Notebook

LIFE GOES ON: Francis Collins says he won't change his style. In an October 1 "Dear Colleague" letter to 100 or so leukemia genetics researchers, geneticist Francis Collins explained that he was retracting five research papers on leukemia in leading scientific journals because a junior colleague falsified data. News of the letter was originally reported in the Chicago Tribune on October 29 (J. Crewdson, page 1). Collins, director of the Human Genome Project and the National Center for Human Genome Research (NCHGR), part of the National Institutes of Health, told the Tribune that the junior scientist confessed to a "stunning series of data misrepresentations and outright fabrications extending over a period of at least two years." Collins found out about the fabrication in mid-August when a journal editor pointed out that an anonymous reviewer had raised questions about a manuscript he and the colleague, later identified by the New York Times as University of Michigan graduate student Amitov Hajra, had submitted for publication. Hajra had worked in Collins's NCHGR laboratory. Two papers were published in 1995 and 1996 in Proceedings of the National Academy of Sciences, and the others appeared in Genomics; Molecular and Cellular Biology; and Genes, Chromosomes and Cancer. The research in question found that a type of acute leukemia was caused by a genetic alteration in white blood cells. Collins tells The Scientist that he wouldn't change the way he runs his laboratory. "It's not an attractive idea that you would change the way you run your lab to assume that all the data is fabricated until proven otherwise." In retrospect, there's little he would do differently. "It comes down to what kind of fail-safe mechanisms you can put in and their effects on the free-flowing, creative nature and mechanism of science. That's not something to mess with. I've thought about it for the last two months, and I'm not sure that there's anything I would do differently," he says. "I think some people who are looking for evidence that science is not a perfect process will say, 'see, scientists are taking public money and making up data.' People who understand how science works won't be as stunned. I don't think too many people's minds will be changed." Geneticist Stephen Friend observes: "The system ran its course and found the discrepancies and dealt with it appropriately." Friend, director of molecular pharmacology at the Fred Hutchinson Cancer Research Center in Seattle, adds: "It's good that scientists police themselves. It just shows that it can happen to anyone." Within the last month, the hot research field of nitric oxide (NO) physiology has been the object of two major biomedical prizes, one of which has been the focus of some controversy. Most recently, the Worcester Foundation for Biomedical Research in Shrewsbury, Mass., bestowed the Gregory Pincus Medal on two pioneers in the area: Robert F. Furchgott, a Distinguished Professor, Emeritus, at the State University of New York Health Science Center in Brooklyn, and Salvador Moncada, director of the Cruciform Project for Strategic Medical Research at University College in London. The prize recognizes researchers who have made significant contributions to the study of hormones, reproduction, and physiology. A $1,500 award accompanied the medal. On October 23, Furchgott and Moncada discussed their contributions to the discovery of the biological role of NO as part of the Pincus Memorial Lecture, which was held at the foundation. For his Pincus lecture, Furchgott gave a talk on the discovery of endothelium derived relaxing factor. Moncada spoke about the biological implications of the discovery of the l-arginine nitric oxide pathway. Last month, Furchgott was a corecipient along with Ferid Murad, former CEO of Molecular Geriatrics Corp. in Lake Bluff, Ill., of the Albert Lasker Basic Medical Research Award (K.Y. Kreeger, The Scientist, Oct. 28, 1996, page 3). Several prominent scientists, including Nobel laureates Max Perutz and Gertrude Elion, expressed their dissatisfaction-some in letters to the Lasker committee-that Moncada was not included among the Lasker award recipients. One of the most vocal critics is Sir John Vane, a Nobelist from Cambridge University who had been Moncada's mentor and collaborator. "I wanted to draw attention to the unfairness of their decision," says Vane. "I'm sure [the committee] knew of Dr. Moncada's achievements." In an E-mail message to The Scientist, Moncada says he is "too close" to the affair to comment on his colleagues' efforts or on the Lasker committee's decision. But in an interview before the Pincus Award program, Moncada acknowledged that he was not bitter toward the Lasker committee, and Furchgott, commenting publicly for the first time on the dispute, said he thought Moncada should have been a corecipient of the Lasker award (E. Thompson, Worcester Telegram & Gazette, Oct. 24, 1996, page B1). As researchers continue work on sequencing the human genome, the three United States national laboratories working on the project announced last month that they have progressed far enough to join forces as a "virtual human genome institute." The Joint Genome Institute will pool the efforts of the Department of Energy's Lawrence Livermore National Laboratory and Lawrence Berkeley National Laboratory in California, and Los Alamos National Laboratory in New Mexico, which hope to sequence about 40 percent of the total human DNA by 2005. The new institute should be fully operational in January, and DOE will spend $150 million to fund it over the next three years. Officials hope it will result in a more efficient use of resources and expertise. Heading the joint undertaking is Elbert Branscomb, newly appointed chief scientist of the DOE Human Genome Project and former senior scientist in Livermore's biology and biotech program. He explains that the labs individually have been developing the technology to proceed with the project, and that the time to move forward is now. "What has happened recently and has caused dramatic shifts in strategy and organization is the rather sudden coalescence of viewpoints [enabling lab scientists to] now turn aggressively to the sequencing task and no other," Branscomb explains. "In the last year, there has been a [change] in the view of what the target should be; we were not ready to progress to the end game of the first phase of the Human Genome Project. The end game is 'sequence the genome, stupid,' in a political metaphor." CELEBRATION: "Noah", right, joins Canisius College's H. James Birx. In the mid-17th century, a bishop named James Ussher pored over the Old Testament, calculated the ages of its patriarchs and successors, and determined that the Earth was created on Oct. 23, 4004 b.c. Advances in several of the sciences have since debunked the bishop's "discovery," but exactly 6,000 years after the date Ussher claimed marked the world's creation, the Center for Inquiry in Amherst, N.Y., threw a "Birth-of-the- Earth-Day" party in "mock celebration of the historic non- event." About 100 people attended the gathering, which included appearances by actors portraying Charles Darwin and Noah and the cutting of a globe-shaped birthday cake, with one candle for each millennium. In addition, H. James Birx, a professor of anthropology at Canisius College in Buffalo, N.Y., delivered a historical survey on geology and evolutionary thought. Coincidentally, the next day Pope John Paul II announced in a formal statement that "fresh evidence leads to recognition of the theory of evolution as more than just a hypothesis." Birx tells The Scientist: "I think it is very wise of the pope to align Roman Catholicism with the advancement of science. It's a wise position for the almost 1 billion Catholics in the world." Next year Birx will become the first visiting scholar at the center, which is the home of the Council for Secular Humanism, the publisher of Free Inquiry, and of the Committee for the Scientific Investigation of Claims of the Paranormal, the publisher of Skeptical Inquirer. That twice as many African Americans as whites experience high blood pressure is not news. But a recent paper concludes that the reason may be due not to biological differences between races, but to black people's experiences of racial discrimination and unfair treatment (N. Krieger, S. Sidney, American Journal of Public Health, 86:1370-8, 1996). Researchers who studied nearly 4,100 black and white men and women determined that African American professionals who are aware of and challenge racial inequality are at lower risk of hypertension than blue-collar African Americans of both genders who say they have not experienced discrimination and do not denounce unfair treatment. "There has been very little rigorous empirical research that has looked at how racial discrimination might harm health," states lead author Nancy Krieger, an assistant professor in the department of health and social behavior at the Harvard School of Public Health. "It seemed plausible to ask whether the twofold prevalence of hypertension in African Americans as compared to whites in the United States might in part be due to people's experiences of racial discrimination." Among the study's interpretations is that "individuals belonging to groups subjected to discrimination may be at lower risk of elevated blood pressure if they are able to articulate, rather than internalize, their experiences of discrimination." According to Krieger, the policy implications include the need to be aware of the forms of racial inequality-such as in neighborhood conditions, education, and employment-and to examine how to eliminate them. "Right now, most of the advice you'll see in pamphlets concerns diet and exercise, and that's all appropriate," she adds. "But if more research bolsters our study, people [will] have to be conscious of what happens with regard to racial discrimination and their various options of responding to that." JUNK DNA: David Sidransky uses DNA microsatellites to detect cancer. There has to be a better way to spot potential tumor cells, contends David Sidransky, an associate professor of otolaryngology/head and neck surgery and oncology at Johns Hopkins University Oncology Center. Microscopic exams often fail to reveal early cancer cells and cells around tumor margins, whereas molecular analysis does. Yet the latter is time-consuming, costly, and difficult to use routinely, noted Sidransky, speaking to science writers attending the Council for the Advancement of Science Writing's 34th Annual Briefing: New Horizons in Science in Baltimore last month. He and his colleagues have been examining bodily fluids in bladder cancer patients for signs of genetic alterations in small pieces of repeated DNA markers called microsatellites. In some cancers, missing clusters of microsatellites indicate chromosomal deletions, and abnormal ones could indicate a genetic alteration and, perhaps, cancer. Sidransky and his colleagues used this test (L. Mao et al., Science, 271:659-62, 1996) and found cancer in 19 of 20 symptomatic patients who later developed bladder cancer. In follow-up tests, they looked at another 20 patients and identified 18 with cancer. He tells The Scientist that microsatellites "will potentially allow us to do early detection as well as determining the potential for spread by examining bodily fluids in patients at risk for cancers. The potential is that we may be able to detect the tumors ahead of anything available conventionally now." For such tests to see widespread use in the clinic, he says, they must be automated and affordable. "We need to have this to allow us to test breast, prostate, and lung tissue in large amounts. We need to get a panel of markers to allow us to do this. It'll still take at least a year," he predicts. He and his colleagues have begun a multicenter study looking at about 400 bladder cancer patients. He contends that "the ability to use these genetic changes to develop tests for early diagnosis and assessment of tumor burden" may enable physicians and scientists to change the perception of cancer as a fatal disease. "We will remove the tumor before it becomes large enough to become life-threatening."

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