Stem cell scandal shocks South Korea

How one stem-cell researcher and a band of conspirators pulled off the biggest scientific fraud in history.

By Cynthia Fox, Fortune

(Fortune Magazine) -- Last year, Hwang Woo-suk was Korea's scientific Superman. He had three institutes, a stamp created in his honor, and, over the years, $60 million at his disposal. His face was plastered on buses in Seoul. Scientific American named him its researcher of the year.

Then, late in 2005, Hwang's world began to fall apart. The man lionized for being the first to clone human embryonic stem cells was reported to have paid some women for their eggs (which he denies) and obtained others from staff (which he admits).

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HWANG'S WAY
1999
Hwang announces that he has created Korea's first cloned cow. He later clones pigs and a dog, Snuppy.
2004
Hwang publishes a paper in Science claiming he has cloned the world's first human embryonic stem cell.
2006
Hwang is fired. Prosecutors find that he cloned no human stem cells.

The ethical breaches didn't upset the faithful - 80 percent of Koreans still backed him, according to polls; hundreds of women offered him their eggs; and President Roh Moo-hyun urged him to continue his work - but soon even more disturbing questions were being raised.

A South Korean TV station claimed that the reputedly cloned cells it tested weren't clones. Other scientists, in anonymous Web posts, pointed out flaws in research papers that Hwang and his colleagues had published in the prestigious U.S. journal Science. Hwang confessed to having lied about some of his stem-cell lines. But last January an investigation by Seoul National University, where Hwang worked, concluded that not a single human embryonic stem cell had been cloned.

Prosecutors finally swung into action, seizing computers, reading 50,000 e-mails and conducting nearly 1,000 interviews. The results of their efforts were almost as surprising as the news that no cells had been cloned: A conspiracy involving at least 17 people had allegedly gone on for nearly three years, making it, by number of active fabricators, the biggest case of scientific fraud in history.

Hwang was fired and indicted for fraud, violating bioethics laws, accepting $2 million based on falsified research, and allegedly embezzling $856,000 in private and government funds. His two chief partners were also indicted, and three others were charged with embezzlement, destroying evidence and bioethics-law violations.

Hwang has denied the charges, claiming that, due to falsification by others, he thought he had the technology to clone human stem cells when he fabricated evidence himself - a key point, his lawyer contends. All await trial outcomes. (A collaborator, Ahn Curie, was exonerated by prosecutors.)

A need to prove itself

How did such a gargantuan fraud go undetected for so long? In part, the answer is Korea itself. Interviews with co-conspirators, stem-cell scientists and Korea watchers suggest that government, media and business are uncomfortably entwined. The President's science advisor was a Hwang co-author. Hwang's former lawyer headed a government committee investigating him. (Both resigned their posts.) And Korea's ethics laws were made as stem-cell research progressed, not before.

"Policymakers violated almost every existing rule for good governance in research," wrote Herbert Gottweis, a University of Vienna bioethicist. As Seoul National University president Chung Un-chan put it, "Most of us, in the name of national interest, exaggerated Dr. Hwang's stem-cell research to make it a national aspiration."

There's no doubt that Korea, which has suffered 900 invasions in 2,000 years, has a need to prove itself - a need that helped it industrialize quickly but, some say, leads to cutting corners. All of its top business conglomerates have faced scandal. The country's hurry-up mentality, its patriotic fervor and its hierarchical structures made it easier for Hwang to carry out his fraud.

Hwang "was long immunized from criticism," says Stanford University stem-cell pioneer Irving Weissman. Adds one Hwang intimate, who asked not to be identified: "In our culture it would be very difficult to say no to Woo-suk."

But it was the product itself that made this a special case. Computer chips and cars turned Korea into an economic force, but stem cells have the power to combat diseases and save lives. Hwang wasn't just a scientist; one commentator called him a "Jesus figure." His sometimes groundbreaking work cloning cows, pigs and a dog helped create that image, and his good looks and piety fortified it. (He woke at 4 a.m. to pray and traveled with his own wok to save money.)

Says Richard Garr, CEO of U.S. biotech Neuralstem: "There is something special about stem-cell technology. With chip or information technology, there's a feeling that each new discovery is inevitable and incremental, regardless of how important it is. Stem cells are magic, the end thing, the ultimate cure. To repair and replace diseased tissue is a human dream - it promises hope for the hopeless, a kind of immortality of the body and mind."

'The fakery snowballed'

Hwang, who worked on a farm as a child, said he created Korea's first cloned cows because he understood them. He wrote more than 25 cloning papers. His goal: to clone pigs with human genes so their organs wouldn't be rejected by humans. Then he reached for the Holy Grail, the first cloned human embryonic stem cells.

Human embryonic stem cells, first isolated in 1998, are the most potent cells, able to morph into and replicate longer than all others. (Adult stem cells form functioning cells of only their own tissues and replicate fewer times.) Because human embryonic stem cells come from spare embryos obtained through in vitro fertilization, they would be rejected if put in another person, much like organ transplants, which require lifelong immunosuppressive drug regimens.

Scientists are studying ways around the problem. Many have thought the fastest might be cloning, in which the DNA in unfertilized eggs is replaced by donor DNA. The egg magically turns back the clock, and - voilà! - an embryo replica of the DNA donor, full of embryonic stem cells. No rejection, no immunosuppressive drugs.

Hwang says he believed his team created the first cloned human embryonic stem cells early in 2003. But when one of his underlings, Kim Sun-jong, couldn't produce any DNA from the cells, the fraud allegedly began. Instead of starting over, according to the prosecutor's report, Hwang told another researcher to get DNA from two adult cells belonging to their "cloned" person, then send the DNA for testing to a friend of a colleague so it could be passed off as an adult and its cloned stem cell. (It's hard to tell just by looking at DNA.)

Prosecutors say the fakery snowballed: Samples were replaced, labels were switched, and stained-cell photos were doctored. Kim began lying to Hwang, prosecutors claim, secretly passing off normal stem cells for cloned ones. (Kim's lawyer declined comment.) Kim also co-authored six papers on Korea's first noncloned human embryonic stem cells that would all be retracted for similar reasons.

But the fraud remained undetected, and in March 2004 Hwang published a paper in Science reporting that his team had cloned one human embryonic stem-cell line - the first time such a feat had been reported in a top journal. A year later, in a second Science paper, Hwang said he created 11 more lines. The scientific world was stunned. "Gobsmacking," said Victor Nurcombe, a stem-cell scientist in Singapore. "Gigantic advance," said Fred Gage in La Jolla, Calif.

Yet even before the second paper had been submitted to Science, all but two of that paper's fake cloned embryonic stem-cell lines had died. Thinking the two that survived were real clones, Hwang ordered photos doctored and DNA tests amplified to cover up the truth, prosecutors say. Says one researcher on Hwang's team: "Those guys - so crazy." In all, some 70 acts of fabrication were alleged by prosecutors.

History's worst case of scientific fraud has had unanticipated consequences. It shook scientists, especially the many who had sought to collaborate with Hwang. And it prompted Science to consider new rules for reviewing papers.

But far from discrediting the field of stem-cell research, the scandal has juiced up the race for cloning patents and helped make California the vortex of research in the area. Ron Green, advisor to Advanced Cell Technology, a U.S. stem-cell company, says that it has "given people a glimpse of what might be possible." It has also pushed businesses like Advanced Cell Technology to find less controversial alternatives to cloning.

As for Hwang, being on trial hasn't stopped him from putting his lab coat back on. A government-approved foundation has given him $2.6 million to clone pigs with human genes, and he says he hopes to reattempt cloning human stem cells. Not even lies, or the possibility of imprisonment, may keep this self-styled Superman grounded for long - or put the promise of stem cells back in the bottle.

Cynthia Fox's stem-cell book, "Cell of Cells," will be published by W.W. Norton in March.

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