The Stem Cell Cover-Up

[Guest guest]

The Stem Cell Cover-Up

By Fumento

http://www.fumento.com/biotech/stemcell.html

Insight on the News, May 16, 2004

Copyright 2004 Insight on the News

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, 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.

Activists such as Reeve have it backward when they say

that restrictions on funding for embryonic stem-cell research will

prevent him from walking again.

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 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, 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.

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 Wood

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 loo

– 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 f

Mengele or of 's Dr. enstein.

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

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 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 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.

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.

Read Fumento's additional work on biotechnology.

Fumento is the author of numerous books. His book,

BioEvolution: How Biotechnology Is Changing Our World, was published

in 2003 by Encounter Books.