Battle over biodefense

Like a proud father who puts his first-born on display for family and friends, Alan Cross shows off his new infectious-diseases laboratory with flourish. The 7,000-square-foot lab is equipped with highly sensitive alarm systems, special ventilation hoods, decontamination showers, a hacker-proof computer system, and a variety of other trappings that give rich meaning to the phrase “state of the art.”

The $2 million facility at the University of Maryland School of Medicine in Baltimore soon will be home to researchers studying anthrax, tularemia, and other potential bioterrorist pathogens. So, it follows that the lab would be equipped with a little more than run-of-the-mill safety systems.

“The biosafety efforts are extraordinary,” says Cross, an affable, engaging researcher who enjoys discussing his work. A professor of medicine affiliated with the school’s Center for Vaccine Development, Cross was an infectious-diseases scientist for many years with the United States Army before going into academic research.

The design and equipment for the Maryland lab must be approved by federal authorities—a safety precaution that was put into place following the 2001 anthrax attacks, which left five people dead, sent another 17 to the hospital, and forced some 30,000 to take prophylactic antibiotics. The government also mandates strict screening and registration procedures for all personnel with access to dangerous biological agents.

This scrutiny has led to the advanced safety systems that outfit Cross’s new lab: an independent ventilation system in each of the seven workrooms to prevent leakage of airborne microbes; electronic locking systems on every freezer housing test specimens; and monitoring systems that track the number of times that specimens are removed from the freezer—and who removed them.

The health sciences building that houses the laboratory was opened in May 2003, but Cross and his colleagues still are awaiting the official go-ahead from the Centers for Disease Control and Prevention to begin working in the facility. “And after they review all the safety features of the facility, and also check the qualifications of each of the investigators—taking months and months and months—then the next level is the FBI,” Cross says. “The FBI investigates every single person who is on that application.”

Built with a construction grant from the National Institute of Allergy and Infectious Diseases (NIAID for short), the Baltimore lab represents a relatively modest component of an ambitious, heavily funded federal effort intended to build up countermeasures against bioterrorism and biological warfare agents, as well as naturally occurring pathogens.

Despite vocal criticism from some quarters of the scientific community and organized opposition by citizen activist groups, the government is moving ahead with plans to construct at least 11 new high-security infectious-disease laboratory buildings at universities across the country, and to pump out funds for biodefense research involving eight consortia of universities and other institutions.

NIAID’s spending on biodefense now exceeds the support it provides for HIV/AIDS research, which previously was the biggest item in the institute’s budget. (NIAID makes up about half of total National Institutes of Health spending on the disease.)
Government officials and other proponents of the new labs say they are badly needed to deal with incidents such as the anthrax letter episodes. Supporters also argue that the biodefense effort serves to guard against the specter of large-scale bioterrorist or state-sponsored biological warfare attacks against the United States.

Critics, however, contend that the civilian biodefense program—involving NIAID and the CDC, along with the Department of Homeland Security and other federal agencies—amounts to a politically motivated overreaction to a relatively limited threat. In addition, they charge, the rapidly ramped-up biodefense effort is putting significant pressure on federal funding for other areas of biomedical research.

Their complaints aren’t falling on deaf ears. Strong local opposition factored into NIAID’s decision last year not to build an infectious-diseases lab complex at the University of California, Davis. Vocal criticism from community groups and scientists may succeed in delaying, scaling back, or possibly stopping construction of a similar facility planned for Boston University.

Only a major policy change will alter the government’s plans for a significant expansion in the nation’s biodefense research infrastructure. Still, the battle over biodefense is far from over.

Building up, and up

President Bush has singled out bioterrorism as a “real threat” on more than one occasion. “Armed with a single vial of a biological agent … small groups of fanatics, or failing states, could gain the power to threaten great nations, threaten the world peace,” Bush told senior military officials at the National Defense University in Washington, D.C., earlier this year. “We must confront the danger with open eyes and unbending purpose.”

This “unbending purpose” will not be cheap. A study by University of Pittsburgh biosecurity analyst Ari Schuler, published this summer in the journal Biosecurity and Bioterrorism, offered a detailed look at federal biodefense spending. The United States has spent about $14.5 billion on the overall civilian biodefense effort from 2001 to 2004, according to Schuler’s study. The president’s budget request for 2005 is $7.6 billion, 18 times higher than the amount budgeted just four years ago. About $1.7 billion of this is earmarked for biodefense research.

NIAID biodefense research spending jumped from only $53 million in 2001 to an estimated $1.4 billion in 2004, and is budgeted to reach nearly $1.5 billion in 2005. For other civilian agencies, the administration’s budgeted biodefense outlays for 2005 include: Department of Homeland Security, $2.9 billion; CDC, $1.1 billion; Health Resources and Services Administration (particularly hospital preparedness and infrastructure), $504 million; Depart-ment of Agriculture, $381 million; Food and Drug Administration, $246 million; Environmental Protection Agency, $92 million; and National Science Foundation, $32 million. 

NIAID is funding two large National Biocontainment Laboratories at the Boston University Medical Center and the University of Texas Medical Branch in Galveston, with construction grants of about $120 million apiece. Annual operating costs for each of these facilities are expected to be about $70 million.

They’ll each include BL-4 labs with the highest biosafety rating assigned by the Centers for Disease Control and Prevention.
BL-1 labs, such as those used by high school biology students and college undergraduates, are for work with microbes not known to cause disease in healthy adult humans. BL-2 applies to work performed with biological agents of moderate potential hazard, such as measles virus and salmonella. BL-3 labs, such as the new facility at the University of Maryland, include those with such pathogens as anthrax, tularemia, and tuberculosis.

BL-4 laboratories, such as those planned for the Boston and Galveston labs, have been described as “submarines inside a bank vault.” Heat, pressure, chemical, and incineration systems housed in the vault area process all liquid and solid wastes completely to render them sterile or safe. High-efficiency filtration removes any airborne material. Researchers wear positive-pressure suits connected to independent air sources through breathing tubes. To prevent possible exposure through punctures to the suits, glass and most sharp objects are not permitted. Researchers exiting the workspace must go through a multi-stage shower, including a chemical disinfectant cycle, to wipe out any infectious agents.

Along with the two large National Biocontainment Laboratories, nine smaller Regional Biocontainment Laboratories with BL-2 and BL-3 labs are planned at universities around the country, with federal construction grants of between $7 million and $21 million each. In addition, NIAID is supporting the establishment of eight Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases Research, involving consortia of universities and other institutions. The University of Maryland School of Medicine, home to Cross’s lab, is lead institution for one of these centers. Federal grants for these centers total about $350 million over five years.

Aside from such biodefense research initiatives, the Bush administration’s “Project BioShield” involves large-scale government outlays to procure and stockpile vaccines and drugs to cope with anthrax, smallpox and other pathogens, and to set up a national network of sensors for potential bioterror agents.

Bigger programs, bigger risks?

Officials emphasize that all these initiatives are strictly defensive measures. The United States renounced biological weapons during the Nixon administration. But some critics of the biodefense program contend that it might lay the groundwork for reconstituting a bioweapons capability. This is partly because research at the infectious-disease labs could be turned to developing more virulent, genetically engineering, drug- and vaccine-resistant strains of pathogens.

“The intent, or at least the expressed intent, of the U.S. bioweapons agent program is defensive,” says Richard Ebright, a professor of chemistry and chemical biology at Rutgers University in Piscataway, New Jersey. “However, in practice, this is a de facto offensive bioweapons agent program. It has all the characteristics, all the properties. The scale is larger, in terms of dollar volume and also in terms of research personnel, than the Soviet offensive bioweapons program.”

In part, the current response is one that is dictated by political reasons rather than scientific reasons."
Stanley Falkow

Ebright, a laboratory director at the university’s Waksman Institute of Microbiology, is one of the most outspoken critics of the biodefense program. He worries that the biodefense effort will lead to an unnecessary excess of infectious-disease lab space and increase the risk of an intentional or accidental release of a deadly pathogen.

In addition to the new BL-4 facilities at the new National Biocontainment Laboratories in Boston and Galveston, Ebright notes that construction on other high-risk labs is planned in Hamilton, Montana, at the NIAID Rocky Mountain Laboratory; in Fort Detrick, Maryland, with new labs there for the Defense Department, NIAID, and the Department of Homeland Security; and also in Atlanta, Georgia, for the CDC.

According to Ebright, this new BL-4 space will amount to between 200,000 and 300,000 square feet—10 to 15 times more than the amount of similar lab space being operated in 2001.

These concerns are heightened by the number of research personnel now approved for work with anthrax, plague, and other “select agents.” The CDC has inspected and fully certified 235 facilities and given provisional approval to 82 more, a spokesperson says. An official at the FBI’s Criminal Justice Information Services Division says the bureau has processed about 12,000 aplications to work with such agents.

Research on potentially dangerous organisms “isn’t just going on unfettered and unmonitored,” emphasizes Gerald Fink, Whitehead Founding Member and chair of the National Academies Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology. “The government is setting up a system to review it. Of course, the devil is in the details.”

As Fink’s committee advised last year, the government is establishing a National Science Advisory Board for Biosecurity. Managed by NIH, the new board is described as a critical component of a set of federal initiatives to promote biosecurity. It will provide security guidance and leadership about dual-use bioresearch (studies with legitimate scientific purpose that may be misused to pose a biological threat).

Draining the funding pool?

Ebright and other opponents of the biodefense effort say that it will end up siphoning away federal support for basic scientific studies in other biomedical areas that affect the health of tens of millions of people. “There’s a tremendous waste of funding,” declares Ebright.

Since 2001, Ebright says, biodefense has seen the largest targeted increase in any research area at an NIH institute in the history of NIH—higher growth than the buildups for the War on Cancer and for HIV/AIDS. “No agency at NIH can absorb a targeted increase of that magnitude without effectively eliminating peer review,” he maintains.

Other scientists, such as world-renowned microbiologist Stanley Falkow at Stanford University, also worry that this strategy could cut funding for other disease studies.

“It’s going to be done at the expense of some organisms that are causing serious health problems in the United States but are not getting the same emphasis, like drug-resistant staphylococci, pneumococci, and the like,” says Falkow. “There’s a need to be vigilant about biodefense, without any question,” he adds. “On the other hand, I think, in part, the current response is one that is dictated by political reasons rather than scientific reasons.”

“I don’t think anybody would argue that biodefense isn’t important, and certainly we learned that with the anthrax thing and 9/11. But we still have 1,500 people or thereabouts a day dying from cancer,” says Wendy Selig, vice president for legislative affairs at the American Cancer Society. “Pressure on the budget, forcing these arbitrary ceilings on spending, is causing very difficult choices.”

One potential indicator of this stress: Following a five-year period in which funding for the National Cancer Institute jumped by 81 percent, the institute received only a 3.9 percent increase in 2004.

Doing double duty

NIAID chief Anthony Fauci, a key architect of the current biodefense effort, flatly denies that politics are driving research or that the program has reduced allocations for other areas of biomedical research. “It is brand new money,” he insists. “It wasn’t money that was moved around from one research direction to another.”Fauci also emphasizes that the research being supported is dual-purpose.

“Because of the threat of bioterror on this nation, we need to be prepared from the standpoint of understanding the microbes that could be used and developing countermeasures, which is probably the most important component of the research,” he says. But he maintains that programs to study naturally occurring infectious diseases also will play a significant role.

“In fact, a naturally evolving catastrophic epidemic is incredibly more likely than a deliberately released one,” Fauci says. “The intellectual capital, the resources, the amount of effort you put into understanding the natural evolution of microbes is absolutely complementary to work that’s done on trying to develop countermeasures for deliberately released microbes,” he emphasizes.

Infectious-disease specialist Cross agrees, saying that the biodefense program is spinning off some very good basic science, pointing to advances such as sequencing the whole genome of the anthrax bacillus. “We have a whole new database to work with,” he says. “We have a whole new concept of how toxins work.”

Additionally, the University of Maryland researcher says he isn’t particularly concerned about the possibility of draining down money for other fields of research. “Obviously, there is a limited pot,” he acknowledges. “Some choices will have to be made.”



Communications and Public Affairs
Phone: 617-452-4630

Related News