When Bioterror Moves Next Door
It will be one of the safest and most hazardous places on earth, right in the heart of Boston, a laboratory to combat pathogens like Ebola, smallpox, and anthrax. Scientists are calling it a biosafety lab, but others warn that it's a bioterror lab. So which is it?
Deep within the US Army Medical Research Institute of Infectious Diseases in Frederick, Maryland, a maze of hallways, done up floor-to-ceiling in gradations of beige, leads to a wing called "the slammer." The two-room isolation ward on the Fort Detrick base takes its name from the unnerving clank that the reinforced-steel air lock makes as it seals behind you. It sees very little action. When it does, something has gone very wrong. Last winter, the ward saw its first patient in nearly 20 years after a young researcher pricked herself with an Ebola-tainted needle while experimenting with the deadly virus in one of the facility's maximum-containment, level-4 biosafety laboratories -- known as "hot" labs. She spent the better part of February in quarantine, her only face-to-face contact coming with the medical personnel, clad in protective gear, who periodically shuffled in to monitor her condition. She exhibited no symptoms during her three-week internment. No longer a threat to her colleagues, family, or the surrounding community, the young woman returned to work. She was lucky. Months later, in May, under similar circumstances -- Ebola, a needle prick -- a Russian researcher perished slowly in isolation as fever gave way to vital organ failure, then to unfettered internal bleeding.
In a nearby wing, a dim corridor is lined by laboratory suites, some of these also housing hot labs, where researchers explore the deadliest microorganisms known to science -- germs of unknown or lethal pathogenesis, some of which spread easily on air currents. The work is dangerous. But the risk, such researchers would say, is outweighed by the perils of inaction.
In the early 1980s, Boston University microbiologist John R. "Jack" Murphy conducted a study that had been assigned to the research institute at Fort Detrick, home to one of the nation's few level-4 labs. Using the emerging technology of genetic engineering, Murphy led a team of Harvard scientists who sought to insert segments of diphtheria genes into E. coli to create a new, lethal toxin. The goal: forge a hybrid gene that would target malignant cancer cells. The risk: engineering not a new weapon against disease but a new and deadly disease in itself.
"It was never done before," Murphy says. "There was no precedent." Murphy himself didn't know what would happen. "There was a natural level of skepticism and concern that what we were going to make would be truly dangerous," the 62-year-old researcher recalls. Reading from a news clipping from 1982, he quotes a colleague who forecast catastrophe: "Even if the risk is small, this experiment is potentially deadly to every mammalian species on the planet. This means that it's more dangerous than a nuclear weapon, if the risk realizes its potential."
And yet his controversial work led to the discovery of the cancer-fighting drug Ontak, approved by the US Food and Drug Administration five years ago.
Murphy will soon conduct research in a level-4 lab again. The facility will be blocks from his South End apartment and steps from his current office in the Evans Biomedical Research Center. On the future lab site, a parking lot now sprawls for a half block on Albany Street, causing a gap in the industrial landscape where the Boston Flower Exchange leaves off and the Boston University Medical Center's campus begins. Pending environmental impact reviews, work on the facility should be underway by next summer. Heavy machinery will speckle the grounds, and construction crews will pour a foundation. Day by day, the skeleton of what will become a vast laboratory complex will take form. It will be, at once, one of the safest and most hazardous places in North America.
BY THE WINTER OF 2007, Murphy will stroll to work through the tony back streets of his neighborhood and approach an 8-foot-high wrought-iron fence -- designed to blend elegantly with nearby row houses and yet withstand the impact of a speeding truck, according to Kevin Tuohey, Boston University Medical Center's operations and public safety chief. At the entrance, Murphy will widen his eyes for an iris scan and push through a turnstile into a grass courtyard patrolled by armed guards. Entering the eight-story National Emerging Infectious Diseases Laboratories, Murphy, the facility's associate director, will navigate a succession of security checkpoints to reach a restricted area.
Murphy will enter a change room, strip naked, don scrubs, and coax his body into a white, self-contained suit of thick plastic. Passing through a submarine-style air lock, he will enter a hot lab. Surrounded by modular stainless-steel workbenches, refrigeration units, and plexiglass-hooded biosafety cabinets, he will pull a coil from the ceiling, attach it to a duct on his suit, and brace for the rush of cool air that expands the suit like a balloon. The laboratory itself will be under negative pressure, drawing air in, not out; a high-efficiency particulate filtration system will trap microscopic airborne contaminants. Here, the order of the day will be Ebola, Marburg, Lassa, or a challenge experiment with aerosolized anthrax.
To most, the mere mention of such killer pathogens inspires fear, but the forces of nature have always beguiled Murphy. He grew up in Greenwich, Connecticut, racing sailboats on Long Island Sound. These days, he's supervising student researchers, crafting grant proposals, and planning for BU's new lab, where, in addition to his administrative duties and his own research, Murphy will use the facility's level-4 lab to oversee the growth of virulent organisms to be used for research.
Last fall, the National Institute of Allergy and Infectious Diseases (NIAID) selected BU, where Murphy has been a professor of medicine and microbiology for 21 years, as one of two institutions that will construct national biocontainment laboratories. Both labs will take a lead role in the nation's biodefense effort. Housing level-4 labs, operating at the highest biocontainment designation, as well as level-2 and level-3 containment suites, the facilities will join an elite group of labs, five currently, that take on such dangerous work. In a region that boasts many pillars of academia, BU's lab will elevate its prestige dramatically. "It will make us more competitive," says BU's interim president, Aram V. Chobanian. "In the areas that we're talking about" -- infectious diseases -- "it will make us the leading institution."
Support for the project has not been in short supply. With $128 million in federal funding pledged to offset total project costs of $178 million for BU's lab and $2.9 billion more expected to pour into the facility over the next two decades, political leaders of all ranks offered their backing, maintaining that the project will boost the city's economy and solidify Boston's standing as a biotech hub.
The facility will be a magnet for scientific talent and create an estimated 660 permanent jobs, BU says. Consequently, it has proved an easy sell to elected officials, including Mayor Thomas M. Menino, Governor Mitt Romney, and Senator Edward M. Kennedy. "We have the best scientists in the world," says US Representative Michael E. Capuano, whose district includes the South End. "This is just a natural extension of our current economic engine. I think it fits in well."
From a national perspective, the facilities, the second of which will be built at the University of Texas Medical Branch in Galveston, are symbolic of Bush administration policy in motion. The events of 9/11, and the subsequent scourge of anthrax-filled letters, opened the nation's eyes to the menace of terrorism. As a result, the administration of George W. Bush stepped up research programs to explore countermeasures to weaponized pathogens. Universities across the country were enlisted to join the effort.
To Murphy, BU's biolab is a matter of life and death. Scores of critical projects are in limbo for lack of level-4 facilities, he says. One such study belongs to Robert Finberg, chairman of the University of Massachusetts Medical School's Department of Medicine, who works with hemorrhagic fever viruses, including Ebola and Marburg. With a mortality rate reaching 90 percent, Ebola and its less lethal cousin Marburg were among a laundry list of biological agents explored by the Soviet Union for offensive purposes during the hey-day of the USSR's bioweapons program.
At the moment, Finberg can't use live virus, and any work originating at his lab that requires maximum containment is outsourced to the already backlogged US Army Medical Research Institute of Infectious Diseases at Fort Detrick. Once built, BU's lab will host his research. Finberg doesn't see his work as crucial to national defense. To him, it's just science. "I think we're going to learn amazing things," he says. "Do I think it's going to cure the problem of terrorism? No. That's a political problem."
"INCURABLE DISEASES. That's all I really need to know," says Klare X. Allen, a mother of four who wears graying dreadlocks and lives several miles from the lab site, near Roxbury's Egleston Square.
Allen is the community organizer for the Roxbury-based environmental advocacy group Alternatives for Community & Environment, which occupies a loft in an office building in Dudley Square. Until recently, the nonprofit was best known for thwarting plans to build an asphalt batching plant in South Bay. Now ACE, with its 11 staffers and shoestring budget, is known as BU's most stubborn antagonist.
The quickening pace of development all across Boston has left Allen's neighborhood increasingly gentrified. Her cramped first-floor apartment now goes for $1,400 a month, up from $800 four years ago. In another four years, her family may no longer be able to afford to live there. To her, "the man" -- a catch-all term she invokes often to describe forces beyond her control -- is very real. It's the pervasive sense that her voice and that of her neighbors frequently go unheard.
As new projects have threatened to encroach -- be they batching plants or condominium complexes or biodefense labs -- community members like Allen have learned to view commercial development with skepticism, if not outright suspicion. The fight against BU's lab is reminiscent of a struggle faced by Cambridge residents 20 years ago, when the consulting firm Arthur D. Little, under contract with Department of Defense, began exploring countermeasures to chemical weapons, including sarin and VX nerve gases, at its Cambridge facility. For two years, critics argued forcefully that the chemical agents, if accidentally released, could endanger residents. In 1985, a Massachusetts Supreme Judicial Court ruling blocked the company's heavily protested nerve-gas testing. Taking their cue from the successful movement against Arthur D. Little, Allen and other activists believe the route to derailing BU's biolab lies in sustained protest. Failing that, ACE intends to file a lawsuit to stop the project.
In a conference room where ACE has organized its resistance, a crinkled poster fixed to the wall reads "Possible Tactics." A list of entries, scrawled in black marker, follow: "Get people mad," "Report that BU lied," "Protest at BUMC," "Put word on Internet." As the organization's yearlong campaign against the biolab has unfolded, it has followed through, with varying levels of success, on all of the above.
From the beginning, says Penn Loh, ACE's 35-year-old executive director and an MIT-trained electrical engineer, "the strategy was to try to raise as much doubt at [NIAID] that this would be a hard facility to get built in Boston, because of the opposition."
The roots of the opposition began at a public meeting on May 12, 2003, at BU Medical Center, presided over by Dr. Mark S. Klempner, the center's associate provost for research, and attended by members of Safety Net, a neighborhood coalition founded by Allen. Klempner, who will direct the National Emerging Infectious Diseases Laboratories at BU, is a well-regarded physician known for his Lyme disease research. He exudes an air of self-assuredness that reads, at times, as arrogance. According to community activists at the meeting, Klempner was evasive when answering questions about the project and condescending to Safety Net members. "Whenever he talks, there's china breaking all over the world," says BU epidemiologist David Ozonoff, who attended that spring meeting where Klempner spoke. "From a public relations standpoint, it's a catastrophe."
Klempner's slight, perceived or otherwise, unsettled those in attendance, as did BU's refusal to release its grant application for the project. When the university released a redacted version in April, removed were details of some of the experiments planned for the facility. Klempner asserted at a private briefing in late March with City Council members that a federal Freedom of Information Act request in October 2003 hampered the document's release, though a spokes-person for the NIAID disputed this claim. BU had been free to issue the proposal at any time, the spokesperson said. Within weeks of the meeting, ACE and Safety Net members had blanketed their communities with fliers, warning of the pending "bioterror" lab.
Among detractors, the perception grew that the lab project was a done deal from the start. Indeed, according to internal memos, the Boston Redevelopment Authority began paving the way for the lab's development six months before BU's grant application was approved in September 2003. And Boston Public Health Commission executive director John Auerbach offered his agency's support in a February 2003 letter to BU, writing, "We look forward to participating in and supporting your application for this important national resource."
Lab opponents questioned the logic of locating a high-containment facility in a densely populated neighborhood, pointed out its potential as a terrorist target, and floated the possibility that under a cloak of secrecy, researchers would conduct nefarious experiments, perhaps even creating deadly lab-altered germs. When word spread of how pathogens for study would be conveyed to and from the facility, concerns grew. Federal guidelines require that such deliveries are boxed in triple-layer packaging; they are transported by conventional services such as FedEx, DHL, and the US Postal Service. BU's lab will receive roughly two or three deliveries monthly. Such shipments, according to the university, will be highly coordinated, routed on highways, not city streets, and monitored by a global positioning system (it will activate an alarm should a parcel stray from its course). BU's Tuohey says of such a package: "I'll know when it's coming, I'll know where it is, and I'll know who's delivering it."
Still, there have been mishaps -- mishaps that BU's safety precautions probably wouldn't prevent.
On March 18, 2003, at a FedEx depot in Columbus, Ohio, a parcel from the Ohio Department of Health containing West Nile-infected bird innards exploded, scattering the contents of one of eight vials. Fifty workers were evacuated as a hazardous-materials crew descended on the depot, containing the situation without incident.
This June, due to an error by a company that shipped anthrax to Children's Hospital Oakland Research Institute, eight researchers were placed on a precautionary course of Cipro following their potential exposure. Believing they were working with deadened bacteria (the type they ordered), the researchers explored what was in fact live agent under minimal containment.
AFTER BU RECEIVED the federal nod to build the biolab, doubts about its safety lingered. On the evening of December 10, 2003, Menino convened the first citywide forum on the facility, at the Boston Public Library. The task of presenting the details of the national biocontainment laboratory to the restless crowd of 350 fell to Jack Murphy. "No place on this planet is more than 36 hours away from any of us," he began. "This means that a person, exposed to Ebola virus or any other emerging infectious diseases in a distant land, on an airplane, can be in the city of Boston, amongst all of us, within 36 hours."
Even as Murphy stressed the research imperative for the lab, a scenario similar to the one he warned of was playing out in a distant land.
Near 1 p.m. Taiwan time, China Airlines flight CI-662 touched down in Taipei, carrying 44-year-old Lieutenant Colonel Chan, a military researcher who was returning home from a three-day scientific conference in Singapore. That evening, he ran a mild fever. Experiencing flulike symptoms the following day, Chan, a senior scientist at Taipei's Institute of Preventive Medicine, stayed home from work. Over the next few days, his condition worsened. His breathing became labored; bouts of diarrhea left him dehydrated and weak.
On December 16, persuaded to seek treatment, Chan was taken to a hospital, where SARS (Severe Acute Respiratory Syndrome) was confirmed. In the days that followed, officials in Taiwan and Singapore tracked down more than 100 individuals who came in contact with Chan since the date of his suspected exposure on December 5, placing many under quarantine. By January 1, Chan had recovered, and no other cases had been reported.
However, nearly six months after Chan fell ill, Chinese officials declared a SARS outbreak in mainland China, also linked to a lab where the virus was under study this time, with deadly consequences. (Chinese authorities have identified the victims, as in Chan's case, solely by their surnames.) Within a month of each other this spring, 26-year-old Ms. Song and 31-year-old Mr. Yang, graduate students working at the Chinese Center for Disease Control's Institute of Virology in Beijing, presented symptoms of SARS. While Yang's case was caught quickly, and the researcher quarantined, Song traveled by train twice between Beijing and her mother's home in Anhui province while infected. Through close contact, she passed the virus to her mother and to a young nurse, Ms. Li, who tended to Song in a Beijing hospital. Unwittingly infected, Li transmitted SARS to five others, her mother, father, and aunt among them. Song's 53-year-old mother died on April 19.
WHEN CITING the hazards of high-containment research, MIT molecular biologist Jonathan King tells of the SARS mini-epidemic and the near-miss in the case of Chan. Asked whether lax safety protocols contributed to the containment failures, as some assert, King says, "I don't think there's a shred of evidence that sterility, that cleanliness or safety standards are lower" in Taiwanese or Chinese labs. "You have these outbreaks in contained facilities where everybody there is a professional. And is it an explosion? No, it's person-to-person transmission."
The tall, shambling professor is part of a cadre of local scientists and academics that has lambasted BU's lab on the grounds that it will be neither safe nor of any benefit to public health. He added his name to an open letter, sent in April and signed by 146 other scientists, professors, and public health specialists, requesting that BU rescind its plans to build the laboratory. "There are real and potentially catastrophic risks to the health and safety of people in the local and surrounding communities," the letter stated.
After letters carrying anthrax spores arrived at news outlets and congressional offices, among other locations, in September and October 2001, killing five and infecting 17 others, the Bush administration responded by pouring a Niagara of funding -- more than $10 billion to date -- into biodefense research. The National Institutes of Health, the arm of the Department of Health and Human Services that oversees the National Institute of Allergy and Infectious Diseases, has seen its biodefense budget soar, from $53 million in 2001 to $1.6 billion in 2004. In addition to sponsoring research nationwide, federal funds will buy at least three new level-4 labs, not including those planned for BU and the University of Texas: one in Hamilton, Montana, on NIAID's Rocky Mountain Laboratories campus; and two at Fort Detrick, one apiece for NIAID and the Department of Homeland Security.
"I'm assuming the reason this nation has put so much money into biodefense preparedness is not that it's terribly likely to occur but that we can't measure the risk, and, critically, the potential outcome is so enormous," says retired Army colonel David R. Franz, former head of the US Army Medical Research Institute of Infectious Diseases. Franz, who served three tours as a United Nations bioweapons inspector in Iraq, continues: "We had to respond, I think, vigorously as a nation."
Richard H. Ebright, a professor of chemistry at Rutgers who heads a protein biochemistry lab, argues that the biodefense boom will increase the likelihood that a biological attack will originate from within our borders, perhaps using germs cultivated in US labs or the know-how derived therein. "This does not make sense," he says, "no more than increasing the number of flight schools, increasing the number of flight-school trainees, and developing advanced tactics for air piracy would make sense as a response to 9/11." He adds, "We're spending money to increase our vulnerability."
Some researchers also worry that the federal emphasis on biodefense is diverting funds from research exploring imminent health threats AIDS, West Nile, avian flu and gutting financial support for the public health sector. "It's like the guy who goes to the gym every day and exercises his right arm, which hypertrophies gigantic muscles, and the rest of his body atrophies," says BU's Ozonoff, who chaired the environmental health department for 25 years, until June 2003. "That's what's happening to public health."
Ozonoff began as a supporter of the biolab. "I really think I was seriously misled," the epidemiologist says. The laboratory, as it was first presented to him in informal conversations with Klempner, was to focus on high-risk emerging infectious diseases, Ozonoff says. He was told the university would have full control over the research agenda, a position that BU officials still contend. BU's lab, however, has a clear biodefense mandate, according to the federal solicitation for the proposed facility, and will operate under the oversight of NIAID for a minimum of 20 years.
Ozonoff now believes the facility could become a bastion of secrecy where federal agencies, including the departments of Defense and Homeland Security, will sponsor experiments with deadly pathogens outside the scrutiny of public view. The lab will be open for work conducted for such agencies, but currently not even the US Army Medical Research Institute of Infectious Diseases engages in clandestine work, according to spokes-woman Caree Vander Linden of USAMRIID.
NIAID does not now support classified research, but given the sensitive nature of biodefense work and the potential that published findings could serve as a how-to for terrorists, it cannot preclude that possibility. "If I could predict the future, I wouldn't be in this job," says Rona Hirschberg, a senior program officer for the institute. "There are no plans to do that kind of work." At BU, everyone connected with the project who spoke for this article flatly denied that any secret research would take place in its lab.
ON APRIL 28, announcing the president's classified biodefense directive, Department of Health and Human Services Secretary Tommy G. Thompson told reporters: "We know that terrorists want to do everything they can to harm Americans, and they could be creative in their use of new or different biological agents. We're working to stay a step ahead of those who would harm us. ... We're taking into consideration the possibility of new or genetically engineered agents."
Some observers believe biodefense researchers, in the name of counterterrorism, could be called upon to use recombinant methods like gene splicing and shuffling DNA molecules to make pathogens more potent and transmissible or resistant to available therapies, or even to engineer new strains and then work in reverse to explore countermeasures. Such pursuits are not without precedent.
Last October, researchers at Saint Louis University announced that they had engineered a supervirus, a strain of mousepox, kin to the lethal smallpox, that was resistant to antiviral drugs and vaccination. The study, a re-creation of an Australian experiment two years prior (termed an accident then), was carried out to explore avenues of countering bioterrorism and was funded by NIAID.
But Jack Murphy, the associate director of the planned lab at BU, likens the prospect of out-thinking terrorists to the efficacy of summoning spirits on a Ouija board. "It's not our business, pure and simple," he says.
Despite the stated defense-oriented objective of BU's lab and the fact that it will be considered a "national resource" by the federal government, Murphy doesn't think of it as a "biodefense" facility. It will be a place, he says, for the study of emerging and re-emerging infectious diseases (those occurring naturally and those introduced deliberately). To Murphy, the government's sudden focus on biodefense is a moment to be seized upon, and BU's lab, in turn, can use it as an opportunity to advance science beyond the status quo.
AS MUCH AS RESEARCH is propelled by the higher laws of science and the spirit of discovery, so, too, is it swept along by political and economic undercurrents. Policy determines government funding; researchers follow the money.
Thirty-two years after Richard Nixon declared war on the "dread disease" cancer during his 1971 State of the Union address, President George W. Bush, ramping up for war with Iraq, warned the American public that "chemical agents, lethal viruses, and shadowy terrorist networks are not easily contained. Imagine those 19 hijackers with other weapons and other plans -- this time armed by Saddam Hussein. It would take one vial, one canister, one crate slipped into this country, to bring a day of horror like none we have ever known."
With the war on terror now nearing the start of its fourth year, Murphy's research, which once yielded a cancer treatment, now shows promise of providing a therapy for pulmonary anthrax -- the variety that killed five in 2001.
In the coming years, the nation's biodefense infrastructure will expand exponentially. With it not only grows the likelihood that new treatments for diseases and cures for infectious pathogens will be discovered, but also the possibility that the rapid escalation of the US biodefense program will endanger those whom it purports to defend.
Murphy can't say there's no risk a pathogen could escape BU's lab by accident or intent, only that such a possibility will be reduced through engineering, tight security, and stringent safety protocols.
Seated in his office, the researcher holds out his hands, palms up, and weighs the possibilities. One hand holds the prospect of defeating the world's deadliest blights, the other carries the inherent dangers such work necessitates. "Risk and benefit," he says, as the imaginary scales teeter, then settle in favor of scientific progress.
Some, however, will never accept acceptable risk. Construction on the lab is still slated to begin by next summer. If it does, says ACE's Klare Allen, "the only thing we can do is put our bodies in front of the bulldozer."
Daniel Schulman is a freelance writer who lives in Cambridge. Adam Smith is the co-editor of Sampan, a Chinese-English newspaper in Boston.
© Copyright 2004 Globe Newspaper Company.