A Man with an Overseas Mission
by Maryann Brinley

ook at the screensaver on David Perlin’s laptop. The president and scientific director of the Public Health Research Institute (PHRI) at the International Center for Public Health — the newest center at UMDNJ - New Jersey Medical School (NJMS) — has a backdrop photo to remind him of “what we have to worry about and the challenges we face.

“This is in China,” he explains pointing to the computer screen. “It’s from one of those live animal markets in Shanghai and this woman was not happy I was taking her picture.”

His photo is foreign and dramatic but, like a litmus test which suddenly comes up positive, the shot is perfectly suited to its present situation. It puts Perlin both here as well as there in China. As head of PHRI, an institution which is celebrating 65 years of its research, he helps guide world-renowned specialists who are determined to have an impact on infectious diseases — some of which have been around for centuries, like tuberculosis, and some of which may be brand new to the world, like the current strain of bird flu, H5N1, bearing down on the U.S.

“I know it sounds trite but it’s true,” Perlin says, “we’re in this business because we think we can make a difference.”

Before he can click any icon on his computer linking him to a nearly endless to-do list of local, national and international infectious disease projects, this man looks at cages of chickens, ducks, and pigeons. “They were all pretty sick,” are his recollections of the birds. There they are, possibly infected with an avian influenza virus, on the dirt in front of an irritated vendor. In the photo, her eyes are warning him away but Perlin has captured the everyday clutter of her life, including pots for cooking and other living essentials, sitting in close proximity to the inherent danger in her sickened merchandise. A bike leans against a customer.

“It’s not only the large chicken farms that we have to worry about,” explains this outspoken scientist with opinions on everything from the avian flu to bio-weapons of mass destruction, plague, ebola, West Nile virus, tuberculosis, HIV/AIDS, hepatitis, malaria, anthrax and opportunistic fungi. What concerns Perlin are the marketplaces like the one in his photo and “the small backyard farms where animals are not always healthy and children, in particular, are handling them.”

Yet, his computer image not only reminds him of the threat of infectious disease in a world that has grown smaller than ever, but also that this woman is a human being whose birds are her livelihood. “They are a source of food and income. No matter how sophisticated we get in the laboratory, in the end, we have to remember that it’s people like her who can impact the rest of us. She’s just making a living, trying to get through life. Yet, she could easily become a disease vector.” Perlin believes that an effective vaccine and better methods to manufacture vaccines should be top public health priorities. Stockpiling drugs like Tamiflu, which may only be effective when used early, is not the answer.

An authority on drug-resistant fungal infections and the rapid diagnosis of bloodstream and respiratory pathogens, Perlin began his PHRI career in 1985 and is currently an NJMS professor of microbiology and molecular genetics. A graduate of Cornell, Yale and Rochester, when he was looking for a position in the New York City area, he realized, “The research environment at PHRI has always been exceptional.” Created at the emergence of the antibiotic era to address problems like polio, smallpox, typhoid fever and other infectious diseases, PHRI has been “a breeding ground for outstanding scientists, including several National Academy of Sciences members and one who went on to win a Nobel Prize. We have a rich history of joining science with medicine which forces you to ask yourself all the time: where can I make a difference?”

Perlin himself has experienced what he calls “a real evolution as a scientist,” starting off as a biochemist interested in the structures of molecules involved in bio-energetics. While his range of interests expanded significantly after he became scientific director in 1992 and then president in 2005, his PHRI lab focuses on the mechanisms of antifungal drug resistance, an area critical for cancer and HIV/AIDS, and new methods to rapidly detect disease-causing organisms in immune-compromised patients. He wants to understand pathogens, how the body responds to them and how they respond to the body, adapting, evolving and becoming resistant to therapy.

“One of the most exciting things for me has been to create opportunities and new paths for PHRI scientists. When I became scientific director, we had no TB work going on here.” Then, Barry Kreiswirth, PhD, started doing “DNA fingerprinting because of a massive outbreak of multi-drug-resistant TB in New York City, something we had never seen before.” Soon, scientists like Issar Smith, PhD, Karl Drlica, PhD, and Marila Gennaro, MD, were pursuing TB questions. From initial studies, six National Institutes of Health (NIH) grants resulted and eight PHRI laboratories currently focus on TB, generating more than $50 million in research funds in the past decade.

Clinical and epidemiological studies with TB patients in Russia, South Africa, China and elsewhere have been essential. “This is an age-old bug that grows slowly but kills several million people a year. You can’t just do basic science or use a model system if you want to change the course of a disease that has been around for centuries. It requires an acute understanding of the disease in humans. Our TB program is broad in scope and involves everything from fundamental research which asks why these organisms cause disease, all the way through diagnostics and epidemiology.” Even the Centers for Disease Control and Prevention (CDC) relies on PHRI to do molecular typing for the metropolitan area and Kreiswirth’s epidemiological group has fingerprinted 21,000 strains worldwide.

PHRI scientists are studying host and genetic factors in TB, new classes of drugs, as well as drug resistance and blood testing. The shift to tuberculosis research work was also a factor in luring PHRI, a New York City institution, to their new headquarters in Newark’s Science Park in 2002, where the group has been able to join forces with the NJMS Global Tuberculosis Institute at UMDNJ. In March, PHRI also became part of NJMS — an institutional marriage Perlin is very proud to have helped engineer.

Since the September 11th terrorists’ attack on the World Trade Center in 2001 and the subsequent anthrax scare, this director finds himself in the media spotlight, consulting on Capitol Hill and on the world stage, speaking, writing and advising the public, government agencies and politicians about infectious diseases. Not shy about sharing his beliefs, he’s become a frequent contributor to The New York Times Op-Ed page writing on topics as wide-ranging as hospital infections, AIDS prevention, smallpox vaccination, lessons learned from the anthrax crisis, and “Bio-terror’s New Frontier.” Always a hands-on scientist, he was there consulting on the clean-up of the anthrax-contaminated postal distribution center in Hamilton Township in 2003.

A member of the New York City Department of Health advisory panel on Biodefense, the New York Academy of Sciences Emerging Infectious Disease Discussion Group and the Executive Committee of the Northeast Biodefense Center, he says, “What’s really gratifying is that we are getting people’s attention.” Among his publication credits is his co-authorship of The Complete Idiot’s Guide to Dangerous Diseases and Epidemics. “I’m always looking for ways to help further the national research agenda and to educate the public on the challenges of infectious diseases. Our concern cannot just be local, it must extend globally.”

To underscore how easily a distant bug can rapidly have global impact, Perlin recalls the encounter that brought the public health problems of China to his attention. It was during the height of the 2003 SARS crisis, an epidemic of severe acute respiratory syndrome which began in China, killed 813 people worldwide and isolated the Canadian city of Toronto.

“I got a call from the Chinese consulate in New York one morning in February 2003,” he says. A woman, the vice consul, was desperate to meet with him. She had been referred by the New York City Department of Health and Perlin told her he would be happy to consult but he was leaving that afternoon for Europe. Could they arrange a time during the following week when he returned?

“No,” she told him. “We’ll be there right away.”

Within the hour, a large contingency of Chinese officials, all male except for the female vice consul, were in Perlin’s second floor office in Newark.

“They were scared,” he remembers, as well as forthcoming about their problems.

SARS was spreading and “they needed the molecular beacon technology we developed at PHRI.” In China, feverish patients with atypical pneumonia, possibly signaling SARS or another infectious disease, were wandering into hospitals, but before a diagnosis could be rendered, they were leaving without proper treatment or enough information to warrant being quarantined. The possibility of these undiagnosed cases of infection spreading to others was grave. More than 8,000 people worldwide would eventually become sick with SARS.

The Chinese government “was desperate for the faster diagnostics,” Perlin says. And they had come to the right place.

Molecular beacons, hairpin-shaped probes, can light up and detect the presence of specific nucleic acid targets. They were invented and patented by two PHRI scientists, Fred Kramer, PhD, and Sanjay Tyagi, PhD, and have been licensed worldwide to more than 45 different companies. There is even more future potential, according to Perlin. “The beacons are phenomenal and of enormous value because many large diagnostic companies have switched their manufacturing platforms to incorporate them. With applications for science and medicine, as well as research and commercial use, these simple tools can rapidly pick up the presence of a viral infection or a bio-weapon like anthrax in the blood or tissue of a victim.”

The Chinese government was so pleased with PHRI’s willingness to help that three collaborative projects are now ongoing. “We’ve been treated royally on our visits with banquets, tours of the Forbidden City and genuine openness,” says Perlin, who has traveled to the Far East several times since that first phone call. “China has 1.4 million new cases of TB each year resulting in 250,000 deaths,” he explains.

Working with a pulmonary group at Peking Union Medical Center Hospital (PUMCH) — the most prestigious hospital in China founded by the Rockefeller Foundation in the 1920s — PHRI is attempting to compare data from China’s epidemic to information about drug resistant TB in Africa, India, Russia and South America. “We can learn about the similarities and differences that contribute to this global plague.”
In a second Chinese project, a PHRI team wants to put molecular beacon diagnostic technology in all large urban Chinese hospitals. Clinicians at PUMCH in Beijing have already received training with the probes to identify outbreaks of bacterial, fungal and certain viral infections. “We’re also introducing the technology to various other groups in Shanghai.” Patients will be diagnosed within two to four hours in a PUMCH pilot program, faster than nearly all hospitals here in the U.S., according to Perlin.

A third venture has Perlin and Kreiswith developing treatments for TB, HIV and hepatitis B with Dr. Jian-Don Jiang, Director of the Institute for Medicinal Biotechnology through the Chinese Academy of Medical Sciences, and also a professor at Mount Sinai for six months each year. “Many of the top Chinese professionals here in the U.S. are recruited like this to work half time back in China. We met, we talked, we put together a game plan and it was one of the few in the world to win a Gates Global Challenge Fund grant last year.”

The researchers are building on a classic strategy of Chinese medicine called “Wei Qi” or “protection from inside,” and targeting components of human cells to try to stop organisms from developing drug-resistant strains. Winning the grant from the Bill and Melinda Gates Foundation was a real coup because the team was up against stiff competition from 75 countries, Nobel laureate investigators, prominent academics and the best and brightest from biotechnology companies and government research institutions. “This was really nice. It’s pushing us forward into new areas.”

Operating out on the cutting edge of medical research, “like a high wire act with no net,” he says, is perfectly natural for Perlin and his PHRI colleagues. After all, this is a scientist who lives by the rule, “If you become too complacent, too relaxed, it won’t take long for you to fall behind.” And you can’t fall behind when the challenges posed by infectious diseases are so monumental.