http://www.americanprogress.org/site/pp.asp?c=biJRJVF&b=40349

Think Again: Misreporting Stem Cell Research

by Chris Mooney
March 25, 2004

Last week some journalists thought they had found a juicy story, full of
conflict: The military was doing an apparent end run around the Bush
administration's restrictive policy on stem cell research. "The Pentagon
has granted $240,000 to a Swedish team for embryonic stem-cell research
linked to Parkinson's disease ... despite U.S. government limits on
stem-cell research," reported Reuters on March 17. The president may have
curtailed research "in this country," noted MSNBC host Keith Olbermann in
reaction to the news, but he "never mentioned Sweden." "Let's see if we got
this straight," added the Dallas Morning News. "An injection of federal
money triggers the restrictions on [stem cell] research at American
universities ... So the Pentagon finds a university in Sweden that is happy
to conduct the research."

Um, no. The supposed "Sweden loophole" - a distinction between using
federal funds for American university stem cell research and research
abroad - is nonsense. Despite the misleading Reuters report, the Pentagon
was in fact supporting research on two stem cell lines that had
been derived by Swedish researchers before the president's August 2001
deadline and were therefore eligible for federal funding. This non-story
created considerable confusion, however, and underscores key deficiencies
in the way journalists have covered stem cell and cloning issues in the
United States. These failings aren't trivial: They've often helped to mask
serious flaws in the president's policies.

In general, reporting on biotechnology issues tends to focus on conflict
and drama and to be highly fragmentary or episodic, notes Matthew Nisbet,
an assistant professor of journalism and communication at the Ohio State
University who studies press coverage of the stem cell and cloning
controversies. Journalists in the major media will often latch onto these
issues suddenly and when drama can be found - "UFO cult claims cloned
baby," to take a prominent example from December of 2002 - and then drop
them again just as quickly. This stop-again, start-again coverage pattern
both alarms the public and fails to educate. Moreover, it creates a
situation in which important developments that are technical in nature get
ignored, while easily graspable controversies or even pseudo-controversies
(the Pentagon story, various human cloning claims) get magnified.

Here's how this helps Bush. It's abundantly clear by now that the
president's stem cell research policy has been a failure. Despite
Bush's promise of "more than 60" stem cell lines for research in August
2001, even now only 17 are available for shipping to scientists. At least
one prominent researcher has left the country in despair; states like
California and New Jersey are moving in to fund research to make up for the
lack of federal money; and universities, too, are setting up privately
funded centers to nurture science that has been stifled by Bush's policy.
All of this seems particularly inexcusable given revelations that Bush made
his "more than 60" lines claim, which startled experts, on the basis of
inadequately vetted scientific information. The president appears to have
been more interested in outlining a victorious "compromise" than in setting
good policy.

But despite ample evidence of this failing, Bush has never really been
held accountable by the press. Consider the NIH's disclosure, earlier this
month, that only 23 lines might ever be available under Bush's policy.
This was, arguably, the biotech equivalent of failing to find Saddam's WMD.
Suddenly the president's proposed "compromise" - "to explore the promise
and potential of stem cell research without crossing a fundamental moral
line," as he put it - stood naked in all its inadequacy, its supposed
scientific foundations thoroughly undermined. Sure, there had been a steady
stream of criticism of Bush's policy, but now we had numbers - from NIH, no
less. Yet despite a story from the reliable Rick Weiss of The Washington
Post and a few other journalists, the media largely ignored the news. The
23 lines revelation "didn't get a lot of play at all," Nisbet notes.

How is this possible? Well, the number of stem cell lines is a technical
issue. And the complexities of stem cell policy - involving the dispersal
of stem cell lines across the globe, conflicts over intellectual property
rights, problems of line contamination, debates over the relative promise
of adult stem cells versus embryonic stem cells, and so forth - are
science-y and off-putting. Considerable drama may have lurked beneath the
surface of the "23 lines story": the news undermined one of the president's
first and most prominent policy decisions and arguably contributed to his
"credibility gap." But few reporters seemed prepared to wrap their minds
back around the complex stem cell issue, which hasn't been covered with any
real intensity since before 9/11.

Matters get even worse when stem cell research meets cloning, with which
it tends to get confused in the public mind thanks to the press. "In 2002,
30 percent of the time when stem cell research is covered, it's covered in
the context of the cloning issue," says Nisbet. That's troubling for the
following reason. The prospect of human cloning creates strong negative
connotations for the public, conjuring up the specter of armies of
look-alikes marching in lock-step. These concerns - valid or otherwise -
have nothing to do with the stem cell issue, but have been allowed to rub
off on it. Such confusion helps the president and pro-life interests, as an
issue that truly turns on whether abortion politics should block research
gets overshadowed by speculative concerns about the arrival of a Brave New
World.

A similar confusion has infected the related issue of research cloning, or
"therapeutic cloning." Scientists hope that by deriving stem cells from
cloned embryos, rather than embryos discarded from in vitro fertilization,
they will be able to circumvent possible immune system rejection issues as
they seek new treatments. But though there are good scientific reasons for
doubting whether cloned embryos actually have the potential to develop into
normal human beings if implanted in wombs, conservatives and President Bush
have consistently sought an outright criminal ban on all forms of cloning,
reproductive and therapeutic alike. This strategic yoking leverages a moral
fear of human cloning against scientific research that may never actually
lead to that outcome. But yet again, the press's consistent failure to
educate on these issues - and its tendency to create panics by covering
fringe groups claiming to have produced clones - confuses the science and
thus bolster's the president's policies.

Science issues aren't easy to cover, especially when they blend with
politics. But inconsistent, seat-of-the pants reporting has severe
consequences. There are countless parents out there whose kids have
juvenile diabetes, and for whom every passing day brings them closer to the
possible onset of serious complications. Many of these parents have
latched onto stem cell research as the best hope for a cure. In such a
situation, the last thing the press should be doing is providing a fig leaf
for the president's policies.

Chris Mooney (www.chriscmooney.com), a freelance writer living in
Washington, D.C., is writing a book about the Republican Party and science.

http://www.boston.com/news/nation/articles/2004/03/06/presidents_panelskewed_facts_2_scientists_say/

President's panel skewed facts, 2 scientists say
By Gareth Cook, Globe Staff, 3/6/2004

Two scientists from President Bush's top advisory board on cutting-edge
medical research yesterday published a detailed criticism of the board's
own reports, and said the board skewed scientific facts in service of a
political and ideological cause.

The authors -- one is a member of the President's Council on Bioethics and
the other was fired from the council over a week ago -- have accused the
council's chairman, Dr. Leon R. Kass, of ignoring their scientific advice
and refusing to include in the board's last report some information that
would challenge Bush's restrictions on stem cell research.

Their allegations mark the sharpest public split yet within the council,
formed in 2001 to guide US policy through the increasingly difficult
ethical terrain of such fields as cloning, in-vitro fertilization, and
embryonic stem-cell research.

The authors of the critique published yesterday were two of only three
full-time scientists on the council. They said the council's last report,
"Monitoring Stem Cell Research," did not make clear that a wave of recent
scientific research has cast doubt on the potential of adult stem cells --
a type of cell that Bush held up as a promising alternative when he
announced his restrictions on the use of embryonic cells.

Although the council is supposed to provide impartial advice to Bush, one
of the scientists said yesterday that its reports seemed to be driven by a
preexisting agenda and did not accurately portray the scientific
underpinnings of the ethical issues the council was grappling with.

"There is always this strong implication [in the reports] that medical
research is not what God intended, that there is something unnatural about
it," said Elizabeth H. Blackburn, a highly regarded biologist who was fired
from the panel last Friday. "We had a great many comments on the report,
and they would just make a little changes that didn't fully address them."

A spokesperson for Kass said that he had no comment on the allegations and
that the scientific comments of Blackburn and Janet Rowley, a University of
Chicago biologist who cowrote the critique, are adequately represented in
the council's reports.

Their critique was published online yesterday by the journal PLoS Biology.
It adds to growing criticism from scientists that the Bush administration
is manipulating the scientific advice it receives on politically charged
issues, ranging from climate change to mercury contamination. Last month,
the Union of Concerned Scientists issued a statement, signed by more that
60 Nobel laureates, that alleged the administration has manipulated
scientific findings to a degree unprecedented in recent White House history.

The critique also adds to the drama of what is becoming a cause for some
biologists: the firing of Blackburn. Blackburn, a member of the National
Academy of Sciences and the Institute of Medicine, is often mentioned as a
likely candidate for the Nobel Prize for her work in cell biology. But
eight days ago, she was told the council had new priorities and she was
abruptly fired by a White House official. Kass, the council's chairman, did
not tell her she was going to be asked to leave and has not spoken with her
since, Blackburn said yesterday.

But shortly before she was fired, she showed him the text of yesterday's
critique and told him she had submitted it for publication. At the same
time Blackburn was fired, another council member was asked to leave,
medical ethicist William F. May of Southern Methodist University.

The firing has drawn attention in the scientific community and has been
criticized by some politicians.

"We have diseases that can be cured, and we have a president who has
kicked two people off the commission because they happen to think we ought
to be doing stem cell research and other kinds of research, and he doesn't
want that outcome," said Senator John F. Kerry yesterday through a
spokesman. "It is clear that the administration has no respect for
science."

The critique published yesterday focuses on two reports issued by the
council, one issued in October titled "Beyond Therapy: Biotechnology and
the Pursuit of Happiness," and another issued in January titled "Monitoring
Stem Cell Research."

The two scientists' critique, entitled "Reason as Our Guide," alleges that
the "Beyond Therapy" report unfairly characterizes research into prolonging
healthy life as being dominated by scientists who are driven by the goal of
immortality. The report, they write, "falls short of explaining the serious
challenge of preventing and curing age-related disease to extend health --
very different from attempting immortality."

Blackburn, a professor at the University of California at San Francisco,
said that she had submitted a letter to the journal Science, outlining the
problems with that report, but that Kass ordered her to withdraw the
letter, which she did.

In another section of their critique, Blackburn and Rowley list a series
of problems with the stem cell report. The cumulative effect of the
problems, Blackburn said, is to overstate the current research promise of
adult stem cells and play down the potential of embryonic stem cells, which
are created by destroying a human embryo when it has reached a ball of
about 100 cells. To its critics, embryonic stem-cell research amounts to
taking a human life -- an objection that does not apply to the adult cells,
which can be extracted from a person's body without harm. In 2001, Bush
declared that the federal government would not fund research using human
embryonic cell lines that had not been created before his statement.
Michael S. Gazzaniga, a neuroscientist at Dartmouth College who is the only
other full-time scientist on the council, said yesterday that he was "very
disheartened" that Blackburn had been fired, but that he had no plans to
quit the panel. Asked about the new critique by Blackburn and Rowley, he
said, "I 100 percent support what they are trying to do," but declined to
elaborate.

The report published yesterday is available at www.plosbiology.org.
Gareth Cook can be reached at cook@globe.com

Hilary Rose
The Guardian
February 16, 2004

Here we go again. Reading the excited claims for the medical benefits
likely to accrue from the Korean veterinary researchers' success in
growing cloned human pre-embryos, one is entitled to feeling a certain
deja vu. Heading the list were those old favourites, treatments for
Parkinson's and Alzheimer's disease. There really needs to be a phrase
to describe this researchers' equivalent of the old charge against
doctors of shroud waving.

After all, only a few weeks back we were told that the planned primate
research centre in Cambridge was crucial in the search for treatments
for just the same diseases. The truth is that no one knows if stem cells
- the intended end product of therapeutic cloning - will have such
curative powers, still less the solution to the spinal injuries
Christopher Reeve was hoping for in Friday's Guardian. The right way to
find out - the way biomedical research normally proceeds - is to try the
methods first with laboratory animals. And so far their success, even
for the best-understood condition - Parkinson's - has been limited. This
isn't to say that stem cells aren't a promising technology. But even
then one would need to be very sure that the same results could not be
carried out with adult stem cells without the need to clone embryos.

What is clear is that the rush to experiment with human embryos is, to
say the least, premature, driven more by the lust for scientific glory
than a clear sense of the medical imperatives. As the procedures
involved in therapeutic cloning are almost identical to those needed for
reproductive cloning, the Korean achievement brings that closer, too.
This inexorably opens the doors to those whom Suzi Leather, the
chairwoman of the Human Embryology and Fertilisation Authority, calls
"cowboy cloners". It is this weakness in the medical case for human
therapeutic cloning that throws the moral issues into such sharp relief.
So why shouldn't we be reassured when she tells us that the Korean
research was "ethical"?

The project was accepted by the Korean ethical committee, but ethical
standards are by no means uniform, so for the one American member of the
team such work would be illegal in several US states. And then there is
the special problem of Britain, which pushed earlier and harder for stem
cell research than most other countries and now has the most liberal
research regime. Just how ethical are we? The Human Genetics Commission
has wide public representation, but on the hot issue of cloning the
government was certainly not risking such public debate. Instead, it set
up a separate expert committee that concluded that stem cell research on
specially created embryos was acceptable.

W here are the embryos to come from? In the US, discussion about the
risks to women is transparent. But the UK experts' report on stem cell
research speaks blandly of "individuals whose eggs or sperm are used to
create the embryos" to mask the differential bodily risk for women and
men. When a woman and her partner go for IVF, she has to decide if the
discomfort and risk involved in having the hormonal treatment and
surgery are worth the chance of a child; all he has to do is masturbate
into a test tube. Deciding to accept some risk for clear benefit is at
the heart of medical ethics. It is a little harder to see how
researchers asking women to accept such invasive procedures for no
personal benefit are acting ethically. If things go wrong (and they do
in up to 20% of cases) IVF procedures can result in severe health problems.

How did our British experts manage to ignore this gender problem? The
answer is embarrassingly obvious - the stem cell committee of 14
included only one woman. By contrast, the House of Lords select
committee discussion of stem cells was both less dominated by technical
experts and much more cautious. It wrote: "The committee believes that
embryos should not be created specifically for research purposes unless
there is a demonstrable need." The Lords committee consisted of six
women and four men, and at least one of them knew her way around nursing
and midwifery.

When is British public discussion going to face the fact that
reproductive engineering does not impact evenly on the genders, and that
the ethical discussion of bioethics demands fair gender representation
on advisory committees? There is a minister who is supposed to look
after women's interests, but it seems that she has either gone to sleep
on the job or doesn't see that the direction of biomedical research
could be part of it.

Complacency about British ethical standards is no substitute for
effective control. The government thought that it had ruled out
reproductive cloning, and it took a legal challenge from the Pro- Life
Alliance to demonstrate otherwise. The problem of medical tourism by
would-be parents is trivial compared with the need to control the search
by biomedical researchers for countries with soft standards - whether
Britain or Korea.

-
Robt Mann
consultant ecologist
P O Box 28878 Remuera, Auckland 1005, New Zealand
(9) 524 2949

The article below confirms that human cloning is not likely to be viable
at present.

However, the problems with stem cells from clones are
obfuscated and the cancers and other problems ignored.

February 17, 2004 NY times
Specter of Cloning May Prove a Mirage
By STEPHEN S. HALL

A rose is a rose is a rose, even if - like many commercial plants - it
is essentially a clone. But is a normal human blastocyst, a microscopic
bubble of proto-life that forms about five days after sperm meets egg,
the same as a cloned blastocyst?

That may seem an arcane technical question in the debate about human
cloning, reignited last week with the announcement by South Korean
scientists that they had cloned a human embryo and harvested embryonic
stem cells from it. But scientists, politicians and bioethicists have
been grappling for years with the biological and moral subtleties
encapsulated by that tiny dot of tissue.

The future of human therapeutic cloning in this country ó the laws
governing it, the knowledge to be gained from it, the ethical costs of
doing it and the medicines it might eventually bestow ó may hinge on how
society views that question.

In last week's report in the journal Science, researchers at Seoul
National University described how they had created some 30 cloned human
blastocysts in order to harvest human embryonic stem cells. Such a
procedure has raised moral concerns, not only because it requires the
destruction of the embryo to gather the cells, but because its mere
publication may provide technical guidance to several well-known
"cloning entrepreneurs" who have vowed to try human cloning, despite
widespread safety and moral concerns.

In response to the South Korean experiment, Dr. Leon R. Kass, chairman
of the President's Council of Bioethics, said, "The age of human cloning
has apparently arrived: today, cloned blastocysts for research;
tomorrow, cloned blastocysts for baby-making." Dr. Kass urged Congress
to pass a ban or moratorium on all forms of human cloning. Several
lawmakers called for just such a ban on all human cloning research.

But it's unclear how imminent that "tomorrow" actually is. While the
South Korean paper offers a new technical trick for creating a cloned
human blastocyst, it does not resolve any questions about how robust
that blastocyst may be for generating a healthy, normal human being.

"There's no doubt that there's still an awful lot of work to be done
before anybody would feel comfortable that it could be done safely,"
said Dr. George Daley, a stem cell researcher at Children's Hospital in
Boston.

The South Korean group did not try to create a baby. The promise of
therapeutic cloning, still theoretical, derives from the following
premise. By introducing the DNA of an adult human cell into a human egg
whose nucleus has been removed, the resulting hybrid cell can be induced
to behave like a fertilized egg. Like a normal embryo, it begins its
development as a single cell, but it contains the genetic payload ó and,
presumably, the immunological identity ó of the adult patient.
Treatment, not children, is the ultimate point of the exercise.

But cloned embryos may not be genetically equivalent to normal embryos.
Dr. Rudolf Jaenisch, an expert on the genetics of animal cloning at the
Whitehead Institute for Biomedical Research in Cambridge, Mass., has
published studies showing that cloned mice are riddled with genetic
abnormalities. Those glitches suggest that a cloned embryo would have
"little if any potential to ever develop into a normal human being."

When an egg cell reprograms the DNA of an adult cell during a cloning
experiment, Dr. Jaenisch said, the process is probably incomplete ó
raising the possibility that genes in the cloned embryo are not
activated (or "expressed") at the right time, in the right amount, and
properly suppressed when not needed.

Gene regulation of this sort is especially significant in a class of
genes known as imprinting genes, which play a crucial role in fetal
development. "We think that 30 to 50 percent of imprinted genes are not
properly expressed in clones," Dr. Jaenisch said, "and imprinting genes
are mostly important for pre-natal development."

As a result, he said, the South Korean approach may be "useful for
therapy, but not useful for cloning." Dr. Daley, who with Dr. Jaenisch
published one of the first animal experiments suggesting the promise of
therapeutic cloning, said, "All of the concerns and risks of mammalian
reproductive cloning have not changed with this paper."

Paradoxically, however, scientists working in the area believe that the
same genetic glitches that might prevent an embryo from growing into a
genetically normal organism are unlikely to compromise the quality of
stem cells that might be harvested for medical use. "Cloned tissues are
not likely to have the same problems," Dr. Daley said, "but that's yet
to be proven."

In addition to being a notoriously inefficient procedure, animal cloning
has produced many animals with conspicuous developmental problems, like
respiratory illnesses and overly large placentas. Dolly the cloned sheep
suffered from premature arthritis before dying last year. Such genetic
dysfunction is one reason for nearly unanimous scientific opposition to
reproductive cloning. As Dr. Daley put it: "As a scientist, I would be
willing to support a ban on reproductive cloning, if it allows us to
pursue legitimate therapeutic research. That is the most rational way of
approaching the debate."

But Dr. Jaenisch also made a distinction between cloned embryos and the
kind of blastocysts formed during normal reproduction, including embryos
fertilized in vitro. "When you really think about an I.V.F. embryo that
rests in a deep freeze, it only has three fates," he said. "It can be
destroyed, it can be implanted into a woman or it can be converted into
embryonic stem cells. When you make embryonic stem cells, you do destroy
an embryo, and that is an ethical issue.

"Cloned embryos also have three fates. "They can be destroyed, they can
be used to make normal embryonic stem cells tailored to the needs of
patients, but they cannot make a normal baby. In my opinion, the
destruction of a cloned embryo to make embryonic stem cells poses less
ethical problems than the destruction of frozen embryos in the I.V.F.
clinic."

Dr. Thomas H. Murray, president of the Hastings Center in Garrison,
N.Y., says this scientific distinction has moral import. "What are the
ethical implications if embryos created in this way are not viable, or
severely impaired?" he asked. "If Rudy Jaenisch is right, if embryos
created by cloning are a fairly abnormal ball of cells, that would
compel us to think very hard about what moral meaning to attach to such
an entity."

Such a scientific distinction, Dr. Murray also noted, could "complicate"
a split in the anti-abortion movement that emerged several years ago
during the debate over stem cell research and cloning. Several prominent
abortion opponents, including Senator Orrin G. Hatch, Republican of
Utah, supported federal financing for stem cell research; Mr. Hatch has
also co-sponsored legislation allowing therapeutic cloning while
prohibiting reproductive cloning.

In fact, the biological distinction between cloned embryos and normal
embryos came up for discussion two years ago at the President's Council
on Bioethics. Dr. Paul McHugh, the former head of psychiatry at Johns
Hopkins University School of Medicine, floated the notion that a cloned
embryo was distinct ó in creation, composition and reproductive intent ó
>from a normally formed embryo. He coined the word "clonote" to
distinguish it from "zygote," the single-celled embryo that results from
fertilization.

"If you take the point that the clonote is something different, it's
something manufactured rather than begotten, then you would want to
study, use its best potentials for humankind and not let its potentials
for error and slavery appear," he said at the time.

Despite the renewed calls last week for a ban on all forms of cloning,
including therapeutic cloning for medical research, even the Bush
bioethics council split sharply on the issue. In discussions leading up
to the panel's July 2002 report, "Human Cloning and Human Dignity: An
Ethical Inquiry," the committee failed to muster a majority in favor of
a blanket ban on both therapeutic and reproductive cloning. Only 7 of 17
voting members supported a complete ban; 3 others supported a
moratorium. Indeed, the panel's public discussion leading up to the
report revealed considerable sentiment in favor of therapeutic cloning,
as long as it was properly regulated.

The most provocative aspect of the South Korean research, in Dr. Daley's
opinion, was something that was not even included in the paper, but was
revealed by several of the scientists at a news conference last
Thursday. Dr. Woo Suk Hwang and Dr. Shin Yong Moon said that when the
researchers tried to use the DNA from male adult cells or cells from
females unrelated to the egg donors, they failed to create any embryos.
The only successes in their cloning experiments came from the use of
so-called cumulus cells, the adult cells that typically surround a
maturing egg cell in a woman's ovarian follicles.

The failure of the other cells to work, Dr. Jaenisch said, merely
underscores how much research remains to figure out the best adult cells
to use for therapeutic cloning. Whether making human medicines or human
babies through cloning, in other words, "tomorrow" may still be a long
way off.

http://truthout.org/docs_04/012704G.shtml
http://truthout.org/docs_04/printer_012704G.shtml

What's the Beef?
By Tim King
The Christian Science Monitor

Tuesday 22 January 2004

The FDA weighs whether to allow meat and milk from cloned animals to enter
the food supply. Opponents fear the impact.

LONG PRAIRIE, MINN. - In the beginning, there was Dolly. Since then, one
by one, beef and dairy cattle, pigs, and goats have joined the Scottish
sheep in a 21st century ark of cloned farm animals.

But while cloned animals have become common in the lab, they have yet to
make it to the dinner table. That could change if the Food and Drug
Administration overturns a ban on the consumption of cloned livestock. In
a few years, their meat or milk could become a regular staple on America's
menu.

The results could be significant: higher-quality meat and dairy
products, foods engineered to be more nutritious, and possibly lower
grocery prices, thanks to the arrival of more productive animals. The
infant farm cloning industry is chomping at the bit to commercialize its
research.

But consumer and animal advocates worry about the impact that cloning
could have on human health, not to mention the animals themselves. There
is no evidence "that food from cloned animals is safe," said Carol Tucker
Foreman of the Consumer Federation of America in a statement. "The FDA has
only limited data on the composition of food from cloned animals, and
there have been no feeding studies to see the impact of long-term
consumption. All of the data come from groups who support animal cloning."

So far, the signs for the industry look positive. Last October, the FDA
said that food products from cloned livestock were essentially the same as
those from conventional animals. It is working on a risk-assessment plan
that, for now, indicates there is little risk to humans who eat cloned
livestock. The release of the final assessment has yet to be scheduled.

Only a few hundred cloned cattle currently live in the United States,
mostly on research farms, so a repeal of the ban would have little
immediate effect on the food supply. However, dropping the barrier would
dismantle a hurdle that has kept the industry in the starting blocks,
proponents say.

"There's no question that the voluntary ban ... is holding the
development of this business back," says Don Coover, a rancher from
Galesburg, Kan., and owner of SEK Genetics, a cattle-genetics company with
cloning partnerships. He has financed several cloning projects, including
six clones of the high-performance bull, Full Flush. Full Flush's calves
are healthy 2-year-olds and have increased in value more than five times
their original production cost of $20,000, he says.

Cloned cattle like them could be used to breed uniform, high-quality
offspring. "You could make animals with less fatty meat or more nutritious
milk," says Lisa Dry, communications director of the Biotechnology
Industry Organization in Washington. "Or they could be more resistant to
diseases, which could make them safer for humans to eat."

Mr. Coover, who sells bull semen for artificial insemination, says there
is a growing demand for that product from top-quality bulls. "There's
quite a lot of interest in buying semen from the clones, but we're telling
people that we're not going to do that," he says. "It's the obligation of
the FDA to make a decision that is in the best interest of ... the
producers and the broader public."

The FDA's preliminary decision, which is part of the formal
risk-assessment process and thus not final, is based on findings from a
National Academy of Sciences (NAS) report. Although the NAS study,
commissioned by the FDA, said food from cloned animals was probably safe,
it did express reservations.

"Limited sample size, health and production data, and rapidly changing
cloning protocols make it difficult to draw conclusions regarding the
safety of milk, meat, or other products from ... cloned [animals]," the
NAS reported in August 2002.

But with cloning technology clipping along at a thoroughbred's pace, the
FDA decided last fall to release 11 pages of its risk assessment, which
considers cows, sheep, pigs, and goats. "Food products derived from animal
clones and their offspring are likely to be as safe to eat as food from
their non-clone counterparts, based on all the evidence available," FDA
officials reported in October. "These scientific findings also showed that
healthy adult clones are virtually indistinguishable from their
conventional counterparts."

However, the FDA has acknowledged that it will explore animal-welfare
issues. Research has shown that the cloning process severely affects the
genetic makeup of animals and can cause clones to suffer. The Humane
Society of the United States, for one, is deeply concerned about the
ethical implications of cloning.

"Deaths and deformities in cloned animals are the norm, not the
exception, and these studies make plain once again that these creatures
are suffering terribly in the process," says Wayne Pacelle, senior vice
president of HSUS. "There is no societal value to this. This is just
science run amok in the service of the further industrialization of
agriculture."

The main method of cloning involves taking the nucleus from a cell of
the animal to be cloned and placing it in an egg that has had its nucleus
removed. A University of Missouri study on cloned pigs, according to HSUS,
reported that "out of 10 born, 5 died or were destroyed by researchers due
to defects such as heart failure, lameness, and anemia."

Jorge Piedrahita and researchers at North Carolina State University's
College of Veterinary Medicine announced last month that they had cloned
two Duroc pigs. "Certain genes were dis-regulated or damaged," Mr.
Piedrahita reported.

And in 2002 Rudolf Jaenisch, a researcher at MIT, reported that cloned
mice have hundreds of abnormal genes. Some have a genetic tendency toward
obesity.

The NAS has pointed out that ill clones would probably be more stressed
as they reach maturity, and it suggested the animals might shed more
pathogens in their manure. That would increase the potential of
contaminated carcasses entering processing plants and, later, the food
supply.

"While some forms of animal cloning may have inherent benefits, others
are hard to justify," said the Consumer Federation's Ms. Foreman in a
statement. "The FDA needs to make, or ask another government agency to
make, some decisions about appropriate uses of cloning."

The Making of a Human Clone
(PDF Format)
7 days inside a maverick embryo lab
Wired - January 2004

http://www.newscientist.com/news/news.jsp?id=ns99994492

'Humanised' organs can be grown in animals

19:00 17 December 03

It's bad news, says your doctor. Your liver is failing. So he extracts stem
cells from your bone marrow and injects them into a sheep fetus while it is
still in the womb. When the sheep is born, much of the animal's liver will
consist of your own cells - ready to be harvested and given back to you.

This dream therapy is still years off, if it happens at all, but the first
steps have already been taken by a team led by Esmail Zanjani at the
University of Nevada, Reno. "Esmail has some pretty startling results," says
Alan Flake of the Children's Hospital of Philadelphia.

Zanjani's team hopes the animal-human chimeras they are creating will one
day yield new cells genetically identical to a patient's own for repairing
damaged organs, and perhaps larger pieces for transplantation.

It might even be possible to transfer whole organs, since in some cases
having at least a partly human organ would be better than a purely animal
xenotransplant. Immune rejection of the animal portion would still be a
problem, but it is not insurmountable, says Flake. "I don't think that in 10
to 15 years that's out of the question."

Growth factors

If perfected, the technique could overcome some of the big stumbling blocks
facing researchers who want to make tissues and organs for implants. It
might yield significant quantities of just about any kind of cell or tissue,
for instance, with no need to fiddle about with different culture conditions
or growth factors.

Instead, the host animal's own developmental program guides the injected
human stem cells into their final roles. "We take advantage of the growing
nature of the fetus," Zanjani says.

It would also allow doctors to obtain immune-compatible cells without having
to create human embryos by therapeutic cloning. Human cells could be
separated from the animal ones simply by modifying existing cell-sorting
machines.

Providing the method really does produce normal human cells, they would not
be rejected. And any stray animal cells would be killed off by the
recipient's immune system.

Of course, the idea of using part-human, part-animal chimeras as living
factories for producing cells or organs raises a host of ethical and safety
issues. There is the risk of transferring animal diseases to humans, for a
start. And the creation of such chimeras has long been controversial. Is a
sheep with human cells making up part of its brain no longer just a sheep?

Stem cell jab

Zanjani's original goal was to see if unborn children with genetic defects
could be treated by injecting healthy stem cells into the fetus. This is
still his main aim, but while doing animal experiments he realised the
technique could also be used to grow "humanised" organs.

The first hint this might work came from work done by Flake a few years ago
(Nature Medicine, vol 6, p 1282). He showed that when human mesenchymal stem
cells extracted from bone marrow are injected into sheep fetuses, the human
cells become part of the heart, skin, muscle, fat and other tissues. But the
numbers of human cells were very low. Zanjani's team has now managed to
produce sheep-human chimeras with a surprisingly high proportion of human
cells in some organs. According to results presented at a conference earlier
in December, in some cases between seven and 15 per cent of all the cells in
the sheep's livers are human.

The human cells must be injected around halfway through gestation - before
the fetus's immune system has learned the difference between its own and
foreign cells, so that the animal does not reject them, but after the body
plan has formed.

That ensures that the resulting animals look like normal sheep rather than
strange hybrids like the "geep", created by fusing the embryos of a sheep
and goat.

Clustering together

In some cases the human liver cells cluster together to form functional,
fully human liver units, says Graca Almeida-Porada of the Nevada team. These
units could be transplanted whole as auxiliary organs, says Zanjani.

What is more, human albumin - a blood protein produced by the liver - has
been detected in the host animals' blood. The work has been submitted for
publication.

Meanwhile, results of similar experiments on the heart will be published
early in 2004. "The type of stem cells we use make a lot of heart cells," is
all Zanjani will say about these experiments.

If he is right, it would be an important advance because it would open the
door to creating fetal heart cells for therapy. For example, a kind of fetal
heart cell called a cardiomyocyte has been shown to be especially good at
repairing hearts in rats or mice, but there is one big obstacle: at the
moment the only source of human fetal heart cells is human fetuses.

Robert Kloner, a heart expert at the University of Southern California in
Los Angeles, says an approach like Zanjani's would get around this ethical
issue.

Time and place

Zanjani says it might also be possible to grow a wide range of other
tissues, such as insulin-producing islet cells for treating diabetes. And he
hopes it will be possible to increase the proportion of human cells in
organs still further.

The team is now trying to identify subpopulations of stem cells that might
be better at producing one organ or another. Their results also hint that
the timing and site of the injection make a difference.

But all members of the Nevada team stress that the technique is years, if
not decades away from being tested in humans. For starters, it will be
crucial to make sure the human cells really are functional. Recent
experiments have suggested that some stem cells fuse with other cells when
injected, rather than forming normal heart cells or liver cells.

A key question is whether the human cells fuse with sheep cells, says Philip
Noguchi, head of the Center for Biologics Evaluation and Research at the US
Food and Drug Administration. It would not necessarily be the death knell if
the cells do fuse, but it would be important to know what problems it
presents, Noguchi says.

Zanjani is optimistic, however: with human cells making up such a large
proportion of some chimera organs, he thinks the sheep would die if these
cells were dysfunctional fused cells.

Lurking viruses

All the same, there is widespread opposition to xenotransplantation in
countries such as the UK and Canada. One big worry is that retroviruses
lurking in animal DNA could mutate into forms that infect people.

The US is more open to the idea, and a few clinical trials are under way,
but health concerns mean Zanjani's technique would be expensive to develop.

What is more, companies are unlikely to invest in the method because he has
not tried to patent it. And it could even be unpatentable: in 1998, the US
Patent Office declared it unlikely that it would grant any more patents on
part-human inventions.

Then there is the moral issue. Some people oppose the creation of all
human-animal chimeras on religious grounds, and many more would join them if
there were the slightest chance that sheep with human brain cells might be
more than just sheep.

Zanjani doesn't rule out the possibility entirely. "There is no way for us
to know," he says. "But at the level we're working with the animal, it's
still a sheep."

Sylvia Pagán Westphal, Boston

from Prof Joe Cummins

I frequently point out the danger of cancer in use of embryonic stem
cells in therapy. The fact that stem cell advocates from major US
universities do not mention cancer only means that such company
promotors are practising traditional american "pump and dump" -
stock promotion intending to take advantage of gullible investors.

December 3, 2003
Embryos and cancer
Early embryonic pluripotency gene controls malignant phenotype in germ
cells | By Cathy Holding

The POU transcription factor Oct3/4 maintains the pluripotent state of
inner cell mass cells "at the blastocyst stage of preimplantation
development" that develop into the fetus after implantation. Different
levels of Oct3/4 expression result in altered potential for a given
embryonic cell, and the more pluripotent a cell, the less ìmatureî it
appears in terms of epigenetic programming and gene expression profile.
Oct3/4 is also expressed in spermatogonia in the adult male, and levels
of expression again are correlated with the ìmaturityî of that cell.

Germ cell tumors (GCTs) account for a high proportion of malignancy in
young men, and in the November issue of Cancer Cell, Sharon Gidekel and
colleagues at the Hebrew University Hadassah Medical School report not
only that Oct3/4 expression is found almost exclusively in GCTs, but
also that the level of expression is related to the immaturity "and hence
the malignancy" of the tumor. They also demonstrated for the first time
that overexpression of Oct3/4 in a heterologous cell system confers
tumorigenicity to that line when it is subsequently injected into nude
mice, again with malignancy related to immaturity. Finally, tumor
regression was observed when expression levels of Oct3/4 were inhibited.
This suggests that Oct3/4 acts as an oncogene and could be a potential
therapeutic target for this type of germ cell malignancy (Cancer Cell,
4:361-370, November 2003).

Gidekel et al. used immunohistochemistry and demonstrated the expression
of Oct3/4 in all of 45 primary human GCTs and absence in all of 182
solid tumors from other sources. Embryonic stem cell lines previously
engineered to have differing inducible levels of Oct3/4 expression were
injected into nude mice to assess the effects of varying levels of the
gene on tumorigenicity and of induction and repression of expression.
Cells were transfected with Oct3/4 expression construct, and
tumor-associated properties such as anchorage dependence were tested in
the resultant lines.

"These results fit well with the growing body of evidence that links
cancer with genes and pathways that are required for normal embryonic
patterning. In many cases, cancer seems to be caused by the deregulation
of transcription factors that affect cell fate and proliferation...
These findings support the view that many molecular pathways that
underlie carcinogenesis represent aberrations of the normal processes
that control embryogenesis," the authors conclude.

"This study provides further evidence that deregulated expression of
homeobox genes, which occurs in many solid tumors, is functionally
relevant for carcinogenesis and highlights unique features that
distinguish homeobox genes from other cancer-promoting genes," writes
Cory Abate-Shen at the UMDNJ Robert Wood Johnson Medical School in an
accompanying Previews article in the same journal.

Links for this article
F. Cavaleri, H.R. Scholer, ìNanog: a new recruit to the embryonic stem
cell orchestra,î Cell, 113:551-552, 2003.
[PubMed Abstract]

H. Niwa et al., ìQuantitative expression of Oct-3/4 defines
differentiation, dedifferentiation or self-renewal of ES cells,î Nature
Genetics, 24:372-376, April 2000.
[PubMed Abstract]

S. Gidekel et al., ìOct3/4 is a dose-dependent oncogenic fate
determinant,î Cancer Cell, 4:361-370, November 2003.
http://www.cancercell.org/content/article/abstract?uid=PIIS1535610803002708

Hebrew University Hadassah Medical School
http://www.md.huji.ac.il/

UMDNJ Robert Wood Johnson Medical School
http://www4.umdnj.edu/rwjcweb/

C. Abate-Shen, ìHomeobox genes and cancer: New OCTaves for an old tune,î
Cancer Cell, 4:329-330, November 2003.
http://www.cancercell.org/content/article/abstract?uid=PIIS1535610803002770

Human fertility experiment prompts wrath

Babies made by cloning-type technique die prematurely

14 October 2003
HELEN PEARSON

The embryos contained nuclear DNA from one mother, and mitochondrial
DNA from another.

US doctors have created the first pregnancies using a controversial
technique related to cloning. The babies died before birth.

Other experts have condemned the procedure because the health risks are
unknown. "You'd find it hard to find people that support it," says
reproductive-medicine researcher Chris Barratt of the University of
Birmingham, UK.

James Grifo of New York University School of Medicine created and
implanted the human embryos in China, working with colleagues at Sun
Yat-Sen University of Medical Science in Guangzhou1. Grifo will discuss
the results today at the American Society for Reproductive Medicine's
annual meeting in San Antonio, Texas.

The team fertilized eggs from two women in test tubes. They then sucked
out the nucleus of one egg and injected it into the other, which they
had stripped of its own nucleus. The idea is that the second egg will
better direct the growth of an embryo.

Grifo's team implanted five embryos into a 30-year-old mother who had
already undergone two failed attempts at in vitro fertilization (IVF).
Three embryos grew large enough for doctors to hear their heartbeats.

After a month, doctors reduced the pregnancy to two for the mother's
safety, but one fetus died at 24 weeks and the other by 29 weeks.
Whether the process was responsible for their deaths is not known.

The technique - called human nuclear transfer - is outlawed in many
countries, including Britain and the United States. "It's extraordinary.
You wouldn't get away with it anywhere else," says IVF doctor Allan
Templeton of the University of Aberdeen, UK.

Templeton argues that there was no compelling reason for using the
technique on the woman, because further rounds of IVF might have worked.
"The clinical justification is extremely dubious," he says.

Grifo and his colleagues say that they hope to help women whose own eggs
are unable to undergo successful IVF, or who carry damaging mutations in
their mitochondrial DNA.

Close to cloning

Grifo's method comes close to human reproductive cloning, which is
banned in many countries. In cloning, the nucleus of an adult cell,
rather than of a fertilized egg, is injected into another egg so that
the embryo is genetically identical to its parent. Grifo's technique
creates embryos with genes from both mother and father.

Like cloning, critics warn, Grifo's method might damage or incorrectly
programme the mother's DNA. What's more, the embryos carry genetic
material from two mothers: nuclear DNA from one, and small packages of
DNA in the mitochondria from the other.

The clinical justification is extremely dubious
Allan Templeton
University of Aberdeen

The effect of inheriting DNA from two mothers is unknown. Proteins made
from the two sets of genes may be incompatible, perhaps even stopping
the embryo's cells working.

A handful of children have been born through a related technique, in
which one woman's eggs are pepped up by injections of the cell cytoplasm
and mitochondria from another, fertile woman's eggs. This technique is
also now outlawed in many countries.

References
Zhang, J. et al. Pregnancy derived from human nuclear transfer.
Fertility and Sterility, 80, Suppl. 3, S56, (2003).

http://www.lifesciencenz.com/news-detail.asp?newsID=5189

World News > Clone products okay to eat


Meat and milk from cloned animals are safe, the US Food and Drug
Administration (FDA) has concluded in a preliminary report intended to help
determine whether the agency should regulate such products writes Jack
Lucentini in The Scientist.com.

In advance of a public meeting that the FDA's Center for Veterinary Medicine
(CVM) will hold on the controversial subject Tuesday (November 4) in
Rockville, Md., an executive summary of the full report (which is expected
to be released later this year) was posted on the CVM Web site today
(October 31).

"Edible products from normal, healthy clones or their progeny do not appear
to pose increased food consumption risks relative to comparable products
from conventional animals," the executive summary said.

The findings may displease consumer and environmental groups that have
campaigned against the sale of food derived from cloned animals.

Industry groups, however, have worked to persuade the agency that the
products are safe. Companies including Advanced Cell Technology (ACT) of
Worcester, Mass., have given the FDA supporting data, Robert Lanza, the
company's vice president of medical and scientific development, said.

ACT has cloned more than 100 cows, Lanza told The Scientist, and "the great
majority appear to be happy, healthy, and normal." Most scientists believe
that cloned animals' progeny are safe to eat, Lanza added, and the progeny,
rather than clones themselves, are the ones likely to be eaten.

Officials at the Washington, D.C.–based Center for Food Safety said it is
too early to draw such conclusions. "The analysis and the data on potential
safety is not there yet," said Joseph Mendelson, the group's legal director.
"It's premature to market this stuff."

A National Academy of Sciences report produced last year at the FDA's
request said that there is no evidence that products from cloned livestock
are unsafe for consumption, but that more tests were needed.

There are already mixed data on the health and normalcy of cloned animals
and their progeny.

"Somatic cloning may be the cause of long-lasting deleterious effects,"
reported researchers with France's National Institute of Agronomy Research
in a 1999 Lancet paper. The calf they had cloned suffered lymphoid
hypoplasia and died on its 51st day from severe anemia, making it "the first
report of a long-lasting defect associated with somatic cloning," the
researchers wrote.

Researchers with Humboldt University in Berlin and other institutions
reported in the April 1, 1997, Current Biology that mice may transmit
genetic changes associated with nuclear transfer to their offspring. This
finding was "striking," the authors wrote, because these types of changes
(epigenetic modifications) are normally not believed to be heritable.

Lanza said the scientific consensus today is that indeed, they are not.
"Epigenetic differences are reset" to normal when cloned animals conceive,
he said. This is relevant to the food issue because consumers won't be
eating clones, but only their progeny, he repeated. Industry experts say it
would make no sense to eat clones themselves, since a cloned cow costs about
$19,000.

Lanza and colleagues reported in the November 30, 2001, Science that they
analyzed a series of 24 cloned cattle and found no significant rate of
abnormalities.

"We did not observe genetic defects, immune deficiencies, gross obesity, or
other drastic abnormalities cited by other researchers," they wrote. "It
remains to be determined whether these abnormalities occur in other species
and/or are due to differences in nuclear transfer techniques." Two clones
also gave birth to normal-appearing calves, they noted.

Regarding cloned animals' health, the new executive summary said that
cloning "can pose an increased frequency of health risks to animals involved
in the cloning process, but these do not differ qualitatively from those
observed in other ARTs [assisted reproductive technologies] or natural
breeding."

Michael Appleby, the Humane Society of the United States' vice president for
farm animals and sustainable agriculture, said FDA officials seem to be
focusing too narrowly on food safety while overlooking ethical
considerations.

"That may be the limit of their purview of the subject, but it is clearly
not the limit of the relevant questions that can be asked," he said. For
instance, he said, society should consider the many embryos that die as a
result of cloning.

Also, "cows have been selected for milk production for so long, they carry a
huge weight of milk, which causes them leg problems and mobility problems,"
Appleby said, and compounding the problem, cloners would select among even
these successful milk producers for the most productive.

All this is "monumentally unnecessary," given the low food prices this
country already enjoys, he insisted.

The FDA has asked companies that clone animals not to introduce them, their
offspring, or their food products into the human or animal food supply until
the agency has evaluated the products' safety.

"We're waiting on the government to say this is going to be okay to use,"
Donald Coover, owner and manager of SEK Genetics in Galesburg, Kan., said.
Coover has already raised several bull clones in order to sell their semen.
"Financially, this is going to be a fairly big deal."

Source: The Scientist.com 1 November 2003