In the war against the type of cancer called Hodgkin's disease, one major obstacle has been the failure of scientists to grow the tumor cells in culture dishes. About 10 years ago, one scientist suddenly claimed to have successfully produced not one but four lines of Hodgkin's disease cells.
They were said to be the first ones ever grown in a laboratory, and for seven years afterward, the grower of the cell lines, Dr. John C. Long of Harvard University and the Massachusetts General Hospital, studied the characteristics of the cells to seek clues to the nature of Hodgkin's disease. Eventually, he sent samples of his cell cultures to other scientists.
Most of the scientists were suspicious from the moment they saw the cells. But no one was quite sure what was wrong until Dr. Nancy Harris, a researcher in Long's lab, finally took the time to do the experiments that gave the reason why the cells looked so funny:
They were not Hodgkin's disease cellat all; in fact, they were not even human cells, but were owl monkey cells, according to Harris' report in a recent issue of Nature magazine.
Whether the cells accidentally were contaminated with owl monkey cells, or were contaminated on purpose, is now impossible to determine. Eventually, Long was told there was something wrong by a government reseacher. Nonetheless, for at least six months after he knew they were no good, Long still told colleagues they were human hodgkin's cells.
Long's case is one of at least five scientific scandals now being investigated by various parts of the National Institutes of Health or its parent agency, the Department of Health and Human Services. It also is one of at least eight major cases of scientific scandal, most of them involving the faking data, that have been exposed over the past decade. The Food and Drug Administration has uncovered 30 researchers faking data or otherwise misbehaving in the past five years.
In the world of science, where scandals are rare, that seems to some like a crime wave. A few examples:
At Memorial Sloan-Kettering Cancer Institute in 1974 it was found that a researcher had painted mice to make them look spotted -- black spots on white mice and vice versa. The idea was to show that skin grafts from another species of mouse had succeeded.
A psychiatrist was supposed to have tested 12 psychoactive drugs for the FDA over several years. But when an FDA auditor finally visited the laboratory where the tests were supposedly done, he found a single executive chair in the room. The visiting auditor was even more surprised when he was brought a "kindergarten-sized" chair to sit on. During the talk with the FDA man, the psychiatrist repeatedly got up to adjust the thermostat.
Another researcher, caught having faked data for a drug company test, said that he had only done it because his real data had been lost in a rowboat accident at a picnic to which he had unaccountably taken his papers. It turned out later that he had no doctorate, either, but had faked his credentials.
At Boston University, someone faked data on cancer patients' charts to make it appear that they were doing much better than they actually were.
Frudulent work damages more than the public image of science. Since most scientific research is done privately and often without direct checks of veracity, widespread distrust could destroy the whole method by which such work is done.
"We take these things very seriously, more seriously than any of the financial cheating or other things that happen," said Dr. William Raub, NIH official in charge of grant and contract management. He and other scientists have sensed a greater number of scandals being reported in science in the past six or seven years.
"But we have no way of knowing if there is more out there, or simply more is being reported," said Raub. "I think it's probable there has been a more aggressive reporting of scientific fraud by the press. I think that's a good thing, and keeps before us our responsibilities."
At the FDA, Alan Lisook, chief of the clinical investigations branch, said that in the past three years, his agency has considerably increased its staff in an agressive move against scientific fraud.
"We would have hoped to see the cases go down since then," he said, "But the more we look the more we find. It's still continuing at a steady rate; there are more cases pending now than ever before."
The National Institutes of Health, which gives 18,000 grants a year, has funded new work by several of the guilty scientists before finding out about their misdeeds. Now it has begun to set up better ways to deal with the faking of data.
NIH has just adopted a procedure called "debarment," under which researchers found guilty of scientific fraud can be prevented from receiving further federal grant money for research. NIH always has had the power to pull back a grant after fraud is found, and has debarment powers for financial misdealing. But the rules have allowed no punishment for those who fake data, a noncrime many scientists consider worse than misuse or theft of grant money.
Another procedure being started at NIH is to build into the computer system an alert, so that any time the name of a scientist under investigation comes up -- especially in a new application for a grant -- everyone involved will be alerted, according to Raub.
Raub said the alert system was started after a case not long ago in which a midwestern scientist under investigation submitted an application for a new grant. The application got far through the bureaucracy without any direct communication between the two ends of NIH.
The Hodgkin's cells are not the first problem Long has had. In 1979, a young lab assistant caught the scientist faking data in one of his research papers, to avoid doing some tedious but important biochemical experiments.
One question is raised in his case was motivation. In the instance of the faked paper, a hospital press release indicated it was the pressure of competition for grant money that moved him to do it. But Long says he doesn't buy that excuse in his own case or others.
"It's a common excuse," he said. "But I don't buy it. . . . One is under a good deal of pressure to produce, and if you don't produce you don't get the money."
But that is not enough to move one to fraud, he said, otherwise there would be far more of it. The real cause in Long's case, he said, "was the gradual loss of my sense of responsibility as a scientist. Science is built on a sense of trust and 'i violated that. I simply was impatient to get on. . . . So I reported work that I had not done. I was not mindful of my responsibility."
Long had started the Hodgkin's cell lines years before the research paper incident, and learned the cell lines were contaminated months before he was fired for faking the paper. But the bad cell line case was not fully revealed until the recent Nature article.
The article, which says that the Hodgkin's cell lines were not what Long reported them to be, leaves open the question of whether the cell cultures deliberately were contaminated. Accidential contamination of cell cultures is a relatively common event, and experts estimate that 5 percent or so of all cell lines become contaminated over the years.
Nature reported that three of the four cell cultures grown by Long were monkey cells. The fourth was human, but not from a patient with Hodgkin's disease. Also, the chemical signature of the fourth cell line did not match that of the patient from whom it was supposed to have been taken.
But whether the cell lines were faked or accidentally contaminated, Long nonetheless admitted telling colleagues the cell cultures were all right for at least six months after he clearly knew they were defective.
In an interview with The Washington Post, Long fully admitted both the previous falsifying of data that lost him his job, and admitted telling colleagues that the cell cultures were all right when he knew they were not.
"I should have sat down with my colleagues and told them,'Look, we have a problem with the cell lines. We have tostop work and deal with it,'" Long said. "But I didn't do that; I went on as if it was okay."
Long, who now is trying to start a second life by doing routine hospital pathology, says: "I don't think there is any justification for what I did, and I don't offer any excuse. It was wrong."
The Nature article, which tested and proved that four cells lines grown by Long were not Hodgkin's disease cells, was written chiefly by Harris, who lost more than two years of work because of the bad cell lines and Long's failure to halt the work when he found out. The article was intended to warn all those who received the cell cultures from Long, and all those who referred to his work in their own studies, that the Long cultures and the conclusions he drew in several papers from them, might be defective.
Long's work apparently was cited in more than 30 other papers, and the cell lines themselves were sent out to at least seven, an probably more, laboratories.
In medicine, such tumor cell cultures provide isolated malignant cells -- those that are the heart and cause of the cancer -- so they can be studied for clues about how they live and grow, and what agents may stop that growth.
No one before or since Long's supposed Hodgkin's cells has been able to grow a long-lasting culture of Hodgkin's disease cells.
"Then Long, practically out of the blue sky, produced not one but four cell lines. This was a phenomenal achievement," said Dr. Walter Nelson-Rees, a cell-contamination expert.
The cells were used in studies for some years, and the work gave great credence to one particular theory of th e origin of Hodgkin's disease.
Now that theory has had a strut pulled from under it, and researchers are back to a position of the early 1970s, when no convincing Hodgkin's cell lines existed and the origin of the disease was a mystery.