Pretty cool article. Scientist love, stock has been awful :-)
Imaging technology sheds new light on diseases
By Scott Kirsner | April 11, 2005
Like a magician performing a polished trick, only with much less patter, Kai Tao places a small white mouse into a tall gray machine that resembles a refrigerator with an odd dome on top. Tao, a research associate at Tufts University School of Medicine in Boston, sets the animal down belly first onto a shelf inside the machine, in the middle of a square target painted by a green laser. The animal is alive, but he has been rendered motionless by an anesthetic.
Sixty seconds later, an image of the mouse pops up on Tao's computer screen. Tao and Gary Sahagian, a Tufts professor who studies the way cancer spreads, examine the spectrum of colors -- turquoise and red and green -- that appear throughout the mouse's body, like bright bubbles. The bubbles are indicators of where tumors are beginning to grow in the mouse's body -- in one lung, the femur, and possibly part of the intestine.
This $300,000 machine, made by Xenogen Corp., a California company, is part of a new wave of imaging technology that's giving academic researchers like Sahagian and Tao, as well as drug companies like Merck, Millennium, Novartis, and Vertex, a way to actually see diseases as they unfold in a living animal -- and determine whether newly discovered drugs will be effective weapons against them.
It's a glimpse into diseases and infections that scientists haven't had before. (The technology has already contributed to the FDA approval of a powerful antibiotic from Lexington-based Cubist Pharmaceuticals.) It can reduce the number of lab animals sacrificed over the course of a given experiment. (Fewer mice get scanned more often, rather than lots of mice being dissected to see what's happening inside.)
And the way the Xenogen system works is fascinating. A gene derived from the firefly, called luciferase, is inserted into cells of the lab animal so that they glow in the dark. While the glowing cells inside the mouse wouldn't be visible to the human eye, like fireflies on a summer night, the inside of Tao's magical box is outfitted with a light-sensitive camera that can create a picture of what's happening inside the animal, based on the light its cells are emitting.
The hope, as with most new big-ticket tools that universities and corporations purchase for their labs, is that the Xenogen machine will offer a more sophisticated understanding of disease, lead to drugs that are safer and more effective for humans, and reduce drug development costs -- all while speeding up the process. Of course, it's usually difficult to gauge the impact of a single machine.
Xenogen president Pamela Contag began laying the groundwork for the company in the early 1990s, while she was studying at Stanford University the way pathogens interacted with their host organisms. She noticed that experiments done in a Petri dish often played out very differently when done in a living animal. While coordinating a course during the summer of 1992 at the Woods Hole Oceanographic Institute on Cape Cod, she talked with a scientist there who had been working with luciferase -- and began thinking about using the glow-in-the-dark gene to tag the pathogens she was studying, allowing her to observe as they migrated and multiplied in a living animal.
Xenogen went public in 2004, and last year the company sold more than 80 of its Ivis Imaging Systems, which range in price from $150,000 to $300,000. (Competitors in the field, which is known technically as ''in vivo biophotonic imaging," include Kodak, AntiCancer of San Diego, and Germany's Berthold Technologies.) ''It's ramping up quite quickly for an instrument business," says Contag. She spoke to me by phone last week from Logan Airport; she'd been in town visiting customers.
Boston companies and academic labs were among the earliest adopters of Xenogen's technology. Cubist Pharmaceuticals tagged bacteria with the luciferase, and then tracked whether a drug the company was developing, Cubicin, was effective in killing off the bacteria in mice. ''If the bacteria are dead, they no longer luminesce," says Jeff Alder, vice president of drug discovery and evaluation at Cubist. ''We'd see red in the areas of most intense infection," but the color would disappear to indicate that the treatment was working.
''This allows us to collect much more data," Alder continues. ''We can get hourly cuts on how the infection is progressing. It's kind of like an X-ray or an MRI, but those aren't able to show bacteria." Alder says that Cubist was the first company to use imagery from the Xenogen system in filing with the FDA to get Cubicin approved. Now, the company is using the system to study drugs that may combat meningitis and bacterial endocarditis, an infection of the heart.
At Millennium Pharmaceuticals in Cambridge, Mark Rolfe, the senior director of oncology discovery, says that the new imaging technology allows researchers there to get information from the same lab animal over a longer period of time, rather than continually having to euthanize and dissect an animal in order to compare the progress of its cancer to a different animal dissected earlier. ''You can see how new compounds work in the same animal over time," Rolfe says. ''If I were setting up a study 15 years ago, I'd have needed hundreds of mice, and I would have had to sacrifice them on a time course."
At the Dana-Farber Cancer Institute, Andrew Kung talks about using the Xenogen technology for a kind of target practice; imagine throwing rocks at a neon sign in the dark, and you'll get the idea. ''Many breast cancer cells depend on estrogen," Kung says. ''If you make a breast cancer cell that glows when estrogen is present, and you implant that into a mouse, what you can do is test different compounds to see if they block estrogen in cancer cells." The end result could be a drug that starves breast cancer cells.
Many scientists, like techies of all stripes, like to have access to the latest toys in order to be perceived as being on the leading edge -- and to make their counterparts jealous.
But Kung says there's more to the new generation of imaging technology. ''For us, it isn't just a matter of pretty pictures and new toys," he says. ''This is a simple technology that can show us what's happening on a molecular level in real time, and it really does help us reduce the number of animals we use. It has also allowed us to do experiments that were otherwise not possible."
Breakthrough science can sometimes seem like magic.
Scott Kirsner is a contributing editor at Fast Company. He can be reached at skirsner@verizon.net. |
