Bugs in the system

Unlike the instant and obvious horror of an airplane hijacking or a bomb blast, the telltale signs of a bioterrorist attack — especially in the immediate aftermath — can be far more difficult to ascertain. To tell if an outbreak of illness is the result of a biological attack, scientists need to compile and analyze certain information such as who got sick, when, where and with what.

Prompt analysis could help pinpoint the source of any outbreak, predict its course and help stem its spread. The needed technological tools, however, are still under development.

Military labs, federal health agencies and private firms are working to develop systems for rapid diagnosis and dissemination of information to help investigate and possibly limit the effects of an outbreak, but a great deal of work still remains.

The Bush administration has proposed $6.98 billion in fiscal 2005 for biodefense-related programs across the federal government. That includes

$274 million for a Bio-Surveillance Program Initiative. According to Homeland Security Department officials, the initiative will, among other things, require DHS to create a system that will integrate a broad variety of bioinformatics data from across the government.

Medical early warning

One example of the research and development occurring across government and the private sector is the Army Biological Defense Program at the Army's Edgewood Chemical Biological Center at Aberdeen Proving Ground, Md., where officials are seeking to develop predictability tools that can detect human susceptibility to toxins.

A good analysis tool certainly helps, but it has to be paired with a well-

designed response plan, said Jennifer Nuzzo, a research analyst at the University of Pittsburgh Medical School's Center for Biosecurity in Baltimore. She said there is an urgent need for valid data collection programs and also a rapid response system to use the data, driven by specialized software.

Along these lines, scientists at the Walter Reed Army Institute of Research in Silver Spring, Md., are using existing military medical records and newly developed software in hopes of creating early notification systems for an epidemiological outbreak.

Lt. Col. Julie Pavlin, chief of the institute's Department of Field Studies, has written that a biological attack "may not follow an expected pattern. Furthermore, a small outbreak of illness could be an early warning of a more serious attack, and recognition and prompt institution of preventative measures — such as effective vaccines and antibiotics — could save thousands of lives."

To collect and collate epidemiological data, programmers at the institute have developed the Electronic Surveillance System for the Early Notification of Community-based Epidemics, or ESSENCE-4. The system also uses some Java-based software written with the help of the Johns Hopkins Applied Physics Lab in Baltimore.

Pavlin said the program gathers information anonymously from the Defense Department and the Department of Veterans Affairs. "Every time someone comes in for a visit there's a set of international diagnostic codes that are used for all complaints," she said. "We take certain ones that represent infectious diseases — like respiratory illnesses, gastrointestinal fever — and group them into specific categories such as respiratory, neurological and so forth."

ESSENCE-4 monitors the data by time, number of visits and the various locations for the different disease categories. Using specific algorithms, the data can provide epidemiological information not normally available — for example, respiratory infection rates in a specific state.

"You can use this epidemiological data, compare it to previous times and see if there really is something abnormal for this time of year or this season and we should investigate," Pavlin said. "The data also includes the age of the patient [and] the ZIP code, so you can get a feel for what kind of people are being infected."

CDC's multipronged effort

The work at Walter Reed is being augmented at the Centers for Disease Control and Prevention in Atlanta. The BioSense Project there — a broad national biosurveillance initiative — adds anonymous civilian medical data to the gathered military data.

BioSense is the early-event detection component of CDC's Public Health Information Network (PHIN). PHIN also includes:

BioWatch — a network of 4,000 atmospheric monitoring stations nationwide scanning for atmospheric pollutants.

BioShield — a program to develop vaccines and treatments.

"From the standpoint of biosurveillance, [BioSense's] target is to minimize morbidity and mortality," said Dr. John Loonsk, associate director for informatics at CDC. Other targets include early detection, location, quantification and causation of events, and whether they are natural or man-made epidemiological outbreaks, including bioterrorism.

Phase I of BioSense went into effect last October at about 20 U.S. locations that Loonsk declined to name, citing national security. Using Web-based software, Phase I provides public health officials with data relating to possible bioterrorism in their jurisdictions from national health care sources, such as VA and DOD medical treatment facilities and national clinical labs.

"In addition to having high-speed Internet connectivity, we layer a secure network on top of that," he said.

The next step will be to connect relevant regional data from hospital systems, health plans and local clinics. BioSense is not collecting all relevant data, Loonsk admitted, partially because federal and state health care systems do not uniformly record or share data.

BioSense is "not about a single software system," Loonsk said. In the context of this initiative, he added, some of it is commercial off-the-shelf software, and some of it is being developed specifically for the system.

Special software needed

The National Institute of General Medical Sciences (NIGMS) — a component of the National Institutes of Health, which spends almost $30 billion a year on research — founded the Center for Bioinformatics and Computational Biology last year. NIGMS officials are creating eight NIH National Centers for Biological Computing. Among other activities, the centers will develop a national software engineering system and computer simulations of everything from molecular biology to infectious diseases and bioterrorism threats.

"Our role is to build the software that will run on a national computing grid and deliver to everyone what they need," said Dr. Erik Jakobsson, the center's director. He added that computing has become integral to all leading-edge biomedical research, but the needed software "has grown kind of haphazardly. A lot of it is stuff that has been written in people's labs, and nobody else can quite use it."

"With a few exceptions, the software has not really been engineered as professional software should be," Jakobsson said. "And the commercial companies have not gotten into it because you don't have the mass market for biology research software that you do for [Microsoft Corp.'s] Windows operating system and for Office tools. Yet, it's got to be done because we have this enormous enterprise."

He said that a good deal of biomedical computing software is designed by a small group of people working to solve particular problems.

"This is very different from software which is designed for very wide dissemination on the part of lots of people," he said. "What we're really talking about is not so much anybody having made mistakes [in creating software] as having the need now to go to the next stage in the evolution of biomedical computing software technology, to have it move from being specialized code that is used by research groups interested in very particular problems to being more generally used as an adjunct to other techniques in everybody's laboratory."

An announcement on the venues for the eight centers, to be funded initially at $4 million a year, is scheduled for September. "The charge to the centers is to develop, to build into robust software [and] to disseminate for the nation, appropriate software environments [and] to do outreach in making sure people know how to use the software effectively," Jakobsson said.

The centers and software design work will be done outside NIGMS, through grants from NIH. "Whether or not the successful grantees will have some private-sector component is not clear," he said. "We will have to see who rises to the top of the selection pool."

The National Centers for Biological Computing is one of two current NIGMS initiatives. The other is the Models of Infectious Disease Agents Study (MIDAS).

"We don't now have a single information [collection] environment for infectious diseases," Jakobsson said. He wants researchers to have all the necessary data and modeling tools at their fingertips to understand what is likely to happen in the course of an infectious outbreak.

In May, NIGMS awarded the first four grants for MIDAS, totaling more than $28 million over five years (see box, Page s32). Three of the grants will support the creation of mathematical models to study various aspects of infectious disease epidemics and community responses.

Another award, totaling $18.8 million over five years, will enable researchers to develop a central database to organize information from the other groups. It also supports the development of computer modeling tools for the broader scientific community,

policy-makers and public health officials to use to simulate epidemics and response strategies.

Industry assistance

Federal efforts at boosting bioinformatics technology are also being augmented by the private sector. Officials at IT services provider SRA International Inc. are hoping to win some federal contracts to create software that will collect and analyze data on patterns of infection or bioterrorism.

"A lot of [this work] is very novel, a lot of it has never been tried before," said Susan Castillo, bioinformatics account manager at SRA. "Right now, it's done in individual laboratories and even in individual machines."

Meanwhile, Northrop Grumman IT Health Solutions officials are evaluating results of a Bioinformatics Support Contract from NIH's National Institute of Allergy and Infectious Diseases to provide advanced information technology support for researchers. The contract calls for, among other things, prototyping a system for the collection, storage and querying of data, and designing, implementing and maintaining a data warehouse.

"Our initial work was a requirements analysis and then putting together software as a prototype system," said Robert Cothren, chief scientist of the health solutions division.

In the next phase, NIH will award contracts that include designing and building multiorganism databases, especially those related to biodefense, and developing specific analysis tools.

It will become one more part of a patchwork of interrelated systems designed to counter and minimize the consequences of bioterrorism attacks.

Hubler is a freelance writer and editor based in Annandale, Va. He can be reached at [email protected]


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