Chicago Tribune - January 4, 2003
Jon Van
For the past few years, Hope and McDonald have told colleagues they can watch viruses as they move around inside a living human cell.
That seemed an outrageous claim to people schooled to believe it's impossible to see such tiny things.
"When we'd go to scientific meetings to describe our work, they'd usually schedule us for the end of a session," said Hope, "because they knew there'd be a lot of disagreement and it could just spill into the break instead of delaying the next presentation."
But in the last few months, the two Illinois researchers have gained enough credibility that colleagues no longer scoff.
They've made computer-generated moving images that show how the human immunodeficiency virus that causes AIDS can migrate through a human cell toward the cell's nucleus, where it takes over genetic material to infect more cells.
"We follow Yogi Berra's philosophy that `You can see a lot just by lookin','" said McDonald. "No one had any idea how individual viruses act inside a cell, so being able to watch them tells you a lot."
The reason most experts didn't think it possible to look at a virus within a living cell is that viruses are so tiny, they're smaller than the waves of visible light used to illuminate them. Even with the world's best optical microscopes, it's not possible to see something that's smaller than a light wave.
So to look at viruses, scientists usually use microscopes that employ electrons instead of light waves to illuminate their subjects. But electron microscopes require their targets be sliced and prepared in special ways before they're ready for view, and that means death to a living cell.
To overcome the optical microscopy shortcomings, the researchers inserted a molecule into HIV that glows green when hit by blue light.
This molecule, extracted from jellyfish, means that even though it's not possible to look directly at the virus, you can see its green glow as it moves around within a cell.
McDonald and Hope used other molecular agents to illuminate portions of the cell's infrastructure and found there's a transportation system within human cells that a virus can use to get itself around.
Think of a single human cell as if it were greater Chicago. A lot of visitors who come into the area at the edges might wander around near Aurora, Dolton and Zion, never finding their way to State and Madison in Chicago. But if some of those strangers happened to get on Metra trains, they'd zip downtown rather quickly.
That's more or less how HIV is able to infect a human cell.
The work at UIC suggests the virus is far more infectious than scientists previously believed.
To convince colleagues their light show was authentic, the researchers froze some cells after making images, then produced electron microscopic images to confirm it was the real deal.
While the concept is fairly straightforward, doing the work demands about as much skill as playing a concert piano.
McDonald, for example, had to give up coffee for months so that his hands would be steady enough to do the fine work.
Training cadres of workers to do all the work needed to use the technology to its fullest extent will be a real challenge, said Hope, who hopes next to learn more about how the deadly Ebola virus works.
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