Stem Cell Meltdown

Flabbergasting.
           
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.
           
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 principle 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 principle 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 too late?)
           
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.

This is reprinted from Scientific American editor’s blog, from December 15, 2005.