One in three people worldwide is infected with tuberculosis, mostly in developing nations where malnutrition, poverty and HIV increase the likelihood that a dormant infection will grow into a deadly disease. To make matters worse, many TB strains are now resistant to antibiotics. TB would probably not develop resistance against a vaccine, so the race is on to find one. Colorado State University is helping this effort, by testing TB vaccines from around the world. Shelley Schlender visited the school's state-of-the-art biohazard lab in Fort Collins, Colorado.
Stainless steel counters and giant freezers fill Ian Orme's lab. He opens one of the freezers to show samples of drugs and genetic material. "We've been doing a lot of things with DNA and RNA, so there's lots of different very caustic agents for doing certain things," he says.
Professor Orme's assistants handle tiny Petri dishes beneath a ventilation hood. "We're pouring plates for culturing microbacteria," says one of them.
The workers wear surgical masks and latex gloves. While such precautions are wise at any lab, this micro-biologist says they're essential when the subject is tuberculosis.
"This is the number one disease in the world," he said. "I hate to say this, but it's out of control. It's out of control in South Africa. It's out of control in India and China and the Far East. If you're sitting on a jet plane leaving New Delhi, and someone behind you is coughing, it isn't a joke."
TB can lie dormant in a healthy person's lungs for a lifetime. But malnutrition, untreated HIV and other assaults on the body give TB a chance to multiply. Then, as Ian Orme explains, each time that individual sneezes or coughs, tiny water droplets of infection spread through the air.
"The main symptom of TB, obviously, is coughing up sputum that is just completely loaded with the bacterium," he said. "If you've got 10 people living in a room, and the person has TB, the rest of them are going to catch it."
To fight back, scientists at Colorado State University study research animals that have been infected with TB. Some experiments are more dangerous than others. So, in addition to this Level 1 security lab, Professor Orme directs a 1,000 square meter, Level 3 biohazard lab, where he says, most of the 'nasty things' are handled. The building is surrounded by a barbed wire fence.
"You can look at it from the outside, but you can't go inside," said Paul Morley, a biosecurity officer at the university. "There are regulations as to who can go inside. They have to have appropriate levels of training."
Those with proper training still wear lots of safety gear.
"We use scrubs similar to what they'd use in an operating room," points out Rob Christiansen who works with guinea pigs inside the biohazard lab. "We wear respirators that filter all the air that you're breathing in, hairnets and clogs."
People must shower before entering or leaving the biohazard lab. And Professor Orme says even the building incorporates safety measures just in case a beaker of live TB bacteria is ever dropped or broken. "Every room in there is under intense negative air, so if the bacterium is released into the environment in a room there, it would instantly be sucked up into a very sophisticated filter system which would never allow it to get out," he said.
One reason for the strict procedures is Ian Orme's testing method. Most researchers study TB by injecting the bacteria into the bloodstream of their laboratory animals. While this provides many clues about TB, the infection doesn't mimic the human disease. So Professor Orme infects his lab animals by spraying them with a TB mist.
"This is how people catch TB," he said. "They breathe them into the lungs. That's the basis of our model, and it's the basis of our philosophy here, to try and be as realistic as possible."
Worldwide, he notes, few labs use this technique. "It's not for beginners," he said. "This is a very dangerous thing, and obviously you have to have the facilities to contain it, you have to know what you're doing with it, and you have to take stringent safety precautions."
But he considers it worth the risk, because it can reveal dangerous side effects that other techniques may miss. For example, one vaccine showed great promise in another lab - it killed the TB bacteria without harming the mice. So the researchers asked Professor Orme to try it on his mice.
"And when we tested this vaccine under these conditions, it was, um, fatal, not to put too fine a word on it," he recalled.
But other vaccines have shown great promise. The Colorado State University scientist highlights one of them by showing a photograph of lung tissue ravaged by TB. It was taken before a new post-exposure vaccine was injected into sick guinea pigs. A second photograph, taken two years later, shows the animals' lung tissue healthy again. Ian Orme says it's the first time he's seen a vaccine that reversed TB damage in an animal. He hopes for similar results someday in human beings.
"We don't know how many of those are going to work, but certainly I think some of them will, and so I think we can definitely improve vaccination against TB in the next fifty years," he says. "And I think a combination of vaccination in the long term and chemotherapy for the shorter term, we could make very considerable inroads into this really horrible disease."
Thanks to a grant from the National Institute of Allergy and Infectious Diseases, research centers around the world can send their experimental TB vaccines to Colorado State University, free of charge, for testing. To date, Ian Orme and his team have received over 100 samples.
