Under a Microscope:
High-Profile Cases Bring New Scrutiny to Science's Superstars
ELISABETH ROSENTHAL / New York Times 24dec2005
In recent weeks, two widely respected scientists have themselves become objects of harsh scientific scrutiny, one accused of serious research fraud and the other criticized for ethical lapses in treating a patient.
By not demanding
answers to that question, we end up with a long life of lies, disease and
grief, being monitored on closed-circuit TV, as if we are all
Dr. Hwang Woo Suk, who stunned the world with groundbreaking cloning research in the past year, was found yesterday by an investigating panel at Seoul National University to have intentionally falsified data in a landmark paper on cloning that appeared in the journal Science this summer.
Dr. Jean-Michel Dubernard, the French plastic surgeon who has pushed the boundaries of transplant surgery, first with hand transplants and more recently with a partial face transplant, is now accused by many other surgeons of rushing to perform an operation that was not well tested and unacceptably risky for his patient.
Though their work is entirely unrelated, the two are part of a new high-profile school of science, where discoveries are often trumpeted at news conferences, sometimes even before they are thoroughly scrutinized by scientific peers or published in scientific journals.
Far from the stereotype of cloistered academics, both Dr. Hwang and Dr. Dubernard are flamboyant showmen, never afraid of the limelight. Dr. Dubernard is a member of France's Parliament. Dr. Hwang, founder of the World Stem Cell Hub, theatrically appeared onstage this summer with a cuddly Afghan puppy, which he claimed was the first cloned dog, Snuppy.
While such high-profile tactics have helped bring science center stage, many critics are complaining that they fundamentally distort the slow, boring scientific method that for centuries has insured the quality of research. In a world where top scientists are increasingly celebrities and millionaires, they said, the limelight can corrupt judgment.
"In these two cases I would say scientists were overzealous, too quick to push ahead," said Dr. Adil Shamoo, editor of the journal Accountability in Research and an ethicist at the University of Maryland. "Scientists feel the pressure of our society like everyone else. Their decisions are clouded by visions of fame and dollars."
Dr. Donald Kennedy, editor of Science — which is in the process of retracting Dr. Hwang's paper — said scientists had become far less collegial in the past decade, pushing hard to be first in their field. "There are enormous pressures to be extremely productive and at the top of the heap," he said.
Fame, scientific prizes and, often, lucrative patents await those who finish first, Dr. Kennedy said, but there is little acclaim for those finishing fifth or sixth. "Scientists want to be recognized like everyone else," he said.
Of course, there are still many scientists who hew to the more conventional model, some of whom are preparing face transplants and doing stem cell research of their own. But, these days they may be at a disadvantage, experts say, adhering to a time-consuming research routine.
"I wanted to proceed according to a scientific approach, and we have been extremely cautious," said Dr. Peter Butler of London's Royal Free Hospital, who has been preparing for the last decade to perform Britain's first full face transplant, which has recently been approved by his own hospital, but still requires approvals from national ethics committees.
He performed and published extensive academic research on a number of related topics, from which injuries could best be remedied by transplant, to the impact of having a new face on a patient's identity.
"We've avoided a race because it is inappropriate and it may make you make some bad decisions," he said. "The damage is not just to the patient but the reputation of the whole field." While Dr. Dubernard's team went through required ethical reviews in France, these are less extensive than in England, experts said.
Dr. Butler said that he would not have performed surgery on the French patient. But he does not regret that Dr. Dubernard took the plunge. "I applaud them in the sense that at some point someone had to move ahead and just do it," he said, noting that a number of surgeons who were dead-set against the very idea of a face transplant had been won over by how well the French patient has done.
In stem cell research, one of the biggest competitors to Dr. Hwang's Korean Stem Cell Hub is the U.K. Stem Cell Bank, a two-year-old government lab near London. Unlike the Korean venture, whose opening this fall was trumpeted with press releases around the world, the British bank is rarely in the news.
With elaborate scientific and ethical guidelines for how its stem cells can be created and used, the British Bank often appears to be moving in slow motion compared to its Korean counterpart, which is in perpetual fast forward. Dr. Glyn Stacey, the British bank's director, declined to be interviewed about the scandal at the Korean lab. "He does not think it's appropriate in the media," a spokesman explained.
In the meantime, Dr. Hwang had been continuously debating the merits of his work in public: calling news conferences, conducting TV interviews and releasing statements defending his research — a strategy that clearly made the editors of Science uneasy.
"It would have been helpful if the authors spent as much time communicating with us as they have holding dueling press conferences," said Monica Bradford, the magazine's executive editor, referring to the fact that both Dr. Hwang and his main Korean rival had gone to the news media.
In answering critics, Dr. Dubernard said he worked fast because there were desperately ill patients waiting for help, and it would be immoral to abandon them. The plastic surgeon said that when he first laid eyes upon the severely disfigured face of the woman who received the facial transplant — she had been mauled by a dog — he could not deny her the operation.
But experts say it is often difficult to disentangle a scientist's motives, since discovery is often accompanied by celebrity and financial gain.
"People use press coverage as a way to judge the value of research," Dr. Bradford said. "They want to know did it get in the papers — not whether it really expands our knowledge."
In Dr. Dubernard's case, the charges are not the quality of scientific work. They are that he unwisely short-circuited what should have been a more thorough evaluation, in order to operate on the mauling victim. He took a leap, when science should proceed in a step-wise fashion.
Some surgeons say the first face transplant should involve only skin, and so mauling victims would not qualify. Such transplants would be simpler, merely providing a new covering for the face, and not depend on getting transplanted muscles to function so that a patient could chew or talk, for example.
Dr. Butler's first patient will be a burn victim who needs only skin, who has already undergone "60 or 70" attempts to remake a face without decent results.
Such people are ideal candidates for this radical and risky surgery because they have learned to "adjust to changing appearances," Dr. Butler said.
source: http://www.nytimes.com/2005/12/24/science/24research.html?adxnnl=1&adxnnlx=1135400615-bOwsKzVchTBp4hINyROyCg&pagewanted=print 23dec2005
Cloning Star Who Fooled the World
ROGER HIGHFIELD / The Telegraph (UK) 24dec2005
The decline and fall of the world's most successful cloner has been a protracted affair. First there were grumbles about how he got hold of fresh human eggs last year after he stunned the scientific community with the first human clone.
A few weeks ago the egg affair degenerated into a scientific soap opera then concerns about his science surfaced. Yesterday the saga ended with his resignation and disgrace.
The world was stunned when a cloned human embryo was unveiled by Prof Hwang Woo-suk. Before his work was published in 2004, claims to have created a human clone had been made. This time, however, details of how to do it were published in Science, one of the subject's most respected journals.
They were reported by a reputable team at Seoul National University, and the human clones were much more advanced than earlier attempts.
But there were qualms. The Koreans had managed to obtain 242 eggs, free, from volunteer donors. This raised eyebrows among American rivals, who would have had to pay thousands of dollars. But Hwang, 53, denied that women in his team donated their own eggs. And he stressed to this newspaper and others that his colleagues had followed guidelines.
Any lingering doubts seemed to be swept away a year later, when the team refined its methods and showed for the first time that cloning could be clinically relevant. In a paper published in Science, and unveiled in London at the Royal Institution, Hwang described how 18 women donated 185 eggs that, with cells from donors, were used to clone embryos and then create lines of embryonic stem cells, each of which could be used to make any of the 200 cell types in the donor patient, with no risk of rejection.
The cells to reprogramme the 185 eggs had been obtained from 11 male and female donors ranging in age from two to 56, including patients who had juvenile diabetes, spinal cord injury and a genetic immune deficiency.
This time there were no quibbles about consent. The Dolly cloning method was used to create 31 embryos which were used to create 11 lines of human embryonic stem cells, with remarkable efficiency. The team also provided evidence that the cell lines matched the patients' cells.
Success depended on many factors, said Prof Gerald Schatten, of the University of Pittsburgh, Hwang's American co-author of the work: the Koreans seemed more adept at microscopic surgery on eggs and embryos; and the eggs were from young donors, high quality, and handled gently.
Last month, the collaboration between Hwang and Prof Schatten was over. Prof Schatten issued a statement that cited "misrepresentations" about egg collection "and the resultant breach of trust". A South Korean television station had also been investigating wider allegations that had also appeared on a website.
In a press conference in Seoul, Hwang admitted that two female scientists in his laboratory had given their own eggs for research. He apologised profusely, confessing that he had lied when the claim was first made in Nature and resigned as the head of a new venture, the World Stem Cell Hub.
Hwang retreated to a remote Buddhist temple, then was admitted to hospital suffering from exhaustion. But when he returned to his lab on Dec 13 the scandal was far from over.
Prof Schatten had by then asked Science to take his name off the May 2005 paper they had unveiled together in the Royal Institution. "My careful re-evaluations of published figures and tables, along with new problematic information, now cast substantial doubts [on] the paper's accuracy," Prof Schatten said. "Over the weekend, I received allegations from someone involved with the experiments that certain elements of the report may be fabricated."
One question was whether photographs, described in the paper as showing stem cells derived from cloned human embryos, were frauds. A co-author, Roh Sung Il of the MizMedi Hospital, said that they were not derived from cloning experiments. He told journalists that a scientist working for Hwang was pressured into creating the fakes. Another question concerned the veracity of the DNA fingerprints used to show that a stem cell was genetically identical to a person who provided cells for cloning.
Hwang and Prof Schatten subsequently retracted the 2005 paper. However, in a televised news conference, Hwang still maintained that the data were essentially correct. Prof Ian Wilmut, of Edinburgh University, who planned to collaborate with Hwang, was among those who signed a letter to Science, asking him to submit his work for independent confirmation.
Even then, Prof Wilmut was convinced that Hwang's team did succeed in obtaining 11 new stem cell lines from cloned embryos. He himself had to do follow up work to convince high profile sceptics in America that Dolly was a clone of an adult cell.
But then it emerged that in January of this year Hwang had reported to his government sponsors that six of his stem lines had been lost to contamination, an important fact not mentioned in his report later published in Science. A few days ago, Hwang said once again that he was in no doubt that he could repeat the success of his techniques.
Yesterday, Hwang's reputation was in tatters. An investigation led by Roe Jung-hye, Seoul National University's Dean of Research Affairs, found that data for the 11 collections of stem cells Hwang claimed to have made were derived from just two stem cell lines.
"Based on these facts, the data in the 2005 Science paper cannot be some error from a simple mistake, but can only be seen as a deliberate fabrication," the panel said.
It will now also investigate Hwang's other landmark papers - including a 2004 article on the world's first cloned human embryos, and an August 2005 paper on the first cloned dog, an Afghan hound.
source: http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2005/12/24/woosuk124.xml&sSheet=/news/2005/12/24/ixnewstop.html 23dec2005
Stem Cell Fraud Worries U.S. Scientists
RICK WEISS / Washington Post 24dec2005
The unwelcome but indisputable revelation that some of the most exciting biomedical claims of the past few years were the product of scientific fraud settled like a cloud over the American scientific community yesterday.
Stem cell researchers said they were depressed and discouraged to learn that an investigatory panel at Seoul National University had found that most of the precious human embryonic stem cell colonies that its scientists had touted were fakes.
The star scientist at the heart of that deception — Hwang Woo Suk — resigned yesterday from his university post, his meteoric rise to fame coming to a wrenching and ignominious end.
Many researchers said they are worried about the political impact of the debacle in the United States, where the Senate is poised to consider several bills that could boost or restrict stem cell research. Although controversial because it involves the destruction of human embryos, the science has had generally high approval ratings with the public because of all the medical promise the cells are thought to hold.
Yet scientists vowed yesterday to learn from the experience and move ahead with renewed vigor, saying they still see the field as extremely promising.
"Although it hurts, I think we have to say that if there is fraud of any kind . . . it has to be exposed, no matter what the cost. The truth is of more value than anything else," said John Gearhart, a stem cell researcher at Johns Hopkins Medical Institutions in Baltimore.
"We'll have to deal with the cynicism and anything that comes our way politically from the policymakers," Gearhart added. "But people should realize that anything that is wrong with the science is of no value to us either."
The investigation is ongoing at the Seoul university, but a panel there announced late Thursday it had found overwhelming evidence that at least nine of 11 colonies of stem cells described in a high-profile report this spring either never existed or were never proved to be stem cells. The colonies were said to have been derived from embryos that were clones of 11 patients, marking the first alleged proof that it might be practical to create custom-designed stem cells to treat disease.
Embryonic stem cells, which have the potential to become — and perhaps repair — virtually every kind of ailing organ, had been made before, but never from cloned embryos. Scientists suspect that clone-derived cells are less likely to be rejected by a patient's immune system.
With Congress out for the holiday break, there was no immediate reaction from Capitol Hill. But opponents of the research clearly saw the disaster as a political plus, and they said it reveals how little evidence there is for stem cells' value.
"It's all very well to say one scandal shouldn't set back the field, but Hwang's team was the field," said Richard Doerflinger, deputy director of pro-life activities at the U.S. Conference of Catholic Bishops, in an e-mail. "If his results are false, then after seven years of attempts worldwide no one has succeeded in getting even the first step in 'therapeutic cloning' to work on a practical scale. At what point do legislators stop throwing away good money after bad?"
Others took the opposite tack, saying that although fraud can happen anywhere and anytime, it would be less likely to occur in the stem cell arena if that field were not so heavily restricted in this country.
"Probably the strongest research oversight system in the world is at the National Institutes of Health, but they are pretty much on the sidelines" because of restrictions imposed by President Bush in 2001, said Sean Tipton, president-elect of the Coalition for the Advancement of Medical Research, which supports stem cell research. "If you don't allow the best American scientists to do the best — and best overseen — research, you force it overseas and into the private sector, and this is the result."
The research journal Science, which published this year's headline-making paper by Hwang as well as a similarly historic stem cell study by Hwang in 2004, said yesterday that it is continuing in its effort to get a full explanation from all the newer paper's authors — a crucial step toward officially retracting the paper.
The journal said it is also checking the 2004 paper for possible fraud. And the journal Nature said it is doing the same for an August 2005 report in which Hwang claimed to have cloned an adult dog, a major first — if true.
It may not stop there. A scientist who has served as a reviewer for research reports submitted to lesser-known journals said in an interview yesterday he has found evidence suggestive of fraud in at least one other paper submitted by scientists at Seoul National University — a paper on which Hwang was not an author.
"It's clear to me that some of these shenanigans extend beyond Woo Suk," the reviewer said, speaking on the condition of anonymity because reviewers are supposed to remain anonymous.
Scientists, ethicists and others said that it can be almost impossible to detect a well-crafted scientific deception — at least at first — but added that greater safeguards are worth considering in the aftermath of the Korean scandal.
Several scientists have noted, for example, that the Hwang laboratory was a highly compartmentalized one, resembling a factory assembly line more than the hive of communication typical of an American lab. When each scientist is aware of and responsible for just a small part of the project, several said, it is easier for someone to fake or misuse a result without anyone else on the team knowing about it.
Scientists and journal publishers are also reassessing the wisdom of allowing a researcher to append his or her name to a report as a "senior author" without having been an integral participant in the research.
That was the case with Gerald Schatten of the University of Pittsburgh, who was the sole American on the 2005 report. Schatten did not contribute to the science but was listed as senior author and shared in the ensuing fame for serving as an "adviser" to the Koreans. He recently tried to extricate himself from the disaster by asking Science to take his name off the paper.
Science declined, saying that senior authors have a responsibility to know what is going on, and the university has launched an investigation of its own.
source: http://www.washingtonpost.com/wp-dyn/content/article/2005/12/23/AR2005122301518_pf.html 23dec2005