By Rick Weiss
Washington Post Staff Writer
Sunday, January 15, 2006; A19
The allegations arrive almost daily at the Office of Research Integrity, the federal agency with prime responsibility for investigating scientific misconduct. They come by phone, fax and e-mail. A few come in envelopes with no return addresses.
All are about cheating in one way or another.
Last year, 265 allegations came in. And while only a small fraction led to findings of actual misconduct, those mostly unheralded cases are remarkable for their similarity to the much more visible South Korean stem cell scandal, a review of federal records reveals.
Like the Korean case, they involve digital photographs manipulated to deceive, cells or tissues surreptitiously swapped, and eye-glazing data strings subtly rearranged.
Several scientists and ethicists said it is becoming clear that, if anything, Hwang Woo Suk was a rather typical faker. What made the case big was not the scope or creativeness of his lies, but the extremely high profile of the scientific field in which he chose to perpetrate his charade.
Despite all the recent hand-wringing, there may be precious few new lessons to be learned from the Korean debacle, several experts said. Even the journal editors who promised to beef up their screening of submitted manuscripts say privately they doubt there is a practical way to intercept the small proportion of scientists determined to cheat.
In the end, several noted, most research misconduct that comes to light, including Hwang's, does so for the most old-fashioned of reasons: Colleagues or former co-workers turn in the cheaters.
Those who perpetrate fraud in obscure specialties may go longer without getting caught and are unlikely to make news when they are busted, experts said. Those who perform their chicanery in the klieg lights of politically contentious fields can expect a quicker and more dramatic demise.
But unless the research involves real medical treatments -- not the case with embryonic stem cells -- the scientific impact of any single case is likely to be modest, experts said.
That is why many scientists do not buy the now-common reprise that Hwang's fraud has "set back" the field of stem cell research by years.
"Did we, for example, change our research plans or stop doing things because we thought Hwang was successful? The answer is no," said Douglas A. Melton, part of a Harvard team that is awaiting approval to begin embryo cloning experiments like those Hwang had supposedly done. "What happened in Korea hasn't sped up or slowed down our progress."
Notable cases of research misconduct blow through public consciousness with low-level regularity.
Last year, a University of Vermont nutrition researcher who had millions of dollars in federal grants pleaded guilty to faking research on menopause and aging.
In the 1990s, scientists at the Lawrence Berkeley National Laboratory falsely claimed they had discovered two atomic elements. In the 1980s there was John Darsee, the Harvard cardiologist who filled more than 100 journal articles with phony data.
And virtually every scientist today knows of William Summerlin, the brazen Memorial Sloan-Kettering scientist who in the 1970s blackened his white mice with a permanent marker to make it look as if skin transplants from black mice had been successful.
Even Gregor Mendel, the revered Austrian monk, is today widely believed to have cooked his numbers and not just his peas, which he used to derive the principles of modern genetics.
"Misconduct has been around forever," said Chris Pascal, director the Office of Research Integrity (ORI), an arm of the U.S. Department of Health and Human Services.
Although the number of allegations has grown in recent years, no one knows whether the actual prevalence of misconduct has changed much. Less than one-quarter of the allegations ORI receives advance to formal inquiries, and the office makes fewer than a dozen findings of misconduct in a typical year.
Many and perhaps most instances occur under the radar, Pascal and others acknowledge. Among them may be some of the many cases that are reported but go uninvestigated because they fall outside ORI's jurisdiction, which is limited to science supported by public health service funds. (Other offices, including one at the National Science Foundation, cover other realms of federal science but handle far fewer cases than ORI.) Periodic changes in the federal definition of research misconduct -- the current definition encompasses "fabrication, falsification, or plagiarism" -- have also made it difficult to detect trends or determine whether scientists are any more or less dishonest than, say, corporate executives or politicians.
When scientists do engage in misconduct, however, they tend to follow familiar patterns.
· Last October, ORI concluded that Xiaowu Li of the University of California at San Francisco falsified three images in a published paper by using old photos of mouse melanoma cells and saying they were human pancreatic cancer cells.
· Last June, ORI found that Jason W. Lilly of the Boyce Thompson Institute at Cornell University electronically replicated the image of a single genetic assay and then altered the copies so they would appear to be multiple assays.
· In November 2004, ORI found that Ali Sultan of the Harvard School of Public Health plagiarized from another researcher's work and, when he came under suspicion, fabricated portions of an e-mail from his postdoctoral student in an apparent effort to falsely implicate the student.
· In September 2004, ORI determined that Charles N. Rudick of Northwestern University used a photo-altering program to change the appearance of recorded nerve signals.
"You do not need to do something highly sophisticated," said University of Maryland professor Adil E. Shamoo, editor in chief of the journal Accountability in Research. "Don't write something in a lab notebook. Take a cell culture and call it something else. Take the eggs you say you didn't take. If stem cells was not such a high-profile area, this would have gone undetected for years."
Hwang's crimes were similarly ordinary, say the Korean investigators who looked into his case.
Using DNA fingerprinting techniques, they discovered that the 11 stem cell colonies, or lines, that Hwang said he had derived from 11 patients were really just two lines, divided into multiple batches. Digital photographs of the two were manipulated to make it seem as though there were 11.
Additional tests showed that the cells came not from cloned embryos but from conventional embryos, made by standard fertilization of eggs by sperm.
To test the veracity of Hwang's earlier claim that he was the first to grow stem cells from a cloned human embryo, investigators took 23 samples of cells he said came from an embryo cloned from a woman.
The DNA patterns of all 23 should have matched the woman's. Instead, 12 had one DNA pattern, 11 had a different pattern, and neither matched the woman's.
Tests showed that the 11 had been derived from a conventional embryo taken from a nearby fertility clinic. DNA patterns of the other 12 indicated they came from another woman who had donated eggs. But no clone had been created. Instead, in an uncommon biological quirk, one of the woman's eggs had spontaneously produced daughter cells through a process known as parthenogenesis.
To complete the fraud, Hwang's team falsified DNA tracings to suggest that the stem cell DNA patterns were identical to those of the donor's. They simply submitted two identical DNA tracings from the donor, altered one just enough to make it look like a fresh tracing, and said one was hers and one was from the stem cells.
The episode has been a huge embarrassment, agree scientists, journal editors and others. But anyone who thinks it has stymied the controversy-hardened field of stem cell research need look no further than the pages of a recent issue of a free newspaper in Washington to know that is not true. "Which comes first . . . the egg or the cure?" asked an ad seeking women to donate eggs for stem cell research.
It was placed by Advanced Cell Technology of Worcester, Mass., a company that for years has been working to make stem cells from cloned human embryos. Melton's team at Harvard and at least one other in California are also close to entering the race.
Success is uncertain, but one thing is sure: Editors who screen eventual submissions will look for every trick in the book. They will publish the best of them -- and then, knowing the limits of their trade, they will hold their breath.