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Stem cell experts assess the impact of hwang fraud on research, public trust

American Association For The Advancement Of Science (AAAS) : 14 July, 2006  (Company News)
Some of the nation
Appearing at the AAAS Annual Meeting, the scientific researchers agreed that stem cell science still holds the allure of extraordinary medical advances in the decades ahead. But ethicists warned of a nation divided by the issue, and said that such divisions is likely to create ongoing controversy and conflict that will impede the research.

“I am very excited about stem cell research,” said Laurie Zoloth, the director of bioethics at Northwestern University’s Center for Genetic Medicine. “I still believe strongly in the good and kind men and women who seem to be working very hard on developing this science. The theory and the promise are extraordinary. But let us be clear: What happened in South Korea is a body blow to ethics and a setback to public trust…a fundamental failure in the realm of theology and moral philosophy.”

The animating idea of the research is that stem cells, which are the earliest building blocks of human development, can be harvested and then programmed to develop into different sorts of cells, blood cells, brain cells, nerve cells. Embryonic stem cells have far more versatility than adult stem cells to be transformed into other types of cells.

Scientists worldwide anticipate that such cells could be used to treat a variety of afflictions, spinal cord injuries, diabetes and certain kinds of cancer, among others. But the research also has provoked passionate opposition, and in August 2001 President George W. Bush cited moral concerns about the destruction of embryos in imposing strict limitations on federal funding for embryonic stem cell research.

Embryonic stem cells can be taken from microscopic embryos that are left over from in vitro fertilization procedures. But a key thrust of research is to bypass that source by developing somatic cell nuclear transfer, also known as therapeutic cloning. In that process, a nucleus is taken from a cel, a skin cell, for example, and injected into a donor egg that has had its nucleus removed. That triggers the egg into thinking it is fertilized; it begins to divide and, when it is a mass of about 100 cells, stem cells are available for harvest.

In papers published in Science, South Korean stem cell researcher Woo Suk Hwang claimed that his team had cloned the first human embryo and created patient-specific stem cells through somatic cell nuclear transfer. But those claims unraveled late last year amid charges that his team had unethically used eggs donated by research staffers and fabricated data in the papers. Reports have suggested that Hwang’s team was able to bring the somatic cell nuclear transfer process to the blastocyst stage, but that the researchers did not succeed in harvesting the stem cells.

Hwang was disgraced, but at the AAAS news briefing Friday, scientists said the scandal would have no more than a temporary effect on research. Scientists must now back up and achieve what Hwang had falsely claimed.

“I personally am optimistic… that it is likely to be workable,” said Lawrence Goldstein, a professor of Cellular and Molecular Medicine at UCSD and investigator with the Howard Hughes Medical Institute.

Beyond that, the researchers said, much compelling work is being done in the field. Leonard Zon, an investigator with the Howard Hughes Medical Institute and also professor of Pediatric Medicine at Children's Hospital Boston of Harvard Medical School, cited research in which embryonic stems cells were transformed into blood stem cells, and then transplanted into a mouse with no immune system. The immune system was then reconstituted.

“This is the first time that somebody has taken an embryonic stem cell and converted it into a self-renewing cell population,” Zon said.

Goldstein cited work being done on Alzheimer’s disease and amyotrophic lateral sclerosis, better known as Lou Gehrig Disease. “What we’re currently trying to do,” Goldstein explained, “is to use embryonic stem cells to make human brain cells, in the lab, in culture dishes, and then introduce known genetic changes that cause Alzheimer’s in people, and then use those to test hypotheses about disease development.”

In many cases, it may be inefficient to use embryonic stem cells to reconstitute whole systems, said Evan Snyder, director of the program in Stem Cells and Regeneration at the Burnham Institute in La Jolla, Ca.

“What we’re finding in a whole series of diseases is that they (embryonic stem cells) will go into the degenerating environment and actually rescue some of the cells that are actually there and in danger, the neurons in the nervous system, for example,” Snyder explained. “One may actually get a bigger bang for your buck out of that strategy, picking a little bit lower-hanging fruit.”

But as long as the scientific advances continue to rely on the destruction of embryos, stem cell research will be controversial, said William Hurlbut, a Stanford University professor and member of the President's Council on Bioethics. “The present conflict over the moral status of human embryos reflects deep divisions in our basic convictions and is unlikely to be resolved through deliberation and debate,” he said.

An alternative to somatic cell nuclear transfer, first proposed by Hurlbut, is called altered nuclear transfer. In that concept, scientists would create genetically altered embryos that are programmed so that they have no possibility of implanting in the uterus. Some ethicists feel that could neutralize the charge that researchers are destroying viable human life.

Altered nuclear transfer “could be in the spirit of social pluralism,” he told reporters, and creates the “possibility for sustaining social consensus.”

That claim drew firm disagreement from Zoloth, the Northwestern ethicist. There might be value, she said, in a “mass apology” by anyone involved in Hwang’s false reports, researchers, reviewers, journalists and others. But she predicted that the U.S. would have to learn to live with a complex moral disagreement, and that science would have to find a way to advance even without broad cultural consensus.

Donald Kennedy, the editor-in-chief of Science, was not on the panel, but he attended the session and took questions from reporters about the journal’s handling of the Hwang papers. An internal review is currently underway at Science, Kennedy said; that report will be given to an independent outside panel for evaluation and recommendations.

Kennedy said he faces a recurring question: In analyzing the peer-review reports of Hwang’s papers, has he seen anything that should’ve raised a red flag earlier? “I have to say, I have not,” he said, “but my colleagues may.”

Goldstein called the Hwang deception “despicable,” but suggested that the element of deceit occurs periodically in human interaction. Ultimately, he said, the system responded properly. “I think that while really very terrible, it nevertheless was a) short-lived, and b) pretty readily identifiable by other scientists looking at the data,” he said. “The general experience is that it is hard to perpetuate a lie for very long in the scientific community because mostly we are born skeptics.”

John D. Gearhart, who led the Johns Hopkins university research team that first identified and isolated pluripotent stem cells, concurred with his colleagues’ measured optimism.
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