved substantially inferior to adult stem cells for Parkinson’s Disease in humans, and for spinal cord applications in rats.
Near the end of his shortened life actor Christopher Reeve admitted that embryonic stem cells offer “nothing much” for treating or curing his condition, chronic spinal cord injury. Unfortunately Reeve had already swayed millions of Americans with his trusting endorsement of embryonic stem cells and human cloning, thus assisting those working to direct science down hugely problematic, but potentially lucrative paths.
Four years ago I realized that those morally opposed to killing embryos for research were protecting real causes for medical hope, whether they meant to or not. For me, their moral concerns regarding all human life may determine whether science moves in practical directions that lead to my walking again…to whether Michael J. Fox overcomes Parkinson’s disease … or spends his remaining days believing in fairy tales and passing them on to others.
Whoever Fox supports, Americans would be well advised to vote for their opponent.