The Stem Cell Cover-Up
Posted May 24, 2004 Insight Magazine
By Michael Fumento
Activists such as Christopher Reeve have it backward when they say that
restrictions on funding for embryonic stem-cell research will prevent him
from walking again.
Stem-cell research constitutes one of the most exciting areas in medical
science. It promises to prevent, ameliorate and cure diseases for which
there are now few if any treatments. Far easier is listing what stem cells
don't have the potential to do, but here are a few of the wonders in
progress:
More than 30 anticancer uses for stem cells have been tested on humans,
with many already in routine therapeutical use.
By some accounts, the area in which stem-cell applications are moving
fastest is autoimmune disease, in which the body's own protective system
turns on itself. Diseases for which stem cells currently are being tested
on humans include diabetes, lupus, multiple sclerosis, Evans syndrome,
rheumatic disease and amyotrophic lateral sclerosis (Lou Gehrig's
disease), among many others.
Just last February, two different human-autopsy studies demonstrated that
stem cells transfused into the marrow work their way into the brain, where
they can repair neurons and other vital cells. Other studies have shown
that when injected into animals with severed spinal cords, stem cells rush
to the injury site effecting repairs. "I think the stem cells may act as a
repair squad," says the leader of one of the two studies, Helen Blau of
the Stanford University Brain Research Institute. "They travel through the
bloodstream, respond to stress, and contribute to brain cells. They
clearly repair damage in muscle and other tissues."
At a conference in late 2002, French researchers reported that during the
last 14 years they had performed 69 stem-cell transplants with an 85
percent disease-free survival rate. Since improving their procedure in
1992, all 30 of the last transplants have been successful.
Stem cells have been injected into damaged hearts and become functional
muscle. This destroyed the dogma that heart muscle cannot be repaired,
just as stem-cell research also wrecked the firmly held belief that brain
tissue cannot regenerate.
Unless you've spent the last several years stranded on a deserted island,
you've probably heard of at least some of these medical miracles. But
here's what you may have missed. While the overwhelming majority of
favorable media coverage of stem cells concerns those pulled from human
embryos, called embryonic stem cells (ESCs), not a single treatment listed
above has used that kind of cell. In fact, while activists such as
spinally injured actor Christopher Reeve rage that but for Bush
administration and congressional restrictions on ESC funding he might be
walking in a few years, there are no approved treatments - and have been
no human trials - involving embryonic stem cells. Each of the above
therapies and experiments has involved cells that require no use of
embryos.
These are called "adult stem cells" (ASCs), though they also refer to
cells found in nonadult tissue such as umbilical cords, placentas and
amniotic fluid. Like ESCs, they are precursors that eventually will become
a mature, specialized cell. ASCs actually have been used therapeutically
to treat leukemia and other diseases since the 1980s. A bone-marrow
transplant is a transplant of stem cells from marrow.
Yet when an ESC so much as hiccups, it makes international news, while
tremendous breakthroughs with ASCs are as a rule ignored. Welcome to
what's been called "stem-cell wars," a deliberate effort to downplay the
proven value of ASCs to attract more attention to the potential of ESCs.
It is a war that is being fought partly over ethics, but mostly over
money.
Okay, so if ASCs have such a huge advantage over ESCs then why did anybody
begin researching ESCs anyway, to a point where labs and researchers all
over the world now are working with them?
Blame it on the dogma - scientific dogma that is. It's long been
acknowledged that ESCs carry a boatload of physiological and ethical
problems. For example, ESCs implanted into animals have a nasty tendency
to cause malignant tumors. That's a major hurdle to overcome, as is the
fact that the body rejects them just as it rejects donated organs. Yet it
was always believed that ESCs had one huge advantage over their ASC
counterparts -- that while an ASC could become or "differentiate" into
only a few types of mature tissue with those tissues dictated by the
source of that ASC, the ESCs could become any type of tissue in the entire
body. In medical terminology this is known as "plasticity."
But this has never been more than theory, and lately that theory has
begun crumbling under the weight of empirical findings. Or, in other
words, it's had a run-in with reality.
"We do not yet know enough about adult stem cells or ESCs to make
dogmatic statements of either," declared Dr. Darwin Prockop, director of
the Gene Therapy Center at Tulane University, in a letter that appeared in
Science.
"There's no law of physics or such that I know of that says that [ASCs]
are inherently more limited than embryonic stem cells," Prockop told
Citizen.
We do know that ESCs give rise to all three germ layers (as in
"germination") that become all the forms of human tissue. But this doesn't
necessarily mean that they can be converted into each and every one of
those tissues. Moreover, Catherine Verfaillie and her colleagues at the
University of Minnesota's Stem Cell Institute recently have found stem
cells in human marrow that appear to transform into all three germ layers.
"I think Verfaillie's work is most exciting and translatable into the
clinical arena," says Dr. David Hess, a neurologist at the Medical College
of Georgia in Augusta. "They seem to give rise to every cell in the body.
She seems to have a subpopulation with basically all the benefits of ESCs
and none of the drawbacks."Verfaillie calls the cells "multipotent adult
progenitor cells," and has isolated them from mice, rats and people. They
already have been transformed into cells of blood, the gut, liver, lung,
brain and other organs. Just a few months ago, researchers at the Robert
Wood Johnson Medical School in New Jersey published a paper explaining
that in a mere five hours they had been able to convert bone-marrow cells
into neurons both in petri dishes and in rats. Under the old dogma, that
was simply impossible. More importantly, "We found that they express genes
typical of all three embryonic germ layers," the researchers told Citizen.
"In aggregate, our study and various others do support the idea that one [ASC]
can give rise to all types of tissue."
And the good news keeps pouring in. One problem with Verfaillie's cells
is that, in part because they come from marrow, they are difficult to
extract. That problem won't matter down the road when culturing practices
are perfected, say researchers, but currently it hinders efforts to keep
labs supplied.
Enter Elizer Huberman and his colleagues at the Argonne National
Laboratory outside Chicago. They wanted to find highly plastic ASCs in
blood, as they would be far easier to extract and to store. Just how
plastic they might be remained to be seen and wasn't even a prime concern.
But when the Argonne scientists reported their results in the March 2003
issue of the Proceedings of the National Academy of Sciences, it showed
that their stem cells had in fact differentiated into mature cells of all
three lineages that ESCs can produce.
Even if it somehow turned out that none of the ASCs really can produce all
the cells of the body, perhaps we don't need the ability of cells that are
"one size fits all." That's because in recent years researchers have found
that they can tease ASCs into many more types of mature tissue than was
previously thought possible. Moreover, researchers now seem to be finding
ASCs essentially wherever they look - including blood, bone marrow, skin,
brains, spinal cords, dental pulp, muscles, blood vessels, corneas,
retinas, livers, pancreases, fat, hair follicles, placentas, umbilical
cords and amniotic fluid. You don't need "one size fits all" if you can
provide all sizes.
At the same time, ESCs have become even more suspect ethically in the eyes
of many people. The original ethical concern was that many see the
destruction of human offspring, no matter how young, as an abortion. Some
prominent abortion opponents believe human life only begins upon
implantation in the uterine wall; therefore destruction of embryos would
not count as such. Nonetheless, even to some of these people the thought
of ripping apart the byproduct of human conception for the sake of science
invokes images of Nazi eugenicist Josef Mengele or of Mary Shelley's Dr.
Frankenstein.
This more recent worry has nothing to do with destroying life but rather
with the creation of it - cloned human life. While growing embryos into
blastocysts (see note at end of article) often is referred to as
"therapeutic cloning" or "research cloning" to distinguish it from the
process of creating a human being, the two processes follow parallel
tracks. If that blastocyst is implanted into the womb and it survives,
voila! - nine months later you have a clone just like something out of
Star Wars Episode II. No doubt most ESC researchers haven't the least
desire to take the next step, but that's not the issue. What counts is
that they are developing a technology that others can build upon to refine
the process of creating human clones.
Thus, ESCs have in their favor nothing more than a decaying theory that
they may have greater plasticity. Going against them are the ethical
concerns and that they are years behind ASCs in commercial applications.
But there's a huge ESC industry out there, with countless labs packed with
innumerable scientists desperately seeking research funds. Private
investors avoid them because they don't want to wait perhaps 10 years for
commercial products that very well may not materialize and because they're
spooked by the ethical concerns. That leaves essentially only Uncle Sam's
piggy bank, primarily grants from the National Institutes of Health, to
keep these labs open. This, in brief, explains the "stem-cells wars," the
perceived overwhelming need grossly to exaggerate petri-dish advances with
ESCs, while life-saving new applications of ASCs are downplayed or
ignored.
Thus the announcement in 2001 that ESCs could be made into blood cells
received almost 500 "hits" on the Nexis media database even though
published medical-journal reports of ASCs differentiating into blood cells
go back at least to 1971. It's possible to read lengthy articles on the
promise of stem cells that mention nothing but ESCs. The influential
pro-life figure and former U.S. senator Connie Mack (R-Fla.) even
questioned whether ASCs exist, which is on par with questioning the
existence of Starbucks.
It's probably not a coincidence that Mack has been a paid lobbyist for
ESCs, but most reporters have no financial stake in the issue and it is a
complex one. They take their cues from the professional medical journals.
And, unfortunately, these are among the leaders in the war against ASCs.
The world's most prestigious science journal, Nature, published two
in-vitro studies in March 2002 widely interpreted to mean either that ASCs
are grossly inferior to what had earlier been believed or even that
they're outright worthless.
The Nature writers indicated their studies showed that ASCs probably were
not differentiating and multiplying at all; rather that it appeared the
cell nuclei were merely fusing and the resulting fusion gave the
impression of a new, differentiated cell forming. 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." The Washington Post's subhead flatly
declared: "Adult Cells Found Less Useful than Embryonic Ones." It was
damning ... and false.
Stanford's Helen Blau countered with a big "So what?" In a Nature
commentary, she noted that "Cell fusion has long been known to achieve
effective reprogramming of cells" - so long in fact that her own
laboratory was doing it 20 years earlier. Thus, far from showing that ASC
research is "hype" or whatever term the particular newspaper or newswire
chose to apply, it turns out that cell fusion both complements and
encourages the differentiation of adult stem cells - something that's
already proved valuable and is clearly very promising.
The idea that differentiation wasn't happening at all was simply bizarre
in light of myriad studies and therapeutic applications showing otherwise,
including one that appeared in the journal Blood shortly thereafter.
Showing that bone-marrow stem cells can be converted into kidney cells, it
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 coauthors emphasized to me. In an interview last spring,
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 because it's into bone or fat and it's been done over
20 years." Indeed, he specifically explored the fusion issue in a study
released in the Sept. 30, 2003, issue of the Proceedings of the National
Academy of Science concluding "Most of the [mesenchymal cells]
differentiated without evidence of cell fusion, but up to one-quarter
underwent cell fusion with the epithelial cells. A few also underwent
nuclear fusion."
Yet another Blood study released last September concluded, "Analysis of
DNA content indicates that donor-derived endothelial [stem] cells are not
the products of cell fusion." A Lancet study in early 2003 looked at cheek
cells from five living women who had received bone-marrow transplants from
their brothers several years earlier. They found cells containing the male
Y chromosome, a sign that donor marrow stem cells had differentiated into
cheek cells. Moreover, the group found almost no evidence of fusion among
the cells in the cheek. Of the 9,700 cells that were examined in the
study, only two showed signs of possible fusion.
And yet in late October 2003, Nature rushed into publication yet another
letter claiming that there was no evidence that stem cells from marrow do
anything but fuse. Of all these studies, guess which was the only one to
get media attention - and lots of it.
Shortly after Nature's first effort to establish that the wheel doesn't
exist, its chief competitor, Science, attempted to show that the Earth is
flat after all. First it ran a letter in which authors from the Baylor
College of Medicine claimed that they earnestly had tried but failed to
find bone-marrow cells that had differentiated into neurons in the brain.
Shortly thereafter it ran a paper from Stanford University scientists, led
by Irving Weissman, claiming to show that a type of stem cell from marrow
could replenish that type of marrow, but that it appeared worthless for
creating other tissues. The typical media reaction was UPI's "Promise of
Adult Stem Cells Put in Doubt." Weissman eschewed the usual cautionary
scientific terminology such as "it appears" or "evidence indicates," or
"our particular study has found." Instead he smugly told UPI: "They [the
cells] don't make brain; they don't make heart muscle or any of these
things."
According to Blau, it was surprising to see this published so rapidly and
in such a prestigious and influential publication as Science. The Baylor
study, she notes, failed to detect not only neurons but also something far
more readily detectable called microglial cells. And forget that "At least
20 reports over the past 15 years have shown that bone-marrow
transplantation results in readily detectable replacement of a large
proportion of microglial cells in the brain." Some of these reports have
even appeared in Science. Says Blau, "If they couldn't see those, how
could they possibly see neurons?" It would be like announcing that you had
failed to detect a tiny virus under your microscope when you also hadn't
been able to see a gnatthat accidentally got trapped between the slides.
Either your microscope is faulty or you don't know how to use it.
"As to Weissman's paper, where you look and how you look determines what
you see, and he doesn't define where he's looking," she says. "Our own
experiments have shown there can be a thousand-fold frequency of stem-cell
incorporation depending on where you look." Because he didn't say where he
looked, "It would be quite difficult to replicate his experiments," she
notes. "You could replicate ours, but he did not. 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 are
damage-repair cells." In other words, one shouldn't think it remarkable
that no ambulance shows up when there's no need for an ambulance.
Weissman is also a notorious opponent of adult stem-cell research insofar
as he has made millions of dollars with numerous companies that work with
ESCs, according to an exposé in the Washington Monthly. "Was the
publication of these two papers a political act designed to harm the image
of ASCs in the image of the public?" Insight asked Blau.
"That's been a question in many people's minds," she says. "Why these
negative findings should have been published in such a prominent way does
suggest a political agenda."
In a commentary in the Journal of Cell Science in February 2003, British
researchers asked in the very title: "Plastic Adult Stem Cells: Will They
Graduate From the School of Hard Knocks?" In a good-humored, indeed
sometimes humorous, piece the angst nonetheless came through. "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."
While certain issues still need resolving, the researchers said,
"slamming" the "whole field because not everything is crystal clear is not
good science."
Even scientists who strongly favor ESC funding readily admit that the
issue is highly politicized, with ASCs getting the short end of the stick
from research publications, the popular media and the scientific
community. Blau, Prockop, Black and Verfaillie are among them. "Most
scientists never want a door closed, they want all doors open," says Hess.
"And anybody who disagrees with that stance is seen as trying to hold up
medical progress."
Another ASC researcher who strongly supports funding for ESCs is Patricia
Zuk, whose lab has shown that America's most plentiful natural resource -
body fat - can provide a limitless source for stem cells capable of
differentiating into bone, muscle, cartilage and fat that can be used to
fill in scars and wrinkles. "Certainly it's politicized," she says. But,
she adds, "I think a lot of embryonic stem-cell people are right in trying
to protect their jobs."
Understandable, yes. But is it right? Forget for the moment the
questionable morality of a mass campaign to fool the American public. Zuk
admits that the stem-cell wars are "very worrisome" in that they could
harm her own efforts to get grant money. Says Hess, "Certainly one of my
motivations is I don't want money from adult stem-cell research being
pushed into embryonic, though it's already starting to happen."
Activists such as Christopher Reeve have it backward when they say that
restrictions on ESC research funding will prevent him from walking again.
ASC studies already have enabled quadriplegic animals to walk again, and
human trials should be right around the corner. But the chance of ESCs
helping people such as Reeve in the next 10 years is practically nil.
Reeve should know about this: Many of the amazing ASC studies, including
Ira Black's, have been funded by something called the Christopher Reeve
Paralysis Foundation.
Moreover, to the extent that breakthroughs with ASCs are confused with ESC
technology, it harms public support for ASC research. ESC propagandists
are hoping for a seesaw effect; that by exaggerating ESC research and
denigrating ASC research they'll push up their side of the board. But, to
the extent they succeed, they're only delaying the stream of miracles
coming from adult stem cells.
Michael Fumento is author of BioEvolution: How Biotechnology Is Changing
Our World, which has just been published by Encounter Books of San
Francisco.
Note: When fertilization initially takes place, whether within a fallopian
tube (in vivo) or in a petri dish (in vitro) it forms a single-cell embryo
called a zygote. The zygote divides progressively into a multicell embryo.
After about five days, the embryo contains many cells with a cystic cavity
within its center and is called a "blastocyst." If this blastocyst
implants into the uterus and continues to develop, it becomes a fetus. But
this is also the stage at which the individual cells become viable for use
in ESC experimentation. "Blastocyst" is not to be confused with "blastocyte,"
which is simply another term for an ESC.
+++++++++++++++++++++++++++++++++++++++++++++
Copying of this material is free for non-commercial educational and
research use. Unless explicitly stated, copyright of this material is
owned by the author and/or sponsoring organization, and/or newswire
services.
|