Hwang, ashamed, faces reporters
Nature: Published online: 10 January 2006;
Verdict: Hwang’s human stem cells were all fakes:
Landmark papers shown to be fraudulent, but Snuppy turns out to be a real cloned
university announced damning results in a press conference today.
SEOUL The results are
in. The university committee looking into scientific misconduct in the
laboratory of South Korean cloner Woo Suk Hwang announced on 10 January that his
2004 claim to have cloned a human embryo was fake. But his Afghan hound Snuppy
is a real clone.
finally confirms the gravest suspicions of Hwang’s work with humans. There are
two papers in which Hwang’s group claimed to clone human cells - a 2004 article
that describes the first cloned embryo and derivation of a stem-cell line from
it (W. S. Hwang et al. Science 303, 1669-1674; 2004), and a 2005 article that
claims the establishment of eleven ‘patient-specific’ stem-cell lines (W. S.
Hwang et al. Science 308, 1777-1783; 2005). Both have turned out to be complete
and deliberate fakes.
“Such an act is
nothing other than deception of the scientific community and the public at
large,” concludes Myung Hee Chung of Seoul National University (SNU), who headed
With the 2005 paper
already discredited in the panel’s interim report (see Nature 439, 8; 2005),
Chung’s statement focused on the 2004 paper. DNA fingerprinting tests carried
out by three laboratories found that the genetic material of the supposedly
cloned human cell line, NT-1, did not match that of the donor. Nor did it match
any of the stem-cell lines from the in vitro fertilization (IVF) embryos of
MizMedi Hospital, which were the source for the faked data in the 2005 paper.
revealed that mitochondrial DNA from the cell line matched one of the egg
donors, but the DNA inside the cells’ nuclei varied at several locations. The
committee concluded that the line was derived by parthenogenesis - where the
single set of chromosomes in an egg develop as if it were fertilized. The images
and data in the paper that showed perfect matches were fabricated.
The committee also
found that Hwang worked with a staggering number of eggs - 2,061 from 129 women
- despite claiming to have used only 242 eggs for the 2004 study and 185 for the
The findings are a
huge setback for therapeutic cloning - the idea that cloned embryos could be
used as a source of patient-matched stem cells to replace damaged tissues in a
range of diseases. Even using numbers of human eggs of which other researchers
can only dream, Hwang’s team was unable to derive such stem cells, and the field
is now left with no evidence that it is possible in humans at all (see Nature,
438, 1056-1059; 2005).
The committee did find
that Hwang succeeded in cloning human embryos to the blastocyst stage, from
which stem cells can be derived. But the success rate was just 10%, and they
were “in poor condition”. The only other group to have some success, Alison
Murdoch’s team at the University of Newcastle upon Tyne, UK, has cloned just a
single blastocyst (M. Stojkovic et al. Reprod. BioMed. Online 11, 226-231;
It is possible to
create embryonic stem-cell lines, insists Kevin Eggan, a researcher in the field
at Harvard University, Massachusetts. But no one will venture a guess as to when
it might be accomplished. “There are many unknowns,” says Eggan. “We don’t know
how many eggs will be needed and we don’t know how many women will step forward
in the way Hwang got his eggs - he seems to have coerced junior researchers into
donating - have stimulated an international debate over how eggs should be
obtained. Eggan expects to gain approval this spring to begin human stem-cell
cloning research, and he says his group will follow the US National Academies’
guidelines. These stipulate that egg donors should receive no payment.
Even when admitting
faked data, Hwang has maintained that his human cloning techniques are valid.
But most experts say they merely involve tweaks to previously known methods,
such as squeezing the nucleus out of cells rather than sucking them out with a
needle. “Besides some slight adjustments, there was really nothing new,” says
Teruhiko Wakayama of the Center for Developmental Biology in Kobe, Japan, who
created the first mouse clones in 1998.
Many experts conclude
that Hwang’s greatest achievement was Snuppy, the first cloned dog (B. C. Lee et
al. Nature 436, 641; 2005). The SNU investigators verified Snuppy’s identity as
a clone by proving that he had the same nuclear DNA as the skin-cell donor and
the same mitochondrial DNA as the egg donor - a conclusion that was confirmed on
10 January by Nature’s own investigation.
Dog ovulation produces
very immature eggs, so culturing them is difficult, even for basic IVF, says
Wakayama. “If it’s real, this is their greatest accomplishment,” he says. The
SNU committee also noted that Hwang - originally trained as a veterinarian -
showed greatest skill when it came to cloning animals, notably pigs and cows.
As Nature went to
press, however, the Munhwa Broadcasting Corporation, which originally accused
Hwang of faking his data, was about to air a television programme questioning
Hwang’s claim to have cloned a cow - the work that first shot him to fame in
South Korea. The SNU committee said it was unable to confirm whether the cow was
a clone because Hwang did not cooperate with them.
The committee, which
issued a 50-page report covering the investigation, stopped short of accusing
Hwang or other individuals on the team of deliberate fabrication. It deferred to
national prosecutors who will now look into legal aspects of the case and the
possibility of fraud. Hwang received huge funding from the Korean government for
his work, including an annual stipend of US$3 million, which he started
receiving this year as the country’s “supreme scientist”.
Scandal for Cloning Embryos: 'A Tragic
Turn' for Science
Last May, a stunning research paper in Science, one of the world's most
respected scientific journals, instantly changed the tenor of the debate
over cloning human embryos and extracting their stem cells. A team of South
Korean scientists reported in the paper that they had figured out how to do
this work so efficiently that the great hope of researchers and patients -
to obtain stem cells that were an exact match of a patient's - seemed easily
But that rosy future has been cast into doubt with the
statement last month by Dr. Hwang Woo Suk, who led the team that wrote the
paper, that it contained fabricated evidence. Questions have also been
raised about earlier research and a new debate has begun.
Scientists and ethicists caution that the full story is not in, but they
are staggered by how the research has unraveled so far.
"This is a tragic turn," said Laurie Zoloth, director of the Center for
Bioethics, Science and Society at Northwestern University. Stressing that
she considers Dr. Hwang innocent until proven guilty, she asked, however,
whether the edifice of stem cell research was built on sand.
"We depend entirely on the truthfulness of the scientific community," Dr.
Zoloth said. "We must believe that what they are showing us and what they
say has been demonstrated is worthy of our concern and attention."
The South Korean story, Dr. Zoloth added, raises questions about whether
the science is good. "Good as in true and real and morally worthy of our
funding," she explained. "That is so most especially in this twilight sort
of terrain with a lot of open questions that people disagree about. At least
we thought that the step-by-step slow technical achievements had placed the
science on a trajectory."
"Is this our version of W.M.D.?" Dr. Zoloth said.
A vocal opponent of cloning human embryos voiced a similar concern.
"Certainly, if these reports are true, it's a tragedy for science," said
Nigel Cameron, president of the Institute on Biotechnology and the Human
Future at the Illinois Institute of Technology.
He said the episode showed that stem cell research and cloning to create
human embryonic stem cells, "is a hype balloon and it's been pricked." Not
so, said the ethicist Arthur Caplan, an outspoken supporter of stem cell
research. "We know that in science, speed kills if you go fast, and that's
what the South Koreans did," he said. "It's also clear that they will do
whatever it takes to right this ship. At the end of the day, critics of stem
cell research will try to use this, but they won't get very far. People
bending the rules in other countries doesn't reflect badly on us."
The promise of cloned human embryonic stem cells remains, said Dr. George
Daley, a stem cell researcher at Children's Hospital in Boston.
"The goal is still there and the medical value is still largely
theoretical but no less than before."
Dr. Cameron, however, said the political implications of the South Korean
scandal are huge.
When it seemed that the South Koreans had taken a giant leap forward in
stem cell research, he noted, "we panicked into thinking that we have to
join in." Politicians and patient groups argued that cures were around the
corner if scientists could get the needed support. States poured money into
stem cell programs.
The collapsing South Korean claims, Dr. Cameron added, made him ask:
"Where's the beef? Where are those cures? Why is it that there is no private
money going into this research? The business community values it at zero."
Richard Doerflinger, deputy director of anti-abortion activities at the
United States Conference of Catholic Bishops, said that he has argued for
some time that the stem cell proponents were exaggerating the state of the
science and misleading the public about scientific accomplishments. They
promised cures that, if they ever came, would not come any time soon. But
Mr. Doerflinger said that when he tried to point out what he saw as
misleading claims, " no one would listen."
Now, he said, with the collapse of some of the South Korean scientists'
research, the situation may change.
"In one sense, this puts us back to where we were before May of 2005,
when there still was some uncertainty about whether this would work at all,"
Mr. Doerflinger said. "In another sense it does illustrate in my mind how
hype and ambition have gotten ahead of the science."
"How am I going to exploit it?" he said. "You don't have to. It's just
speaking for itself."
06:44:21 pm, Categories: Ethics and Science, Life Sciences, Medicine, 1416
Stem Cell Meltdown
That was the only word that came to mind in past weeks as the allegations and
admissions continued to mount over Woo Suk Hwang's announcement from last
summer that his lab had cloned embryonic stem cells from 11 human patients. It
was a breathtakingly exciting advance, one that seemed to hasten the day when
embryonic stem cells might be applied to treat or cure diseases. By any
reckoning, it was one of the stand-out scientific achievements of the year,
and it was enough to net Hwang a top spot on this year's Scientific American
50 list. But bit by bit, this milestone in stem cell technology has been
crumbling away, and it's beginning to look as though there's nothing left.
Let's review the history of scandal attached to this paper. First, the ethical
problems. It was alleged, and later confirmed, that some of the human egg
cells used in Hwang's experiments came from women working in the laboratory,
which was troubling because it opened at least the possibility that those
donations had been coerced. It was alleged, and later confirmed, that other
egg cells had come from paid donors, which at least currently is not preferred
practice. Hwang eventually admitted that he had known of these circumstances
for months but had nonetheless denied the allegations to protect the
reputations of his coworkers.
Then the rumors surfaced that the data in the paper itself were suspicious.
Several of the published micrographs, which were presented as showing
different sets of cells, upon closer examination turned out to be different
views of the same cells. This, at least, seemed to have an innocent
explanation: Hwang said the duplicates had been sent and published by mistake,
and Science acknowledged that the duplicate images were not part of Hwang's
original submission. But then researchers began to question why some of the
DNA profiles of the clones of cells were so very similar--they looked like the
same data because they lacked the expected level of experimentally induced
variation. Then coauthor Gerald Schatten of the University of Pittsburgh, who
had previously broken off his collaboration with Hwang in a very public split,
asked Science if his name could be retracted from the paper because he had
doubts about the paper's accuracy, and said cryptically that he had heard
"allegations from someone involved with the experiments that certain elements
of the report may be fabricated," to quote the New York Times.
And now another of Hwang's coauthors, Sung Il Roh, has said in interviews with
Korean media that Hwang admits that much of the evidence for cloning of the
stem cells was fabricated, and that he now would like to formally withdraw the
paper. Hwang, who is in the hospital for treatment of an ulcer, has not been
directly quoted to confirm this, but it's damningly suspicious that no one
from his camp seems to be stepping forward to deny it, either.
Flabbergasting. In six months, this work went from being one of the most
celebrated accomplishments of recent biotechnology--probably a strong
contender for future Nobel consideration--to what may become a legendary
scientific fraud akin to the Piltdown man.
(I haven't tried to link all the specific points above, but there's been some
thorough coverage of these developments by Nicholas Wade at the NYTimes, such
as here and here. Also, Glenn McGee at the American Journal of Bioethics Blog
has done an outstanding job in covering not just the facts of this case but
also what the ramifications for science might be: see here, here, here and
here, for example.)
So what will be the consequences of all these revelations? Well, for one, I
guess you could say that SciAm is asking for its ring back. But that's really
just the least consideration. Let's tick off some of the concerns and
question, big and small, still to be resolved.
How much of a colossal black eye will this scandal give to embryonic stem cell
work in general? I commented on that point previously, back when it looked
like Hwang's headaches all centered on the research ethics. But outright fraud
carries this to a whole new level. Frankly, I've been surprised that some of
the usually vociferous opponents of embryonic stem cell research haven't been
making more of a fuss about the Hwang affair all along. I kept waiting to hear
them argue that the ethical laxity of the Korean lab only proved that the
moral of judgment of stem cell researchers couldn't be trusted--that no matter
what promises the scientists made to uphold human dignity in their work, they
would surely start committing atrocities once they were allowed to operate
freely. (My hunch is that the clear willingness of so many in the stem cell
community to push for strong codes of scientific ethics has blunted this
attack so far.) Something tells me that those kinds of criticisms will become
much more common shortly.
How does all this affect the international competition for stem cell
dominance? American researchers like Robert Lanza of ACT have been complaining
that the successes of Hwang's lab underscored how the U.S. had squandered its
initial lead in this area of science. Korea might not have had the largest set
of resources thrown against the problem, but Hwang's stardom certainly made it
a frontrunner. If Hwang's work is illusory, though, the center of power would
seem to have swung back over to the U.S.--that is to say, California.
How will Korea respond? Hwang has been a national hero over the past couple of
years. The country had designed a stamp to celebrate stem cell research, for
pete's sake! This may be a crushing blow for many Korean nationals.
Might this scandal end up helping the cause of good stem cell science? Many
scientists and ethicists have been arguing for some time that some
international code of responsible stem cell research needs to be accepted by
the global scientific community. Some of them have further argued that it
behooves the U.S. to spearhead this movement. Perhaps the Hwang affair will
give that issue some traction.
If the Korean lab can't clone embryonic stem cells from adults, can anybody?
How close are we to achieving that goal in reality? How much of a real setback
is it for stem cell science if we can't, given that the application of
embryonic stem cells to therapies was probably some way off anyway?
Who knew what when? That June 17 Science paper has 25 coauthors. It's easy
right now to focus all the attention on Hwang because he was the principal
investigator and rightly did have ultimate responsibility for the project. For
example, Hwang said that some of the enthusiastic female researchers in his
lab had gone behind his back to donate their own eggs even though he had
counseled them not to. Still, as the principal investigator in the lab, he
should have known where all the materials came from, so that's not much of an
excuse. But surely at least some of those other coauthors had to have known
that something fishy was going on if indeed so much of the data was falsified.
If they didn't know, why not? Not to pick on Gerald Schatten, but what exactly
was his role in this research supposed to be and, in retrospect, did he
discharge those responsibilities as well as he should? In short, how many of
the names on that author list are at least as guilty as Hwang seems to be in
having perpetrated and covered up a scientific fraud? (And again, not to make
excuses for him, but is it conceivable that Hwang supervised all those
coworkers so loosely that he didn't know the extent of the fabrication until
And the obvious question: what were Hwang and company thinking? What made them
think that they could fabricate results for a study that would inevitably
receive almost unlimited scholarly attention? How did they think they could
keep the evidence of their fabrication under wraps indefinitely? What were
they going to do when the rest of the scientific world started asking them to
produce more cloned cells under more supervised conditions?
There's an old wry observation that if you look back at disastrously bad
decisions made throughout history, you could probably find someone connected
to each who would have said, "Well, it seemed like a good idea at the time."
But I can't see how anyone in the Hwang lab could have ever even thought that.
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