By Eve Jacobs

Defending our country—and New Jersey—takes on new meaning as biological and chemical weapons threaten our well-being.

More than 100,000 calls come in yearly to New Jersey’s only poison control hotline, located behind the last door of a dim hallway in the former Martland Hospital on Bergen Street in Newark. Not even a creative genius could mentally transform this drab space into a stage where grave, sometimes life-or-death dramas are played out.

A toddler drinks Drano. A 15-year-old downs some unidentified pills sitting in the medicine cabinet. A young man is bitten by a neighbor’s pet snake. A car mechanic spills a caustic chemical on his fingertips. Forty-five kids at an area elementary school feel nauseous and dizzy, but what is the cause? The scenarios go on and on…24 hours a day, seven days a week. The calls fly in via a national hot line: 1-800-222-1222. The ever-ready information specialists quickly elicit answers to crucial questions about poisoning, drugs, and animal bites, and make instantaneous, critical judgment calls—sight unseen. A miss in diagnosis could prove fatal.

This is the routine that has been ongoing for 20 years, since Steven Marcus, MD, toxicologist and UMDNJ-New Jersey Medical School (NJMS) professor, became director of the then newly established poison information and education center, part of a network operating nationwide. He staffs the phones with a minimum of three experts, including a physician and a pharmacist or nurse, around-the-clock. Marcus, himself, wears two cell phones and a beeper at all times, and is a walking bank of information on toxicology.

The hot line staff gives callers almost-immediate answers to their questions. Sometimes they send callers to their nearest E.R. and sometimes Marcus meets them there. Sometimes he makes a site visit. Always he’s on high alert. Even when he travels to international conferences or goes on vacation, he’s invariably within reach. One of those cell phones is on a separate network that operates almost anywhere in the world, under any conditions. He is the end stop. What he doesn’t know (and that probably isn’t very much), he does know how to access—or to instruct an information specialist to access—via a toxicology data bank with more than two million entries. "You can’t store everything in your brain," he says, "but you do have to know how to find it quickly."

"Ninety percent routine, 5 percent challenge, 5 percent horror" is how he describes the job. "When the phone rings, you have no idea what’s on the other end and what you’ll have to respond to," Marcus states. The hotline team is always watchful for that 5 percent—what may appear ordinary but is highly unusual. Maybe even contagious.

If it’s that unusual, it could signal trouble with repercussions far beyond one person. Is it an ordinary rash or anthrax? Is the outbreak of intestinal symptoms from food gone bad or food that’s been poisoned? Are the breathing problems from normal air pollution or something more sinister? You get the picture—those rather ordinary folks sitting by the phones have some extraordinary job responsibilities. In our post-9/11 consciousness, they can’t afford to relax on the job. They are our antennae, our watchdogs, ever vigilant for the incipient crisis.

"We are constantly looking for patterns, paying attention to the clues," says Marcus. "We ask ourselves, ‘Should this be happening and should this be happening in New Jersey?’"

It’s no mean feat being a watchdog in a world where danger seems to be lurking around too many corners. Fortunately, Marcus and his team don’t work the beat alone.

Together We Win—Building Bridges

Take Bill Halperin, MD, DrPH, for instance. He’s a man with a mission—to create the Garden State’s first "biodefense school," modeled on the U.S. military’s war colleges and using case-based training methods he learned at the CDC. This school would train a core group of locally based public health workers statewide to be ready to act in a systematic fashion at the first hint of bioterrorism. A grandiose ambition? Not for a moment. He’s well-prepared to found such an enterprise—a physician board-certified in preventive medicine with a doctorate in epidemiology, chair of preventive medicine at NJMS, a public health officer trained in surveillance techniques by the CDC, who started as a CDC epidemic intelligence service officer stationed in Trenton and later became a CDC investigator for 25 years, and a former deputy director of one of its institutes.

"We know right away if a plane hits a building, if a bomb explodes, or even if a chemical weapon is utilized. But a biological attack can be subtle," he says. "Maybe it will be several days until someone actually gets symptoms. It could be a week or longer until physicians detect any kind of unusual pattern. But you don’t want to wait for 50 cases of smallpox to get going. You want to prevent that by identifying the first one quickly."

Halperin says that our ability to deal with bioterrorism is directly linked with our ability to investigate more routine outbreaks and epidemics. "If we can’t handle one, we can’t be effective with the other," he states. He worries that the public health infrastructure is very thin at the local level, a result of decades of under-investment in the people who are the first line in preventing disease.

So began the Thursday night group. Soon after 9/11, Halperin reached out to the city of Newark to see if help was needed with improving preparedness for possible new episodes of bioterrorism. He found an enthusiastic partner in Marcia McGowen, Health Officer for Newark. Soon 15 to 20 people, all interested in biodefense, were coming together.

As most of us were glued to our seats in front of the post-9/11 TV coverage of one shocking event after another, these folks felt called to action. Every Thursday at six they gathered in the City Health Department to eat sandwiches and figure out how to beef up the city’s readiness for a biological attack. They worked through many "What if?" scenarios, and what the group determined was not surprising. We were not at all ready to defend ourselves. What if a case of smallpox came through Newark airport? What if Newark was the target of a dirty bomb? What if anthrax was sent through New Jersey’s postal system again?

The word they came back to again and again was surveillance—alertness, vigilance, "watching over." They surmised that New Jersey needed a better surveillance system to detect problems early, thus minimizing the time between the release of a bioweapon and the first response to it.

"We formulated questions and we came up with some answers. Even more important, we developed first-name, working relationships with each other, and we know who to call in each department," says Halperin, who initially chaired the group. Those meetings, held under the auspices of the City Health Department, were well attended—representatives from all area hospitals, the State Health Department, the city of Newark, the Port Authority, emergency medical transporters and communicators, and poison control experts.

The group had the immediate effect of addressing some obvious weaknesses in surveillance. Its long-term effect has been the building of stronger bridges, especially between New Jersey Medical School and the City Health Department. Halperin glows when talking about one of his junior faculty who is now the city epidemiologist and pivotal in de-veloping a hospital-based, citywide surveillance system.

Halperin is quick to point out that although the impetus for the group’s meeting was the anthrax attacks, everyone stands to gain from the work. Better surveillance for bioterrorism means better surveillance for the more "usual" illnesses such as whooping cough, TB, measles and meningitis, too.

The Thursday night group now meets monthly rather than weekly. But participants are still on high alert. They stand poised for action at the drop of a hat, or something else.

Smallpox—No Small Threat

We used to think smallpox was licked. We used to think smallpox was a nonissue. Now it’s foremost and up front in our brains. We’ve all seen the photos of its ugly face and we never want to see it again.

How can we ensure our safety from what may be the pathogen most dangerous to the human species? Vaccinate, vaccinate, vaccinate. Children? Adults? Only health care workers? Is it safe? Is it prudent? How should we proceed?

These are the questions Tom Denny, MSc, is wrestling with. He launched his first smallpox study with a $30,000 grant from the UMDNJ Foundation to determine if adults older than 30 who have documentation or evidence of a smallpox vaccine retain any immunity. Denny, age 48, tested his own blood as well as that of Jim Oleske, noted pediatric HIV/ AIDS physician, age 58, as part of the pilot group, and both show fairly strong immunological activity. What level of immunity is necessary to mount an effective response to this virus? No one knows that yet.

The NIH has given Denny’s group a $400,000, two-year grant to expand the pilot project. Investigators will study the blood of 150 individuals by decade, age 30 to 40, 40 to 50, and 50 to 60, as well as HIV-infected persons, whose immune systems have been "reconstituted." To date, the study has enrolled 90 participants from the UMDNJ network. Those with an observable scar or documentation but no scar are currently being enrolled. One of the questions being investigated is if a scar indicates greater immunity.

According to Denny, a researcher and director of the Center for Labora-tory Investigation at NJMS, the team will run a battery of assays on each blood sample. Some of these tests are repetitive, but will "protect against false findings." The point of the study is to determine who has a weak response and who has a strong response. "We will measure both T-cell function (indicating memory) and B-cell function (the antibody response). If you have to go to mass vaccination in a hurry and there is a limited amount of vaccine, you should know who needs to be vaccinated immediately and who you could put off," he says.

In the near future, Denny says his team—working with Aventis Pharmaceuticals—may be able to determine which part of the smallpox vaccine triggers a strong immune response. They hope to study this by measuring responses to a panel of 89 peptides that represent parts of the smallpox virus protein. "This will help us to design a new generation of vaccines," he explains.

The current vaccine cannot be given to anyone who is HIV-infected, immune-compromised, or has a skin condition such as eczema or psoriasis. "It’s made with live virus that will replicate and may kill," Denny says. Aventis and others are working on a new vaccine that uses an attenuated (altered) form of the virus.

The smallpox researcher explains that the old vaccine was made by injecting calves with the virus, then scraping cells from the pox on the cow’s skin. "The vaccine was loaded with cow protein," he says. The new vaccines will be grown in tissue culture, and will be more sterile and safer.

Denny’s lab soon expects to receive $6 million over three years from the NIH to serve as the reference lab for new smallpox vaccines. The research-er explains that the material that was used to dilute the vaccinia virus to make smallpox vaccines is no longer any good. Because a new product will be used to dilute the virus, the FDA must test the vaccine all over again.

According to Denny, the NIH will initiate a clinical trial in which 2,000 volunteers will be inoculated with vaccine that uses a new diluting agent. Blood will be drawn before these individuals are given the vaccine, and at two specified times after. (Only those who have previously been vaccinated for smallpox can participate in the trial because there is less risk of bad outcomes.) That blood will be sent to the reference lab at NJMS for testing. "What we hope to see is that the immune response starts low, then gets higher, then higher again," he says. The team will also assess side effects and scars.

If the current vaccine was mandated now for all Americans, Denny believes it could result in 400 to 1,000 deaths. "But data suggests that you could vaccinate three to four days after exposure and although it may not prevent the disease, it would dampen it down. There is a 10 to 15 day incubation period from the time of exposure to when you see disease. You would have some immune response generated before the disease peaks," he says. He explains that past experience suggests that 30 percent of those exposed to the disease and not vaccinated would die.

Of course, in order for this plan to work, you would need to know that you had a case of smallpox somewhere. Then a plan of action drawing rings of response around the sick person would be activated, according to Denny, who is also currently one of seven Robert Wood Johnson Foundation fellows in Washington, DC, studying the issues surrounding healthcare in the U.S.

On the Watch in NJ’s Biggest City

Peter Wenger, MD, is a vaccination specialist. Board certified in infectious disease and pediatrics, he currently serves as the consultant epidemiologist to the Office of Epidemiology and Surveillance in the Newark Department of Health and Human Services as well as being a faculty member in the NJMS Depart-ment of Preventive Medicine. He is dedicated to improving the health of Newark’s children, particularly in raising the immunization rates of preschoolers. What happened post-9/11 didn’t exactly change his job, but it certainly sharpened and broadened his focus and brought his work a little more into the spotlight.

"Public health is about being the eyes, the nervous system, the sensory network for the community," he says. "It’s being aware of the potential of a biological attack, which can be very subtle, and training a cadre of people with the expertise to identify, investigate and report the essential information in a public health emergency."

Wenger sees his role—and that of other public health practitioners—as integral to the success of the Home-land Security effort. The questions participants formulate and wrestle with at the Thursday night sessions in Newark are the same questions that need to be answered at a national level, he says. Among the top issues are communicable disease reporting, quarantine procedures and developing a surveillance system that’s effective in detecting bioterrorism as well as following up on what’s found.

"We don’t expect to have bioterrorist events frequently, hopefully never, but these same surveillance systems are needed to meet the practical needs of everyday life," he explains.

Take an outbreak of pertussis in Newark, for instance. Wenger outlines the broad-brush approach. First you investigate events, identifying the ones that are dangerous, he says. Next, you disseminate vital information to those who need to know it. Then, you intervene.

"This is a complicated process," he says, "and many delicate systems come into play. You have to foster cooperation among many people."

He sees inertia as the biggest obstacle to success. Without an immediate crisis, public health falls to the bottom of the priority list. That’s a lesson straight out of the history books.

When weaponized anthrax traveled through our state in the weeks following 9/11, "we realized we were unprepared to deal with it," he says. "But bioterorism is not new—it’s been used throughout history. It’s a lot cheaper than developing nuclear armaments, so the possibility of facing this again is very, very real. We can’t afford to let inertia creep in. The thing with bioweapons is that once they hit, they persist…they don’t just go away."

Medtower Creates THE Information Source on Biodefense

If knowledge is power—and possibly survival—then Medtower’s newly unveiled biodefense information system, called INFORM, will prove indispensable in educating and preparing New Jerseyans for future bioterrorist attacks. Do you need to know the signs and symptoms of viral hemorrhagic fever? Plague? Tularemia? Need guidelines for a hospital response to botulism? Anthrax? Smallpox? Do you and your co-workers require training in biological or chemical agents? Do you need an immediate update on an imminent threat?

For all these questions, you can now access the Internet-based INFORM system, a comprehensive, validated biodefense information platform for healthcare professionals, emergency frontline-responders and the general public in need of disease risk communication, education, and breaking alerts. INFORM also provides a conduit for communicating with the state’s leading bioterrorism experts, especially in the event of a biological or chemical attack or an infectious disease outbreak.

The system has been jointly developed by UMDNJ’s Center for BioDefense at NJMS (see story by Mary Ann Littell) and Medtower, a private affiliate of UMDNJ that provides information management and communication tools to life science industry, academic institutions and the public.

Real-time, validated information that is easily accessible is the key here. In order to keep users continuously informed, the system disseminates daily updates, breaking news, and almost instantaneous "alerts" and "bulletins."

"The INFORM site is organized for easy navigation," says Neeraj Kumar, CEO of Medtower. "You don’t have to read through reams of extraneous material to locate your topics of interest. For each potential agent of warfare, such as smallpox or mustard gas, INFORM provides information that is relevant and specific to the background of the user. For example, a physician in a hospital may want to access validated information on the epidemiology or pathology of a disease, while a first responder may desire access to more sensitive information such as prevention, response and quarantine plans."

Also planned are educational modules and expert-moderated discussions, where hosts, such as Nancy Connell, PhD, director of the Univer-sity’s Center for BioDefense, will lead forums and training sessions. Qualified participants can also ask questions directly to the relevant bio-defense expert as well as search past archived discussions or seminars.

"We view this as a great opportunity to make a difference to the state," says Kumar.

Building a biodefense information system—like the other critical steps to ensure the safety of New Jerseyans—is choreographed to move the state way ahead of the curve.