Damned Heretics

Condemned by the established, but very often right

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Qualified outsiders and maverick insiders are often right about the need to replace received wisdom in science and society, as the history of the Nobel prize shows. This blog exists to back the best of them in their uphill assault on the massively entrenched edifice of resistance to and prejudice against reviewing, let alone revising, ruling ideas. In support of such qualified dissenters and courageous heretics we search for scientific paradigms and other established beliefs which may be maintained only by the power and politics of the status quo, comparing them with academic research and the published experimental and investigative record.

We especially defend and support the funding of honest, accomplished, independent minded and often heroic scientists, inventors and other original thinkers and their right to free speech and publication against the censorship, mudslinging, false arguments, ad hominem propaganda, overwhelming crowd prejudice and internal science politics of the paradigm wars of cancer, AIDS, evolution, global warming, cosmology, particle physics, macroeconomics, health and medicine, diet and nutrition.

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Many people would die rather than think – in fact, they do so. – Bertrand Russell.

Skepticism is dangerous. That’s exactly its function, in my view. It is the business of skepticism to be dangerous. And that’s why there is a great reluctance to teach it in schools. That’s why you don’t find a general fluency in skepticism in the media. On the other hand, how will we negotiate a very perilous future if we don’t have the elementary intellectual tools to ask searching questions of those nominally in charge, especially in a democracy? – Carl Sagan (The Burden of Skepticism, keynote address to CSICOP Annual Conference, Pasadena, April 3/4, 1982).

It is really important to underscore that everything we’re talking about tonight could be utter nonsense. – Brian Greene (NYU panel on Hidden Dimensions June 5 2010, World Science Festival)

I am Albert Einstein, and I heartily approve of this blog, insofar as it seems to believe both in science and the importance of intellectual imagination, uncompromised by out of date emotions such as the impulse toward conventional religious beliefs, national aggression as a part of patriotism, and so on.   As I once remarked, the further the spiritual evolution of mankind advances, the more certain it seems to me that the path to genuine religiosity does not lie through the fear of life, and the fear of death, and blind faith, but through striving after rational knowledge.   Certainly the application of the impulse toward blind faith in science whereby authority is treated as some kind of church is to be deplored.  As I have also said, the only thing ever interfered with my learning was my education. My name as you already perceive without a doubt is George Bernard Shaw, and I certainly approve of this blog, in that its guiding spirit appears to be blasphemous in regard to the High Church doctrines of science, and it flouts the censorship of the powers that be, and as I have famously remarked, all great truths begin as blasphemy, and the first duty of the truthteller is to fight censorship, and while I notice that its seriousness of purpose is often alleviated by a satirical irony which sometimes borders on the facetious, this is all to the good, for as I have also famously remarked, if you wish to be a dissenter, make certain that you frame your ideas in jest, otherwise they will seek to kill you.  My own method was always to take the utmost trouble to find the right thing to say, and then to say it with the utmost levity. (Photo by Alfred Eisenstaedt for Life magazine) One should as a rule respect public opinion in so far as is necessary to avoid starvation and to keep out of prison, but anything that goes beyond this is voluntary submission to an unnecessary tyranny, and is likely to interfere with happiness in all kinds of ways. – Bertrand Russell, Conquest of Happiness (1930) ch. 9

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Stem cell debacle – fraud not quite confirmed, but data bad, and promise clearly exaggerated

Another sorry tale of scientific three card monte is pretty much confirmed today (Dec 17 Sat) as the now notorious Korean researcher, Dr Hwang Woo Suk, has asked Science to discredit his own headline making article in May, which reported his lab breakthrough towards making stem cell therapy a reality. His results were misleading, and athough he hasn’t admitted it, seem to have been duplicitous.

As Gina Kolata wrote yesterday:

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 within sight.

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.

The news has the sad but salutary effect of raising two questions in science that have long been swept under the carpet by the media who act as public relations spokesmen for the leading scientists who feed them news.

1) How come the peer reviewers at Science didn’t detect fraud visible in the very photographs attached to the paper they approved, which Korean graduate students soon exposed on websites?

2) Is the whole fanfare for stem cell therapy overblown, yet another example of exaggerated promise designed to win funding for a line of research which is probably a cul-de-sac, at least in the short run? Examples of such unjustified or overpromoted calls on the public purse that critics can point to include genes that cause cancer, the human genome project, and the new cancer genome project.

At least the normally somnolent New York Times is alert to the dangers in this case, as today’s report by Nicholas Wade, “Cell Researcher’s Retraction Leaves Vexing Questions”, makes clear.

Now that Dr. Hwang Woo Suk has asked Science magazine to withdraw the June 17 article in which he reported what seemed a striking advance toward the goal of treating patients with their own regenerated tissues, scientists have two formidable tasks ahead of them.

The first is to decide how much of the work of Dr. Hwang, of Seoul National University in South Korea, can be relied on. The second is whether scientific journals’ procedures for detecting spurious claims can and should be improved.

… Scientists disagree as to whether Science’s reviewers should have detected the problems with Dr. Hwang’s article. “Should reviewers have caught some of this? Yeah, probably they should have,” said John Gearhart, a stem cell expert at Johns Hopkins University and a member of Science’s board of reviewers. “Obviously great claims require great proof, and maybe more people should review such a paper,” he said.

Dr. Arthur Levine, dean of the University of Pittsburgh medical school, where a committee is investigating the work in the Science article for possible misconduct, said he agreed that Science’s referees “might have been more critical, but that is hindsight.” He added, “Almost six months have elapsed since the paper was published, and it had been widely read by many fine scientists without challenge.”

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The New York Times

December 17, 2005

Cell Researcher’s Retraction Leaves Vexing Questions

By NICHOLAS WADE

Now that Dr. Hwang Woo Suk has asked Science magazine to withdraw the June 17 article in which he reported what seemed a striking advance toward the goal of treating patients with their own regenerated tissues, scientists have two formidable tasks ahead of them.

The first is to decide how much of the work of Dr. Hwang, of Seoul National University in South Korea, can be relied on. The second is whether scientific journals’ procedures for detecting spurious claims can and should be improved.

The editor of Science, Dr. Donald Kennedy of Stanford University, said yesterday that he would allow the paper to be retracted if all the other authors agreed with the request. Dr. Gerald P. Schatten of the University of Pittsburgh, the senior author, asked to withdraw his name from the article on Monday.

Dr. Hwang had conceded that there were problems with some of the data in the article, Dr. Kennedy said, but that “there is certainly no basis right now for a charge of scientific misconduct.”

Dr. Hwang claimed yesterday that he had succeeded in making embryonic cell colonies from some patients, but that the cells were killed by a fungus. His withdrawal of the paper and his acknowledgment of problems with some of its data have inevitably raised doubts about his previous work.

“It is clear now that every experiment published by Hwang will have to be confirmed in some way before being believed,” said Rudolf Jaenisch, a biologist at the Whitehead Institute in Cambridge.

Scientists disagree as to whether Science’s reviewers should have detected the problems with Dr. Hwang’s article. “Should reviewers have caught some of this? Yeah, probably they should have,” said John Gearhart, a stem cell expert at Johns Hopkins University and a member of Science’s board of reviewers. “Obviously great claims require great proof, and maybe more people should review such a paper,” he said.

Dr. Arthur Levine, dean of the University of Pittsburgh medical school, where a committee is investigating the work in the Science article for possible misconduct, said he agreed that Science’s referees “might have been more critical, but that is hindsight.” He added, “Almost six months have elapsed since the paper was published, and it had been widely read by many fine scientists without challenge.”

Unlike readers, a journal’s reviewers can demand more data on points that do not persuade them. But reviewers are unpaid, and their main task is to judge whether the data presented to them support the claim being made. Dr. Kennedy said that the reviewers could not be expected to detect deliberate falsehoods and that he could not see any generic fault in the peer review system.

Dr. Levine said he saw “terribly important lessons” in the Hwang incident, chiefly that the senior author of an article is responsible for its integrity and must therefore be “intimately familiar” with the data. However, the true test of science is replication of a claim by others, Dr. Levine said.

Other scientists have expressed the fear that a replication – the success by a second laboratory in cloning human cells – might have seemed to vindicate Dr. Hwang’s work, if the present criticisms had not come to light. Any Nobel Prize might then have gone to him, not to the scientists who had apparently come second. “If the procedure works indeed and other labs would have repeated it, the credit would have gone to Hwang,” Dr. Jaenisch said.

In the wake of the problems with the June Science article, scientists are now looking more skeptically at some of Dr. Hwang’s other work. In an article published in Science in March 2004, he claimed to have performed the first nuclear transfer with human cells, the cloning procedure in which a nucleus from a person’s adult cell is inserted into a human egg, from which embryonic stem cells are obtained.

An unusual feature of the 2004 paper is that Dr. Hwang inserted a woman’s nucleus into her own cell. Both Dr. Jaenisch and Dr. Gearhart said that Dr. Hwang had offered a reasonable explanation for this self-cloning procedure and should be given the benefit of the doubt.

But Dr. Robert Lanza, a rival cloner at Advanced Cell Technology in Worcester, Mass., said the design would protect Dr. Hwang against critics who asked for the donor and cell to be subjected to a DNA fingerprinting test.

DNA fingerprint tests were indeed demanded by Science’s reviewers for the 11 colonies allegedly derived from patients in the June 2005 paper, and Dr. Hwang provided them.

But critics have said that in some cases the fingerprints Dr. Hwang provided have the identical background noise, as if a single test were being presented twice, instead of two tests having been made independently.

Dr. Lanza also pointed to a similar article by Dr. Hwang in the August 2005 issue of the journal Molecular Reproduction and Development. The identical photograph, a test of pig embryonic cell colonies, seemed to have been presented twice but as representing different cells. The first photo shows embryonic cells said to have been cloned from an adult pig, and the second embryonic cells labeled as from a fertilized pig egg.

Dr. Lanza also expressed doubt about the cloned dog, Snuppy, which Dr. Hwang announced in Nature, Science’s rival publication, in August 2005. Nature’s editors should have required a test of the mitochondrial DNA of Snuppy and the dog it was cloned from, Dr. Lanza said. If a true clone, the mitochondrial DNA of Snuppy and the egg’s donor would be different.

But Dr. Hwang, in a very brief report with little data, reported only that the nuclear DNA of Snuppy and the adult cell donor were identical. This would not rule out the possibility that the two dogs were in fact identical twins obtained by splitting an embryo and delaying the gestation of the second twin. “I think it’s essential that he immediately allow independent testing of the original and cloned animals,” Dr. Lanza said.

Dr. Gearhart agreed, saying, “That would be the very first thing that anyone would have asked.”

Seoul National University is conducting an inquiry into Dr. Hwang’s work, and its committee, with access to Dr. Hwang’s colleagues and data, may be in the best position to decide which, if any, parts of his work are valid.

For the committee members’ findings to have credibility, Dr. Gearhart said, it was “critical they bring in people from outside and who know the field.”

* Copyright 2005The New York Times Company

Gina Kolata’s news analysis yesterday, “Scandal for Cloning Embryos: ‘A Tragic Turn’ for Science”, also noted the backstage problems in science that the case may signal.

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.

….”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.”

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The New York Times

December 16, 2005

News Analysis

Scandal for Cloning Embryos: ‘A Tragic Turn’ for Science

By GINA KOLATA

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 within sight.

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.”

* Copyright 2005The New York Times Company

The whole episode serves to reinforce the skepticism which this site and all too few other media platforms for science critics purvey about AIDS and other paradigms which the critics say resemble fund raising science bubbles than legitimate avenues of mainstream research spending, at least at the exaggerated levels that they attain with overblown promises.

Tom Bethell’s new book, “The Politically Incorrect Guide to Science (Regnery)”, scores a bullseye on this topic with his chapter on “The Stem Cell Challenge to Bioengineering” (p 131).

The seasoned science skeptic Bethell mentions that Gina Kolata’s current caution on scientific breakthroughs including stem cell research follows a dinner party three years ago when “DNA star Jim Watson…told her at a dinner party that Dr. Judah Folkmanm “is going to cure cancer in two years”, a report she wrote up on the front page of the New York Times, to her subsequent embarrassment.

As a result, the Times has put stem cell setbacks on the front page, including the difficulties with the expected cure for Parkinson’s disease (which resulted in the transplanted fetal cells growing all too well, emitting so much dopamine that they “writhed and jerked uncontrollably” with no way to remove them). This is one example of the general danger of embryonic stem cells: they are cancerous.

Other media have been suitably wary, as many of the claims (for example, that adult stem cells could revert to other types of tissue) turned out not to be true.

In other words, the premature promise of stem cells has been well noted before this example of conscious fraud. Hopes are hyped. Real breakthroughs may be decades away.

Bethell quotes Von Baer, a 19th Century resident of Germany and Russia, who said that “all new and important ideas must pass through three stages: first dismissed as nonsense, then rejected as against religion, and finally acknolwledged as true.”

Bethell cracks that stem cells show that today the process is reversed. The new idea is “first hailed as true, then bolstered by religious opposition, and finally acknowledged as false.”

Certainly it is true that there is much in Bethell’s book that makes one wonder if his own skepticism is driven by religion, though nothing explicit. But in this case, at least, he has the followers of Mammon on his side.

The stock market shows what hard headed businessmen and investors think of the current promise of stem cells: not much. Embryonic stem cell drug developer Geron’s stock is $8.74 this week, compared with nearly $70 in March 2000.

The real irony is that Dr Hwang might have been suckered by the very hype that presumably won him support and an easy ride through the obstacle course of peer review. For the only point of committing such fraud, as far as the scientists who comment can explain, is that if you pretend to make a breakthrough and someone else genuinely succeeds soon afterwards, then you get the Nobel, not them.

Here are the main news stories on the topic of Dr Hwang’s three card monte for the past week or so:

Korean Scientist Said to Admit Fabrication in a Cloning Study by Nicholas Wade (Dec 16 Fri)

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The New York Times

December 16, 2005

Korean Scientist Said to Admit Fabrication in a Cloning Study

By NICHOLAS WADE

Correction Appended

(Correction:Because of an editing error, a news analysis yesterday about a colleague’s statement impugning the stem cell research of Dr. Hwang Woo Suk, a South Korean scientist, misstated what Dr. Hwang said about it last month. Dr. Hwang admitted then that an error had been made in submitting photographs that accompanied an article about his research, but he has not publicly admitted that he fabricated evidence, and has defended his research.)

The South Korean scientist who claimed a stunning series of advances in cloning and stem cell research has admitted that critical parts of one discovery were fabricated, a colleague said yesterday.

The colleague, Dr. Roh Sung Il, a co-author of a paper in the journal Science last June in which the scientist, Dr. Hwang Woo Suk, claimed to have created stem cells from 11 patients, told the Korean television station MBC, “Hwang today made statements totally contrary to what we have believed is right. ” Dr. Roh added, “Nine of the 11 stem-cell lines he had said he created didn’t even exist.”

But in a press conference this morning in Seoul, Dr. Hwang defended his work, saying he had proof of his success. He said the patient-tailored stem cells had become badly contaminated but that five frozen stem cells were being thawed for analysis.

Barbara Rice, a spokeswoman for Science, said the journal had asked all of the co-authors of the disputed paper “to clarify these unconfirmed rumors that we are getting.” Dr. Hwang, at his news conference, said he had asked Science to withdraw the article as a result of the uproar.

Over the past two years, Dr. Hwang, a veterinary medical researcher who turned 53 yesterday, became a hero in South Korea and an international celebrity.

Last year he claimed to be the first to clone a human cell, inserting an adult cell’s nucleus into a human egg to make embryonic cells. This year he said he had done the same thing in 11 patients, the first step to the dream of treating people with their own regenerated tissues. And for good measure he said he had cloned a dog as well, a feat that has long frustrated other clone researchers.

This morning, Seoul National University Hospital said Dr. Hwang had been hospitalize there for a week for treatment for stress and was released today. Later, when asked at the press conference why Dr. Roh would have said he had faked some of his work, Dr. Hwang said that Dr. Roh had visited him at the hospital yesterday and raised concerns about the research. Dr. Hwang said he had agreed that some of the work needed to be verified, and that he expected to accomplish that in 10 days. But he said: “We retain our original core technology. We found out later that our management had been poor and as the head of research I feel a grave responsibility.”

The first hints of trouble with Dr. Hwang’s research came earlier this year, when reports emerged that women who worked in his laboratory may have donated eggs for an experiment in cultivating stem cells from a cloned human embryo. Last month, an American collaborator, Dr. Gerald Schatten of the University of Pittsburgh, severed ties with his group, citing “ethical violations” over the way the eggs were obtained.

All these achievements, and his earlier work as well, are now under suspicion.

Dr. Hwang’s new troubles were presaged earlier this week when Dr. Schatten, the senior co-author of the Science article, wrote to the journal asking that his name be withdrawn from the article and urging Dr. Hwang and the other co-authors to retract it. Dr. Schatten wrote that he had “substantial doubts about the paper’s accuracy” and had heard that some of the experiments had been fabricated.

Although the new disclosures are being presented as a blow to Korean science, they can also be seen as a triumph for a cadre of well-trained young Koreans for whom it became almost a pastime to turn up one flaw after another in his work. All or almost all the criticisms that eventually brought him down were first posted on Web sites used by young Korean scientists, although vigorous reporting by MBC television and the online newspaper Pressian also played a leading role.

The young scientists were more skeptical of Dr. Hwang than was Dr. Schatten, who agreed to be senior co-author on Dr. Hwang’s article this June in Science, even though all the experiments had been done in Seoul. The referees and editors at Science accepted the Schatten-Hwang article without spotting the problems that later came to light, although they did ask for extra tests that may have contributed to the denouement.

The debacle is particularly surprising to the many American scientists who visited Dr. Hwang’s lab at the Seoul National University and were impressed by the dedication of his 65 colleagues, the specialization of his lab into separate units for each aspect of cloning, and the technical skill of those who worked the micromanipulators used to suck the nucleus out of human cells.

The event that led to Dr. Hwang’s downfall, after a month of sniping at certain puzzling aspects of his published work, was the posting of a pair of duplicate photos on two Korean Web sites.

One of the new duplicate photos appears in the June Science article about the 11 patients and a second in the Oct. 19 issue of a lesser-known journal, The Biology of Reproduction, where it was reported as being of a different kind of cell.

In the Science article, the cell colony was labeled as being the fifth of Dr. Hwang’s human embryonic cell lines derived from a patient’s cells, but in the Biology of Reproduction article it was designated as an ordinary embryonic cell line generated in the MizMedi hospital in Korea, presumably from surplus embryos created in a fertility clinic.

Critics cited the duplication as confirming suspicions that Dr. Hwang had never successfully cloned any adult human cell and that his Science photos might instead show just human embryonic cell lines derived in the usual way from fertility clinic embryos.

Dr. Roh’s statements make that now seem exactly what happened.

Dr. Roh, the superintendent of MizMedi, was asked by The New York Times on Wednesday to say which type of cell was represented in the photos. Dr. Roh was the senior author of the article in Biology of Reproduction, which Dr. Hwang did not sign. Dr. Roh replied by e-mail that the photo had come from a large computer file of stem cell colonies and that a colleague had accidentally chosen one of the patient-derived colonies to illustrate the Biology of Reproduction article.

Dr. Roh had heard about the error just two hours earlier, he wrote in his e-mail message, and had already written to the editor of the journal requesting that the article be withdrawn immediately. “I really apologize again to have made a big mistake as a principal investigator,” he wrote.

He did not reply to an e-mail message seeking his comment on critics’ demonstration of how the 11 photos in the Science article could have been generated from just two cell colonies. But yesterday he told the Korean news media that Dr. Hwang had confessed to him that the Science photos in fact showed Dr. Roh’s fertility clinic cells, and not cells derived by Dr. Hwang from the adult cells of patients.

In an interview this week on MBC, Dr. Kim Sun Jong, a junior colleague of Dr. Hwang, said his boss had instructed him to take two photos of Dr. Roh’s clinic-derived stem cells and present them as evidence in the Science paper that 11 cell colonies had been successfully derived from patients.

Critics had already begun to screen Dr. Hwang’s previous research for errors. A few days ago they began questioning an article he published in Science last year, in which he announced the first establishment of a human embryonic cell line from an adult cell. The paper in Science this year claimed a greatly improved efficiency in the same technique, and was presented as the first step toward treating patients with their own regenerated tissues.

The criticism of the 2004 paper was that in the published DNA fingerprints of the donor and the cell colony derived from her cells, the trace moves backward a little at certain points. But since the trace is made by a pen moving across a paper strip, the pen cannot usually reverse its movement. The reversals, if real, would point to an abnormality in the machine or to the traces being hand-drawn, in the view of critics. Manual changes would be potential evidence of data manipulation.

John Gearhart, a stem cell specialist at Johns Hopkins University, said the trace was “certainly odd, to say the least.”

Robert Lanza, of Advanced Cell Technology, said, “The traces appear to be hand-drawn.” But another stem cell researcher, Rudolf Jaenisch of the Whitehead Institute, said that, though not an expert in such matters, he could not detect any problem with the traces.

If there was a serious flaw with the 2004 paper, that would apparently mean that no human embryonic stem cell line has yet been created by nuclear transfer, the insertion of an adult cell’s nucleus into a human egg. Dr. Jaenisch said he could not recall any other published paper on the subject besides Dr. Hwang’s. “Right now it is very confusing for all of us and very sad,” said Jose Cibelli, a cloning expert at Michigan State University and a co-author of the 2004 article.

But the fact that no one else has yet replicated Dr. Hwang’s work does not imply it cannot be reproduced, said Dr. George Daley of Harvard University. He has been waiting a year to get the necessary approvals to proceed along the same lines but he could see no technical obstacles to cloning human cells.

Dr. Daley said he had been impressed during a visit to Dr. Hwang’s lab in Seoul at the scale of the operation and the speed and efficacy of the people who worked there. “I have no reason to doubt their technical efficiency,” he said. “If there was any lab capable of doing what they said they did, it would be his lab.”

Dr. Hwang reported in August this year that he had cloned a dog. His brief article in the journal Nature, also with Dr. Schatten, shows two look-alike dogs but offers very little data to prove they are true clones and not identical twins produced by embryo splitting. Dr. Arthur Levine, the dean of the University of Pittsburgh medical school, said that a university committee exploring possible misconduct with the June 2005 Science article would include the Nature dog paper in its inquiry.

Monica Bradford, who as executive editor of Science oversees its selection and publication of research papers, said the situation was distressing for people at the journal, “because this was such a significant result and held so much hope for a lot of people and particularly for Korean science,” and also because “it’s spinning out in the press and no one knows the truth.”

But she said even if the work ended up being retracted, it would not challenge the journal’s review process, in which other experts are asked to assess the strengths and weaknesses of research reports submitted for publication. Though the system has its flaws, “there is no other process that has worked as well,” she said.

Cornelia Dean and James Brooke contributed reporting for this article.

Correction: Dec. 17, 2005, Saturday:

Because of an editing error, a news analysis yesterday about a colleague’s statement impugning the stem cell research of Dr. Hwang Woo Suk, a South Korean scientist, misstated what Dr. Hwang said about it last month. Dr. Hwang admitted then that an error had been made in submitting photographs that accompanied an article about his research, but he has not publicly admitted that he fabricated evidence, and has defended his research. Also because of an editing error, the article misstated the title of Richard Doerflinger, who maintains that stem cell proponents are misleading the public about their accomplishments. He is deputy director for pro-life activities – not “anti-abortion activities” – at the U.S. Conference of Catholic Bishops.

* Copyright 2005The New York Times Company

American Co-Author Wants His Name Off Stem Cell Paper by Nicholas Wade (Dec 14 Wed)

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The New York Times

December 14, 2005

American Co-Author Wants His Name Off Stem Cell Paper

By NICHOLAS WADE

After several days of serious accusations about the validity of a prominent article on the cloning of human cells, the senior author, Gerald Schatten of the University of Pittsburgh, has asked for his name to be removed as co-author, the editors of the journal Science said yesterday.

They also said they were refusing the request because authors could not withdraw their names unilaterally and Dr. Schatten’s Korean co-authors, who did all the experiments, had not yet agreed to retract the article.

The lead Korean author is Hwang Woo Suk, a veterinary researcher at Seoul National University who came to sudden prominence with several striking successes in the cloning field in the last two years. In February 2004 Dr. Hwang reported in Science online that he had established a line of human embryonic stem cells by transferring the nucleus of adult cells to a human egg whose own nucleus had been removed. In June 2005 he said he had done the same procedure with 11 patients, using far fewer human eggs.

The report was hailed as the first step toward the goal of treating people with their own tissues, generated through embryonic cells.

For reasons that are unclear, Dr. Hwang invited Dr. Schatten to be the senior co-author of the article, and he accepted. But last month Dr. Schatten severed his collaboration with Dr. Hwang over the way human eggs were procured for the experiment and placed a correction in Science saying that his only role in the paper had been to analyze data and prepare the paper for publication.

Meanwhile, the paper has come under increasing criticism from Korean scientists. Their accusations, posted anonymously on Korean Web sites, first showed that some of the photographs of the 11 cell colonies were duplicates. Science acknowledged that the accusation was correct but said the duplication occurred when originals were replaced with photographs of higher resolution.

The critics then showed that several of the photographs overlapped, even though they were supposed to be of different cell colonies. Indeed, they said it seemed that as few as two cell colonies had been used to generate photographs.

The critics also noticed a strange feature in the DNA fingerprints taken of the cell colonies and the donors from whom they were supposedly derived. In several cases the pairs of fingerprints seemed to be identical, lacking any of the subtle differences expected in two independent tests.

If this were true, critics say, the paper would not have any evidence that the cell colonies came from the donors or that Dr. Hwang ever performed any successful nuclear transfer experiments.

Eight leaders in cloning technology, including Dr. Ian Wilmut of Edinburgh University, John Gearhart of Johns Hopkins and Dr. Robert Lanza of Advanced Cell Technology, have written to Science saying that they encouraged Dr. Hwang “to cooperate with us to perform an independent test of his cell lines” to see if they matched the donors.

Dr. Schatten’s confidence in Dr. Hwang’s results has also been shaken. In his letter to Science, released yesterday by the University of Pittsburgh, he said he wished to retract his co-authorship of the June 17 article because “my careful re-evaluations of published figures and tables, along with new problematic information, now casts substantial doubts about the paper’s accuracy.”

He also said that over the weekend he had “received allegations from someone involved with the experiments that certain elements of the report may be fabricated.”

The individual was not named, and Dr. Schatten was unavailable for comment yesterday, but Korean press accounts have quoted Kim Sun Jong, a member of Dr. Hwang’s laboratory who now works at the University of Pittsburgh, as saying in an interview with MBC-TV in South Korea on the program “PD Diary” that he was told by Dr. Hwang to make 11 or so cell lines out of the two or three he had in his possession.

The promise of Dr. Hwang’s Science paper is that it seemed to make the long-sought goal of therapeutic cloning quite practical by using only 10 or so human eggs per patient, compared with the 242 used in his 2004 experiment. If the article should turn out to have been fabricated, it would “give a black eye to science in general,” Dr. Gearhart said.

* Copyright 2005The New York Times Company

New Criticism Rages Over South Korean Cell Research

By Nicholas Wade (Dec 10 Sat)

(show)

The New York Times

December 10, 2005

New Criticism Rages Over South Korean Cell Research

By NICHOLAS WADE

A new round of criticism has broken out in South Korea over the accuracy of a recent article that reported a striking advance in human stem cell research.

In the June 17 article, Hwang Woo Suk, a veterinary researcher at Seoul National University, reported that he had developed embryonic stem cell colonies from 11 patients. The article, published in the journal Science, was hailed as a major step toward the goal of treating patients suffering from many serious diseases with their own, regenerated tissues.

But Dr. Hwang’s research, though praised by the South Korean government, faces mounting criticism from some Korean scientists. The newest questions about the paper concern DNA fingerprint tests carried out to prove that the embryonic stem cell colonies were indeed derived from the patient in question. The test, demanded by referees for Science, was necessary because cell colonies often get mixed up or overgrown by other cells in even the best laboratories.

Usually any two DNA fingerprint traces will have peaks of different heights and alignment and different background noise. But in several cases the pairs of traces in the Science article seem identical in all three properties, suggesting that they are the same trace and not, as represented, two independent ones.

If so, there could have been yet another innocent mixing up of data, as seems to have been the case with duplicate photos – an error that came to light earlier this week. But it is also possible that the cell colonies never existed and that a single DNA fingerprint from a patient was falsely represented as two traces, one from the patient and one from the embryonic cell line allegedly derived from him.

Monica Bradford, the deputy editor of Science, said that the journal had asked Dr. Hwang for an explanation and that experts probably needed to examine the original data in Dr. Hwang’s possession before any conclusions could be drawn.

The new charges have also attracted attention in South Korea. Thirty faculty members at Seoul National University wrote Dec. 7 to the university president, Chung Un Chan, saying that, as experts in the life sciences, “we find a significant part of the DNA fingerprinting data is inexplicable.”

They asked Dr. Chung to create a committee to investigate possible misconduct and added, “We are extremely worried that, by keeping silent, we are endangering the international credibility of the Korean scientific community, which in turn will cause irreversible damage to our country.”

The University of Pittsburgh, where Dr. Hwang’s American co-author, Gerald Schatten, is based, has asked its office that investigates research misconduct to look into this and other problems with the Science article.

Earlier this week the critics noted that several photographs, issued online by Science as a supplement to the June 17 article, were duplicates of one another, though they ostensibly showed 11 different cell colonies. But the duplication appeared to have an innocent explanation. The editors of Science announced that the originally submitted manuscript had 11 different photos and that the duplicates were submitted later, presumably by accident, after a request for higher-resolution copies.

Dr. Hwang did not respond to an e-mail inquiry sent yesterday. He has been hospitalized with an ulcer, said Lorenz Studer, a stem cell specialist at the Sloan-Kettering Institute in New York.

Dr. Studer, who has visited the lab several times, said Dr. Hwang had a large operation with 65 people working around the clock, many of them specializing in minute points of detail in the cloning process, and had made evident progress on cloning human cells. Noting the attacks on Dr. Hwang’s work by other Korean scientists, Dr. Studer said, “It is really difficult for us to judge if there is a problem or someone who has an agenda.”

Dr. Studer is studying two of Dr. Hwang’s human cell lines in his laboratory but said he had not tested them and had no way of knowing if they were derived from the cloning of patient’s cells or from embryos from a fertility clinic.

Though the experiments reported in the Science article were done in Seoul, the person formally most responsible for the data is Dr. Schatten, whose name appears last on the Science article, the position reserved for the senior author. Dr. Schatten recently stated that his involvement was limited to analyzing data and preparing the manuscript. Such services do not usually merit senior co-authorship, raising the question of why Dr. Hwang offered it and why Dr. Schatten accepted.

Dr. Arthur Levine, the dean of the University of Pittsburgh medical school, said that Dr. Schatten was a scientist of stature and had contributed ideas to Dr. Hwang, but that “discussion doesn’t ordinarily eventuate in senior authorship.” He added that he knew for certain that Dr. Schatten “must be deeply regretting” having accepted the co-authorship.

Dr. Schatten was not available for comment yesterday, a university spokeswoman said.

The new critique was first raised Dec. 7 by an anonymous posting on a Korean-language Web site, the Biological Research Information Center. The writer commented on the improbability of two independent DNA fingerprints’ being so similar and concluded, “I cannot help but to say that there were no stem cells from the very beginning because the nearly identical fingerprinting patterns raises strongly the possibility of serious misconduct in experiments.”

The letter and its translation were provided by a Korean scientist at an American university who asked not to be identified because of the possibility of recrimination from the South Korean government.

Dr. Hwang has published three significant cloning advances since 2004, including the first cloning of a human embryo, and is somewhat of a national hero in South Korea. The current furor over his work arose last month when PD-Notebook, an investigative program on MBC-TV, a South Korean network, obtained human stem cell samples from Dr. Hwang and had them tested by an independent laboratory.

The results apparently did not match Dr. Hwang’s, and he then refused to cooperate further with the program. The 30 young scientists who signed the letter to the president of the Seoul National University asked him to follow the University of Pittsburgh’s example and set up a committee to inquire into possible misconduct. Dr. Levine agreed that Pittsburgh’s committee may not be able to get very far, given that all the data is in Seoul, and that it could be logical for the two universities to work together.

If misconduct in any part of the Science paper were established, it could well cast doubt over all of Dr. Hwang’s work. But his evident expertise and his generosity in helping other researchers have deeply impressed American visitors like Dr. Studer and Dr. Schatten. So the possibility that the issues raised by his critics are due to careless handling of data, in a scientific paper that has received far more careful public scrutiny than is usual, cannot be ruled out.

* Copyright 2005The New York Times Company

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