Critics are questioning whether a multi-billion-dollar programme to improve public safeguards against dangerous pathogens is really making the United States safer than it was before.

The criticism surfaced in Washington on 4 October, when members of Congress grilled officials of the Bush administration over the rapid expansion of laboratories that house pathogens such as anthrax and Ebola. The same day, the Government Accountabil-ity Office, an investigative arm of Congress, reported that the government wasn’t keeping tabs on the number of such labs in operation, or coordinating their regulation.

“Are so many labs doing this research that you actually increase the chances of a cata-strophic release of a deadly disease?” asked Bart Stupak (Democrat, Michigan) at the hearing of the House energy and commerce committee. The committee heard testimony from senior officials of the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), the agencies that oversee much of the work.

The hearing came three months after the CDC halted research on potential bioweap-ons agents at Texas A&M University in College Station, when a lab worker there contracted brucellosis (see Nature 448, 105–106; 2007).

Documents uncovered by Associated Press have since identified more than 100 mishaps ranging from bird flu transmitted to a lab worker by a ferret bite, to missing vials of anthrax.

Critics of the expansion claim that the mishaps indict the entire biosafety research programme. “This work cannot be safely per-formed in a university or corporate setting,” says Richard Ebright, a molecular biologist at Rutgers University in Piscataway, New Jersey.

Before the terrorist attacks of 11 September 2001 and the subsequent anthrax releases that killed five people in the United States, only a few studies of dangerous pathogens were done out-side fortress-like government facilities such as the CDC’s laboratories in Atlanta, Georgia, and the Army Medical Research Institute of Infec-tious Diseases in Fort Detrick, Maryland.

But to broaden its knowledge and engage lead-ing scientists, the Bush administration ramped up biosecurity research outside those facilities. In 2001, the National Institute of Allergy and Infectious Diseases — the NIH institute that has led the biosecurity agenda — spent $41 million on such work. Last year, it spent $1.6 billion. And the number of biosafety 4 laboratories study ing deadly pathogens without cures has grown from 5 in 2001 to 15 either in operation or being planned today. Currently, 409 labora-

tories staffed by 14,000 people tinker with the various ‘select agents’ tracked by the CDC.

So far, none of the security lapses is known to have harmed the public, says microbiologist Ronald Atlas, graduate dean at the University of Louisville in Kentucky. But Atlas worries that the government has placed more empha-sis on physical security than on training people to handle pathogens safely. “When you work in a lab, you can become complacent,” he admits, “and that just can’t be allowed today.” But he is against the scaling back of pathogen research.

European biologists have criticized the idea of a ‘two-tier’ research publication system floated by the European Commission.

In a ‘green paper’ published on 11 July, the commission asked whether sensitive biological research should be published twice: a public version without sensitive content and a full-content one for “relevant bio-stakeholders”. But several groups have taken issue with the ideas proposed in the discussion document.

The European Biosafety Association (EBSA), which represents people working in biosafety and associated activities, said that it thought the two-tier approach was “unworkable and contrary to scientific freedom”.

Similarly, the bioindustry body EuropaBio, based in Brussels, Belgium,

said: “Pre-publication review of scientific research and possibly classification of its release raises profound questions for scientific freedom — questions that have been addressed in the nuclear field but not substantially in the life sciences.”

Neither group spelled out how it thinks that information on potentially dangerous pathogens, for instance, should be contained. The EBSA, however, suggests that professional associations should develop guidelines on this matter.

The paper provides no details on how a two-tier publication system might work in practice. John Marks, chief executive of the European Science Foundation, a coalition of European research agencies based in Strasbourg, France, says that the question

of who might operate such a system remains unresolved. “In principle it sounds good,” he says. “But the question is: who is going to be the gatekeeper?”

The still-unexplained anthrax attacks in the United States in 2001, together with publications such as those describing the creation of a particularly virulent version of mousepox1 and the synthesis of an influenza strain containing parts of the 1918 pandemic virus2, has led to the consideration of various approaches to control access to some types of biological information (see Nature 441, 388–389; 2006). The green paper was a part of this process, and together with the comments received on it, could eventually lead to European legislation.

As well as the two-tier system of publication, the green paper suggests that

Europe ponders restrictions on life sciences

Congress grills officials over biosafety boom

“In principle it sounds good, but who is going to be the gatekeeper?”

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Two papers published this week challenge the validity of using the protein Oct4 as a marker for adult stem cells. The protein maintains embryonic stem cells in an undif-ferentiated state, called pluripotency, but the papers question whether it has the same function in adult stem cells.

Oct4 controls gene expression during the early stages of embryo formation, but switches off in somatic cells shortly there-after. It thus seems logical that Oct4 might also control adult stem cells, and more than 60 studies have used Oct4 expression as a marker of these cells.

But now, Rudolf Jaenisch’s lab at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, has used sev-eral approaches to test for Oct4 expression in adult stem cells in mice1. All came up nega-tive. “It’s hard to prove beyond any doubt that something is not expressed or doesn’t have a function,” says author Christopher Lengner, also from the Whitehead Institute. “That’s why we had to use overlapping methods. We beat the thing to death.”

Lengner and his colleagues aren’t alone. Several years ago, Lorenza Lazzari, of the Maggiore Foundation Hospital in Milan, Italy, and her colleagues detected low levels of Oct4 expression in adult stem cells, but their negative controls, which did not con-tain stem cells, yielded the same result.

Lazzari had found it difficult to publish her work, but eventually succeeded earlier this year2. “The dogma of Oct4 as a stem-cell marker was stated by several scientists work-ing on somatic stem cells and it has been very difficult to convince editors,” says Lazzari, who says that she has had several manuscripts

on the topic rejected. Many published papers showing Oct4 expression simply didn’t include a negative control, Lengner says.

Lazzari’s false-positive results could be due to the presence of several Oct4-related genes that do not code for functional pro-tein, says Gesine Kögler of the Heinrich-Heine University in Düsseldorf, Germany. Kögler and her colleagues found that many approaches used to detect Oct4 cannot dis-tinguish between the functional Oct4 gene and its related pseudogenes3. Lengner also says that many papers relied on stem cells that had been maintained as cell cultures for many generations, and may no longer reflect what occurs in live animals.

This doesn’t necessarily mean that adult stem cells are not pluripotent, notes Leendert Looijenga, a pathologist at the Erasmus Med-ical Center in Rotterdam, the Netherlands. It does, however, suggest that they are regulated differently from embryonic ones.

Looijenga and his colleagues have tested more than 3,600 cancer tissue samples, rep-resenting more than 100 cancers. They found that Oct4 was often expressed in gamete-pro-ducing tissue, but not in other types of tissue, supporting the link between pluripotency and the protein. Researchers were driven by the idea that Oct4 ought to be present in adult stem cells and stem-cell-derived cancers, says Looijenga. “It’s a logical idea,” he says, “but logical ideas aren’t always right.” ■

Heidi Ledford1. Lengner, C. J. et al. Cell Stem Cell 1, 403–415 (2007).2. Zangrossi, S. et al. Stem Cells 25, 1675–1680 (2007).3. Liedtke, S., Enczmann, J., Waclawczyk, S., Wernet, P. &

Kögler, G. Cell Stem Cell 1, 364–366 (2007).4. Looijenga, L. H. J. et al. Cancer Res 63, 2244–2250

(2003).

Doubts raised over stem-cell marker

“We need more infectious-disease research, not less,” he says.

Despite reservations expressed at the hear-ing, the expansion of bioterror-related research continues. Congress might still use its control of budgets to push for greater oversight, though, and Stupak and others have asked the govern-ment to assess the overall programme. ■ Ewen Callaway

research grants should be awarded, in part, on the basis of applicants’ compliance with biosafety standards. It also puts forward a Europe-wide system for the accreditation of research facilities suitable for work on potentially dangerous pathogens. And it asks whether it would be feasible to accredit individual researchers.

In their responses, the EBSA and EuropaBio backed the accreditation of facilities but said that it would be much more difficult to accredit individual researchers without running into problems regarding discrimination or personal privacy. Both groups broadly welcomed the idea of making grants conditional on compliance with biosafety standards. ■Daniel Cressey

1. Jackson, R. J. et al. A. J. Virol. 75, 1205–1210 (2001).2. Tumpey, T. M. et al. Science 310, 77–80 (2005).

Time for change? A stem-cell marker might not be as specific in adult cells as in embryonic ones.

Could investment in biosafety research be leaving the public more at risk?

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