A vs E, the Stem Cell Debate

I have been relentlessly supporting attention on Adult Stem Cell Research as opposed to
Embryonic Stem Cell Research, partly because Kyle was opposed to ESC, and
partly because there are worrisome issues to me that continue on to the
cloning debate. This article I found from www.insightmag.com is a great way to start (hat tip: kill as
few patients as possible) to begin my argument, which I will continue further.

The Stem Cell Cover-Up

Posted
May 24, 2004

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 gnat that 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.