Courtesy of Pedro Scassa
Valley Fever, a pneumonia-like lung disease that strikes 50,000 people each year, has become an epidemic in southern Arizona, and John Galgiani, director of the University of Arizona's Valley Fever Center for Excellence in Tucson, wants to know why. But the research that might help this microbiologist uncover the state's Valley Fever mystery has been brought to a halt by the very agency, the Centers for Disease Control and Prevention, charged with protecting people from disease. The CDC's new regulations for transporting and handling potentially deadly pathogens has so burdened the labs that once supplied Galgiani with strains from sick patients, the labs are destroying the samples rather than sending them to him.1
Nearly two years after Congress tightened the laws for its select agents, scientists and academics have endured unprecedented scrutiny: lab inspections, FBI background checks, inventory requirements, and security equipment installations. At best, that scrutiny has merely caused researchers inconvenience. At worst, it has resulted in enough cost, delays, and invasion of privacy to persuade some to abandon work on select agents, while giving others pause before embarking on careers in the field.
Some scientists applaud the new laws. Paul Keim, principal investigator on dangerous pathogens at Northern Arizona University in Flagstaff, says tighter select-agent laws are probably worth the headaches. "While there are problems associated with this, I think the law is pretty reasonable," he asserts.
Stephanie Loranger, who works on biosecurity issues for the Federation of American Scientists, says she has talked with many researchers who are happy about the new laws. "They seem to be saying this is a national security imperative," Loranger relates. "And they are actively pursuing this research because of all the new money that's gone into it."
But plenty of researchers say the new laws have cost so much money, time, and delays that they wonder if working with select agents is worth the trouble. Some have questioned the expertise of CDC inspectors. Others fear that researchers frustrated with the new laws will destroy bacterial strains that might offer clues to protecting people from disease. Still others warn that the new laws discourage promising young scientists from studying the pathogens.
"These regulations were put in place with extremely good intentions," says Julie Fischer, a research fellow who is studying the impact of the new biosecurity regulations at the Henry L. Stimson Center in Washington, DC. "But we need to seriously consider the impact. Is it reasonable to say there will be some inconvenience and invasion of privacy, and if so, how much? As a scientific community, and as a society, we must make a conscious decision about what trade-offs are acceptable."
Prior to Sept. 11, 2001, researchers were required to notify the government each time they transferred dangerous pathogens. The Public Health Security and Bioterrorism Preparedness Response Act of 2002 now regulates not only the transfer, but also the possession and use of select agents. Transport rules now require permission from the CDC, not just notification, and mandate that researchers carefully document their paper trails.
Courtesy of Theresa Koehler
More than 800 government agencies, universities, research institutions, and commercial entities that work with select agents must register with the CDC, the US Department of Agriculture (USDA), or both, which involves lab inspections, costly security requirements, and painstaking inventories of each agent on hand. Moreover, anyone who comes in contact with any of the 80 bacteria, viruses, or toxins now on the government's select-agent list must undergo thorough and sometimes lengthy FBI clearances involving fingerprinting, criminal checks, personal questionnaires, and the interviewing of people who know the applicant.2
Before the September 2001 terror attacks, it might have taken a day or two for Theresa Koehler to transfer select agents from her University of Texas lab to an outside lab. Koehler, a bacterial geneticist who has studied anthrax for more than two decades, tried to do such a transfer last year, and it took five months. "This delays knowledge," Koehler says. "It impedes progress. Ultimately, it can affect grants and publications."
Fischer says the new inventory and security requirements have placed tremendous burdens on researchers. Labs must now record each instance that someone handles a select agent, including the date, the researcher's name, the name of the agent, the amount of toxin removed from storage, and the amount returned. CDC inspectors who examine select-agent labs typically require security cameras, badge access, and records of who enters the labs, and when. Such requirements can cost tens of thousands of dollars.
Many labs hire at least one full-time person to handle the new regulations, Fischer says. Some have hired as many as three. To be on the safe side, some labs now require researchers to work in "buddy systems," an arrangement, Fischer says, that "can halve your productivity." In some cases, the institution supplies the money for new security requirements and staff. In others, scientists use money from their research grants.
Louisiana State University, Baton Rouge, reports spending $130,000 (US) to increase security at its labs. Keim, at Northern Arizona, says it cost $150,000 for the staff time, security equipment, and computer programs required to inventory and secure his pathogens properly. Some researchers aren't convinced that the costs and effort are worth it.
Jeffrey Frelinger, chairman of the microbiology and immunology department, University of North Carolina at Chapel Hill, reports that the CDC inspectors demonstrated "a great deal of concern about physical security and inventory control, but were unable to understand that biologicals can self-replicate." He explains, "If you have a virus or bacterial stock, you can grow any amount from an amount you can't possibly miss. You can't inventory sufficiently enough to know that." He adds, "I don't think [CDC inspectors] understand what the real issues about biologics are."
Courtesy of Peter Jahrling
Ted Jones, the CDC's acting director, says his inspectors are either "people with very strong science backgrounds" or microbiologists. "The select-agent program has the very best mechanisms to protect from both a safety and security standpoint," Jones says. "But as most reasonable people know, if someone wants to defeat a security or safety system, they can."
Background checks are now required for anyone who handles select agents, from secretaries who do shipping to researchers in the lab. In labs where perhaps two or three researchers previously had to get government clearance, dozens more are often now required to do so.
Tamas Torok, a lead researcher at the Lawrence Livermore National Laboratory in California, assumed that because he got government clearance years ago to work with select agents, getting clearance under the new regulations would be easy. "Basically," he says, "we had to start from scratch." Torok submitted his paperwork in February 2003, but did not get clearance until fall 2003. He also found the background checks more invasive than he expected. "You say, OK, that's the price you have to pay for working with this organism. But I was not thrilled that somebody who doesn't know me may or may not allow me to work as a microbiologist."
A security clearance is valid for only five years. Moreover, one is required every time a researcher handles a new agent or moves to a new institution. Koehler's newest assistant, Kerrie Thomason, worked three years at a select-agent lab at Texas A&M University. She had undergone an FBI background check under the new regulations, but when she came to Koehler's lab three months ago, she had to get a new clearance. As of early April, the FBI had yet to approve Thomason, and Koehler suspects it might take many more months. "Until she is reapproved, she must always be accompanied in the lab," Koehler says.
BARRIERS TO BEGINNING
Working with select agents now requires two levels of scrutiny: First, the FBI must conduct a background check on each individual who will come in contact with a select agent. In addition, the CDC or the USDA must review each lab that will house select agents, a review that may result in new security and inventory requirements. The applications can be delayed or denied at both levels.
Monte McKee, head of the FBI unit in charge of the background checks, says the typical clearance should take 45 days. But, the sheer volume of applications that landed in McKee's unit in a short period of time (2,500 between September and November of last year alone) impeded his 11-member staff. The FBI has completed just short of 85% of its background checks (9,201 of the 10,725 applications it received by the end of March 2004), but more than 1,500 are still pending.
Courtesy of Paul Keim
McKee says the FBI has denied less than 1% (fewer than 92) of the applications; he would not provide details on the specific cases. The overwhelming reason for denial, he says, was a past conviction. People cannot work with select agents if they were convicted of an offense that carried a maximum penalty of a year or longer. The USDA could not provide information about denials by press time.
The CDC's Jones says almost 1,800 applications for background checks were eventually canceled, either because the agents or toxins in question were not on the select agent list, or because "someone decided they didn't want to work with the agents, and they withdrew their application." The CDC has approved 194 applications, and 20 are pending. Another 125 labs have provisional registration, a status the government granted after it failed to meet a Nov. 12, 2003, deadline for registering labs. Provisional registration allows work with select agents, but labs cannot transfer them. The CDC denied registration to three labs because of what Jones called "safety or security concerns." He would not provide details.
Even some labs with full registration find it easier to autoclave collections of select agents rather than keep them in inventory. Peter Jahrling is a senior research scientist at the US Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md. For three decades, he collected isolates of Venezuelan equine encephalitis from Central and South America. The virus is considered a key threat to national security, although such collections can be critical to diagnosing, drug testing, and tracing the outbreak of diseases.
As of last Christmas, Jahrling had perhaps 3,000 vials of the frozen virus. When he examined the new regulations, he found that each vial needed an identifying number, the entire collection was to be inventoried, and each use of a vial was to be documented. He destroyed the collection. "This is akin to putting a double-bolt lock on your front door and leaving a thumbnail latch on your back door," Jahrling says. "To adopt a system where you need to account for every vial in the freezer and its exact location is just a huge vulnerability. If I wanted to steal [the virus] ... all I would do is thaw the vial, take out a small quantity that nobody would miss, put it into a container, and walk out."
Courtesy of Stanley Falkow
Stanley Falkow, a Stanford University scientist who works largely with organisms of the typhoid, cholera, and dysentery group, destroyed his entire collected of
Galgiani has watched the number of Valley Fever cases rise steadily in southern Arizona, from 1,917 in 2000 to 3,133 in 2002. He collected strains of the fungus from labs that cultured the organism from patient samples, to help him confirm his theory that construction in southern Arizona is disrupting the earth and throwing spores into the air. But because the culturing labs must now ship isolates within just seven days of getting them, most labs are destroying the samples rather than deal with the time constraints, says Galgiani.
"If you're in possession of it longer than seven days, you're a felon and could be in prison. That discourages clinical pathologists from holding on to these more than a week. They can't justify the time and the shipping costs ... so they're all being autoclaved."
Indeed, Fischer says, many scientists do fear they will run afoul of the new laws. "This is paperwork that carries potential criminal penalties if it is filled out incorrectly," Fischer says. "Even scientists not unhappy with increased scrutiny fear they could accidentally fill out paperwork incorrectly, or fail to meet a regulatory requirement."