Anti-Terror Rules on Toxin Availability May Hinder Research and Global Cooperation, Experts Say

(l-r) David Relman, Nancy Connell and Gigi Kwik Gronvall

Regulations on the use of dangerous biological agents were beefed up in the wake of the 2001 anthrax attacks, but the rules may have hindered some legitimate research collaborations and need to be reviewed, specialists told a 25 June briefing organized by the AAAS Center for Science, Technology and Security Policy.

The U.S. "select agent" program was created initially in the 1990s to control transfer of dangerous agents such as anthrax and botulinum toxin. Legislative measures after 2001 further controlled the possession, use and transfer of the agents, including FBI checks on lab facilities and the personnel who use the agents. A 2004 law also outlawed work on viruses that are close genetic derivatives of the deadly smallpox virus.

While not questioning the need for access controls and safety procedures for the study of dangerous agents, researchers have complained about the red tape involved in establishing high-containment laboratories and obtaining and sharing agents, particularly in the case of collaboration with international partners.

"These labs are necessary if you are going to work on diseases that cause harm," said Gigi Kwik Gronvall, senior associate at the Center for Biosecurity of the University of Pittsburgh Medical Center. But there have been controversies over the operation and location of facilities using select agents, including suspension of research at Texas A & M over safety and reporting lapses and a continuing court battle over the proposed construction of a high-level (BSL-4) containment lab at Boston University. (The four safety levels for biological lab are Biosafety Level 1 through 4. BSL-4 requires the strictest safety procedures, including use of ventilated safety suits by lab workers).

There has been a steady expansion in the number of BSL-3 and BSL-4 labs both in the United States and abroad, Gronvall said. A 2005 survey by the Department of Homeland Security estimated that there were more than 600 BSL-3 labs in the U.S., with more being built each year. There is a 10-fold expansion in BSL-4 lab capacity on the drawing boards. Given the increase in the number of labs and the workers who use them, Gronvall said, it is imperative that there be better standards, training and accident reporting.

Gronvall applauded a bill introduced on 12 June by U.S. Senators Richard Burr (R-N.C.) and Edward Kennedy (D-Mass.) that calls for a comprehensive evaluation of the select agent program by the National Academy of Sciences, including whether the program has hindered research or international collaboration. "Having a look at whether or not [the select agent program] really is interfering with scientific progress is definitely needed," Gronvall said.

Since researchers can now synthesize viruses from scratch and genetically modify other organisms, the bill also calls for inclusion of newly discovered or created organisms on the select agents list. The bill also encourages sharing of information with state officials to improve emergency planning, development of minimum standards for biosafety and biosecurity training, and establishment of a voluntary laboratory incident reporting system.

Dr. David A. Relman, associate professor of microbiology and immunology at Stanford University, said he liked the bill's provision for a broad assessment of how well the select agent program has been working. He said there are agents on the current list of 72 that should be removed. "I would take a bunch off right now," Relman said. He cited Burkholderia mallei, an organism that causes chronic pneumonia and is ubiquitous in soils throughout Southeast Asia. It is difficult to collaborate with colleagues on studies of the bug, he said, because of access restrictions. "You can't work with anybody on it now because it's a select agent," Relman said.

The Senate bill also asks the U.S. attorney general and the secretary of the Department of Health and Human Services to issue guidance on the statutory definition of "variola virus," which causes smallpox. The current language outlaws use of the variola major virus or any derivative that contains more than 85% of the gene sequence of the virus. But the National Science Advisory Board for Biosecurity (NSABB), a panel of experts that includes Relman, has recommended that the language be repealed. He said the language is confusing and unneeded. Scientists say there are viruses that are genetically similar to smallpox virus that are relatively harmless but which can be useful in research.

Relman also said the select agent list needs to be reviewed in light of advances in synthetic genomics. If researchers combine half the genome of the Eastern equine encephalitis virus and half the genome of Venezuelan equine encephalitis (both of them select agents), how is the resulting organism be classified? "What do you call it?" Relman asked. "Is it a select agent? Technically, no."

There has been insufficient attention to such issues, Relman said. "I personally worry that if we become too wed to the letter of the law and to just expanding a list because we think we ought to," he said, "we're going to end up with regulations that aren't doing us any good." The NSABB asked for clarification of what is covered now under the select agent rules, he said, and new standards and practices for screening synthetic genomes.

Relman called for better science and better communication with the national security community on ways to prevent dangerous agents from being misused while at the same time preserving a robust research and public health infrastructure in the United States. "We must not harm this infrastructure," he said. "In fact, it needs to be bolstered."

Nancy Connell, a professor in the division of infectious diseases at University of Medicine and Dentistry of New Jersey, described the lengthy approval process she and her colleagues went through to build a new regional biocontainment laboratory that will focus on both bioterrorism agents and newly emerging diseases. She said the overhead costs for the new BSL-3 laboratory are about 3 to 4 times larger than for a lower containment facility. It will cost about $2 million a year to operate the lab, Connell said, at a time when obtaining outside funding has become increasingly difficult.

Aspects of the federal regulations are burdensome, Connell said, but she expressed more concern about the lack of an "environment of transparency and collaboration among agencies that are actually pulling together a lot of the regulations."

While the new legislation might help address some of the researchers' concerns, the bill is unlikely to move forward this year, given the limited number of legislative days remaining and the need for Congress to devote most of its attention to crucial spending bills.

Meanwhile, Relman emphasized that despite the risks surrounding the work with select agents, there are clear benefits from biotechnology and the tools being used to understand the microbial world. He mentioned a new National Institutes of Health initiative called the Human Microbiome Project. It seeks to map the genomes of all the organisms that set up housekeeping on and in the human body. "We can do things to benefit the world around us in ways we couldn't imagine before," Relman said.

The AAAS Center for Science, Technology and Security Policy, now in its fifth year, serves as a communications portal between the academic community and policy-makers. The Center's mission is to encourage new relationships between scientific experts and policy-makers seeking reliable data on critical security policy issues.

Earl Lane

15 July 2008